29 results on '"Faragó N"'
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2. Hasznos rítusok és haszontalan technikák. A rituális cselekvés régészeti azonosításának néhány elméleti kérdése egy pattintott kő leletegyüttes kapcsán. (Useful Rites and Unfit Techniques. Thoughts about archaeological perception of ritual.)
- Author
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Király, A., Faragó, N., Mester, Zs., Histoire naturelle de l'Homme préhistorique (HNHP), Muséum national d'Histoire naturelle (MNHN)-Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), and Eötvös Loránd University, Institute of Archaeological Sciences
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[SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory - Abstract
International audience; How can we observe specific material correlates of ritual practice with respect to other activities? Our essay relates this question to the difficulties surrounding the definition of ritual. We argue that the category of ritual practice is acknowledged by the researcher, thus consequent, all-encompassing criteria can not be defined for its recognition in the archaeological record. Nevertheless, systematic study of past actions is possible with the help of sequential methods like the chaîne opératoire. Through our case study, a Neolithic blade depot from Boldogkőváralja, we find that built on proper analytic methods, „ritual” can be a powerful heuristic device during the interpretive phase of a research cycle.
- Published
- 2020
3. Houses, Households, Activity Zones in the Post-LBK World. Results of the Raw Material Analysis of the Chipped Stone Tools at Polgár- Csőszhalom, Northeast Hungary
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Faragó Norbert
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Late Neolithic ,chipped stone tools ,household archaeology ,intra-site archaeology ,spatial analysis ,Archaeology ,CC1-960 - Abstract
In the last few decades, archaeological research has invested more energy into better understanding of past societies than ever before. There are several different factors that have made these changes possible. The development of non-destructive investigating techniques has made it possible to choose more precisely where to collect new data. Furthermore, advances in information technologies and the natural sciences have provided new tools to analyze and evaluate the data. Our project started in 2012 in order to evaluate the enormous amount of archaeological material excavated at Polgár-Csőszhalom, the most significant site of the post-LBK period in North-East Hungary. Our main motivation was to reconstruct the community of this complex site with the application of multilevel statistical methods and spatial information technologies. The investigation of raw material from the chipped stone industry yielded sixteen different activity zones on the flat settlement. The differentiation of these zones was possible through the recognition of the repeated patterns of the raw materials used. The analyses show that whilst individual households, as the elementary building modules of the settlement community, were self-sufficient in tool making, the procurement of raw materials seems to have been communal. The homogenous picture apparent from the distribution of the local raw materials and the lack of accumulation from more distant sources suggest conformity at household level.
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- 2016
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4. MicroRNA profile of polyunsaturated fatty acid treated glioma cells reveal apoptosis-specific expression changes
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Das Undurti N, Fehér Liliána Z, Kitajka Klára, Faragó Nóra, and Puskás László G
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PUFA ,micro RNA ,glioblastoma ,apoptosis ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract Background Polyunsaturated fatty acids (PUFAs) such as γ-linolenic acid (GLA), arachidonic acid (AA) and docosahexaenoic acid (DHA) have cytotoxic action on glioma cells. Results We evaluated the cytotoxic action of GLA, AA and DHA on glioma cells with specific reference to the expression of miRNAs. Relative expression of miRNAs were assessed by using high throughput nanocapillary real-time PCR. Most of the miRNA target genes that showed altered expression could be classified as apoptotic genes and were up-regulated by PUFA or temozolomide treatment, while similar treatments resulted in repression of the corresponding mRNAs, such as cox2, irs1, irs2, ccnd1, itgb3, bcl2, sirt1, tp53inp1 and k-ras. Conclusions Our results highlight involvement of miRNAs in the induction of apoptosis in glioma cells by fatty acids and temozolomide.
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- 2011
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5. Levelek egy aprófaluból 1989
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Faragó Nándor and Kovács Katalin
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History (General) and history of Europe ,Economic history and conditions ,HC10-1085 ,Economic growth, development, planning ,HD72-88 ,Sociology (General) ,HM401-1281 ,International relations ,JZ2-6530 - Published
- 1990
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6. Cardioprotective microRNAs (protectomiRs) in a pig model of acute myocardial infarction and cardioprotection by ischaemic conditioning: MiR-450a.
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Nagy RN, Makkos A, Baranyai T, Giricz Z, Szabó M, Kravcsenko-Kiss B, Bereczki Z, Ágg B, Puskás LG, Faragó N, Schulz R, Gyöngyösi M, Lukovic D, Varga ZV, Görbe A, and Ferdinandy P
- Abstract
Background and Purpose: Cardioprotective miRNAs (protectomiRs) are promising therapeutic tools. Here, we aimed to identify protectomiRs in a translational porcine model of acute myocardial infarction (AMI) and to validate their cardiocytoprotective effect., Experimental Approach: ProtectomiR candidates were selected after systematic analysis of miRNA expression changes in cardiac tissue samples from a closed-chest AMI model in pigs subjected to sham operation, AMI and ischaemic preconditioning, postconditioning or remote preconditioning, respectively. Cross-species orthologue protectomiR candidates were validated in simulated ischaemia-reperfusion injury (sI/R) model of isolated rat ocardiomyocytes and in human AC16 cells as well. For miR-450a, we performed target prediction and analysed the potential mechanisms of action by GO enrichment and KEGG pathway analysis., Key Results: Out of the 220 detected miRNAs, four were up-regulated and 10 were down-regulated due to all three conditionings versus AMI. MiR-450a and miR-451 mimics at 25 nM were protective in rat cardiomyocytes, and miR-450a showed protection in human cardiomyocytes as well. MiR-450a has 3987 predicted mRNA targets in pigs, 4279 in rats and 8328 in humans. Of these, 607 genes are expressed in all three species. A total of 421 common enriched GO terms were identified in all three species, whereas KEGG pathway analysis revealed 13 common pathways., Conclusion and Implications: This is the first demonstration that miR-450a is associated with cardioprotection by ischaemic conditioning in a clinically relevant porcine model and shows cardiocytoprotective effect in human cardiomyocytes, making it a promising drug candidate. The mechanism of action of miR-450a involves multiple cardioprotective pathways., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
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- 2024
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7. A Novel 2-Methoxyestradiol Derivative: Disrupting Mitosis Inhibiting Cell Motility and Inducing Apoptosis in HeLa Cells In Vitro.
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Njangiru IK, Bózsity-Faragó N, Resch VE, Paragi G, Frank É, Balogh GT, Zupkó I, and Minorics R
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The clinical application of 2-methoxyestradiol (2ME) in cancer therapy has been limited by its low solubility and rapid metabolism. Derivatives of 2ME have been synthesised to enhance bioavailability and decrease hepatic metabolism. Compound 4a , an analog of 2ME, has demonstrated exceptional pharmacological activity, in addition to promising pharmacokinetic profile. Our study, therefore, aimed at exploring the anticancer effects of 4a on the cervical cancer cell line, HeLa. Compound 4a exhibited a significant and dose-dependent antimetastatic and antiinvasive impact on HeLa cells, as determined by wound-healing and Boyden chamber assays, respectively. Hoechst/Propidium iodide (HOPI) double staining showcased a substantial induction of apoptosis via 4a , with minimal necrotic effect. Flow cytometry revealed a significant G2/M phase arrest, accompanied by a noteworthy rise in the sub-G1 cell population, indicating apoptosis, 18 h post-treatment. Moreover, a cell-independent tubulin polymerisation assay illustrated compound 4a 's ability to stabilise microtubules by promoting tubulin polymerisation. Molecular modelling experiments depicted that 4a interacts with the colchicine-binding site, nestled between the α and β tubulin dimers. Furthermore, 4a displayed an affinity for binding to and activating ER-α, as demonstrated by the luciferase reporter assay. These findings underscore the potential of 4a in inhibiting HPV18+ cervical cancer proliferation and cellular motility.
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- 2024
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8. Network of large pedigrees reveals social practices of Avar communities.
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Gnecchi-Ruscone GA, Rácz Z, Samu L, Szeniczey T, Faragó N, Knipper C, Friedrich R, Zlámalová D, Traverso L, Liccardo S, Wabnitz S, Popli D, Wang K, Radzeviciute R, Gulyás B, Koncz I, Balogh C, Lezsák GM, Mácsai V, Bunbury MME, Spekker O, le Roux P, Szécsényi-Nagy A, Mende BG, Colleran H, Hajdu T, Geary P, Pohl W, Vida T, Krause J, and Hofmanová Z
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- Adult, Female, Humans, Male, Asia ethnology, Cemeteries history, Consanguinity, Europe ethnology, Genomics, History, Medieval, Politics, Adolescent, Young Adult, Archaeology methods, DNA, Ancient analysis, Family Characteristics ethnology, Family Characteristics history, Grassland, Pedigree
- Abstract
From AD 567-568, at the onset of the Avar period, populations from the Eurasian Steppe settled in the Carpathian Basin for approximately 250 years
1 . Extensive sampling for archaeogenomics (424 individuals) and isotopes, combined with archaeological, anthropological and historical contextualization of four Avar-period cemeteries, allowed for a detailed description of the genomic structure of these communities and their kinship and social practices. We present a set of large pedigrees, reconstructed using ancient DNA, spanning nine generations and comprising around 300 individuals. We uncover a strict patrilineal kinship system, in which patrilocality and female exogamy were the norm and multiple reproductive partnering and levirate unions were common. The absence of consanguinity indicates that this society maintained a detailed memory of ancestry over generations. These kinship practices correspond with previous evidence from historical sources and anthropological research on Eurasian Steppe societies2 . Network analyses of identity-by-descent DNA connections suggest that social cohesion between communities was maintained via female exogamy. Finally, despite the absence of major ancestry shifts, the level of resolution of our analyses allowed us to detect genetic discontinuity caused by the replacement of a community at one of the sites. This was paralleled with changes in the archaeological record and was probably a result of local political realignment., (© 2024. The Author(s).)- Published
- 2024
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9. Surface Modification of Titanate Nanotubes with a Carboxylic Arm for Further Functionalization Intended to Pharmaceutical Applications.
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Saker R, Jójárt-Laczkovich O, Regdon G Jr, Takács T, Szenti I, Bózsity-Faragó N, Zupkó I, and Sovány T
- Abstract
Nanotechnology is playing a significant role in modern life with tremendous potential and promising results in almost every domain, especially the pharmaceutical one. The impressive performance of nanomaterials is shaping the future of science and revolutionizing the traditional concepts of industry and research. Titanate nanotubes (TNTs) are one of these novel entities that became an appropriate choice to apply in several platforms due to their remarkable properties such as preparation simplicity, high stability, good biocompatibility, affordability and low toxicity. Surface modification of these nanotubes is also promoting their superior characters and contributing more to the enhancement of their performance. In this research work, an attempt was made to functionalize the surface of titanate nanotubes with carboxylic groups to increase their surface reactivity and widen the possibility of bonding different molecules that could not be bonded directly. Three carboxylic acids were investigated (trichloroacetic acid, citric acid and acrylic acid), and the prepared composites were examined using FT-IR and Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The toxicity of these functionalized TNTs was also investigated using adherent cancer cell lines and fibroblasts to determine their safety profile and to draw the basic lines for their intended future application. Based on the experimental results, acrylic acid could be the suitable choice for permanent surface modification with multiple carboxylic groups due to its possibility to be polymerized, thus presenting the opportunity to link additional molecules of interest such as polyethylene glycol (PEG) and/or other molecules at the same time.
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- 2023
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10. Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata .
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Kovács T, Lajter I, Kúsz N, Schelz Z, Bózsity-Faragó N, Borbás A, Zupkó I, Krupitza G, Frisch R, Hohmann J, Vasas A, and Mándi A
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- Humans, Molecular Structure, Magnetic Resonance Spectroscopy, Magnetic Resonance Imaging, Asteraceae chemistry, Sesquiterpenes pharmacology
- Abstract
A new flexible germacranolide ( 1 , lobatolide H) was isolated from the aerial parts of Neurolaena lobata . The structure elucidation was performed by classical NMR experiments and DFT NMR calculations. Altogether, 80 theoretical level combinations with existing
13 C NMR scaling factors were tested, and the best performing ones were applied on 1 .1 H and13 C NMR scaling factors were also developed for two combinations utilizing known exomethylene containing derivatives, and the results were complemented by homonuclear coupling constant ( JHH ) and TDDFT-ECD calculations to elucidate the stereochemistry of 1 . Lobatolide H possessed remarkable antiproliferative activity against human cervical tumor cell lines with different HPV status (SiHa and C33A), induced cell cycle disturbance and exhibited a substantial antimigratory effect in SiHa cells.- Published
- 2023
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11. Crosstalk between the redox signalling and the detoxification: GSTs under redox control?
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Gallé Á, Bela K, Hajnal Á, Faragó N, Horváth E, Horváth M, Puskás L, and Csiszár J
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- Antioxidants, Glutathione metabolism, Oxidation-Reduction, Oxidative Stress, Salicylic Acid, Hydrogen Peroxide, Solanum lycopersicum metabolism
- Abstract
Reactive oxygen species (ROS), antioxidants and their reduction-oxidation (redox) states all contribute to the redox homeostasis, but glutathione is considered to be the master regulator of it. We aimed to understand the relationship between the redox potential and the diverse glutathione transferase (GST) enzyme family by comparing the stress responses of two tomato cultivars (Solanum lycopersicum 'Moneymaker' and 'Ailsa Craig'). Four-week-old plants were treated by two concentrations of mannitol, NaCl and salicylic acid. The lower H
2 O2 and malondialdehyde contents indicated higher stress tolerance of 'Moneymaker'. The redox status of roots was characterized by measuring the reduced and oxidized form of ascorbate and glutathione spectrophotometrically after 24 h. The redox potential of 'Ailsa Craig' was more oxidized compared to 'Moneymaker' even under control conditions and became more positive due to treatments. High-throughput quantitative real-time PCR revealed that besides overall higher expression levels, SlGSTs were activated more efficiently in 'Moneymaker' due to stresses, resulting in generally higher GST and glutathione peroxidase activities compared to 'Ailsa Craig'. The expression level of SlGSTs correlated differently, however Pearson's correlation analysis showed usually strong positive correlation between SlGST transcription and glutathione redox potential. The possible redox regulation of SlGST expressions was discussed., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)- Published
- 2021
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12. Automatic deep learning-driven label-free image-guided patch clamp system.
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Koos K, Oláh G, Balassa T, Mihut N, Rózsa M, Ozsvár A, Tasnadi E, Barzó P, Faragó N, Puskás L, Molnár G, Molnár J, Tamás G, and Horvath P
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- Adult, Aged, Animals, Automation, Brain cytology, Electrophysiology, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Neurons chemistry, Patch-Clamp Techniques, Rats, Rats, Wistar, Software, Video Recording, Deep Learning, Neurons cytology
- Abstract
Patch clamp recording of neurons is a labor-intensive and time-consuming procedure. Here, we demonstrate a tool that fully automatically performs electrophysiological recordings in label-free tissue slices. The automation covers the detection of cells in label-free images, calibration of the micropipette movement, approach to the cell with the pipette, formation of the whole-cell configuration, and recording. The cell detection is based on deep learning. The model is trained on a new image database of neurons in unlabeled brain tissue slices. The pipette tip detection and approaching phase use image analysis techniques for precise movements. High-quality measurements are performed on hundreds of human and rodent neurons. We also demonstrate that further molecular and anatomical analysis can be performed on the recorded cells. The software has a diary module that automatically logs patch clamp events. Our tool can multiply the number of daily measurements to help brain research.
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- 2021
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13. Single Cell Mass Cytometry of Non-Small Cell Lung Cancer Cells Reveals Complexity of In vivo And Three-Dimensional Models over the Petri-dish.
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Alföldi R, Balog JÁ, Faragó N, Halmai M, Kotogány E, Neuperger P, Nagy LI, Fehér LZ, Szebeni GJ, and Puskás LG
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- A549 Cells, Carcinoma, Non-Small-Cell Lung genetics, Humans, Lung Neoplasms genetics, Tumor Cells, Cultured, Carcinoma, Non-Small-Cell Lung pathology, Cell Culture Techniques, Flow Cytometry, Lung Neoplasms pathology, Models, Biological, Single-Cell Analysis
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Single cell genomics and proteomics with the combination of innovative three-dimensional (3D) cell culture techniques can open new avenues toward the understanding of intra-tumor heterogeneity. Here, we characterize lung cancer markers using single cell mass cytometry to compare different in vitro cell culturing methods: two-dimensional (2D), carrier-free, or bead-based 3D culturing with in vivo xenografts. Proliferation, viability, and cell cycle phase distribution has been investigated. Gene expression analysis enabled the selection of markers that were overexpressed: TMEM45A, SLC16A3, CD66, SLC2A1, CA9, CD24 , or repressed: EGFR either in vivo or in long-term 3D cultures. Additionally, TRA-1-60, pan-keratins, CD326, Galectin-3, and CD274, markers with known clinical significance have been investigated at single cell resolution. The described twelve markers convincingly highlighted a unique pattern reflecting intra-tumor heterogeneity of 3D samples and in vivo A549 lung cancer cells. In 3D systems CA9, CD24, and EGFR showed higher expression than in vivo. Multidimensional single cell proteome profiling revealed that 3D cultures represent a transition from 2D to in vivo conditions by intermediate marker expression of TRA-1-60, TMEM45A, pan-keratin, CD326, MCT4, Gal-3, CD66, GLUT1, and CD274. Therefore, 3D cultures of NSCLC cells bearing more putative cancer targets should be used in drug screening as the preferred technique rather than the Petri-dish., Competing Interests: The authors declare no conflict of interest.
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- 2019
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14. Expression of GLP-1 receptors in insulin-containing interneurons of rat cerebral cortex.
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Csajbók ÉA, Kocsis ÁK, Faragó N, Furdan S, Kovács B, Lovas S, Molnár G, Likó I, Zvara Á, Puskás LG, Patócs A, and Tamás G
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- Animals, Cytoplasm metabolism, Glucagon-Like Peptide 1 metabolism, Hyperglycemia metabolism, Hypoglycemia metabolism, Male, Neocortex metabolism, Rats, Rats, Wistar, Signal Transduction, Cerebral Cortex metabolism, Glucagon-Like Peptide-1 Receptor metabolism, Insulin metabolism, Interneurons metabolism
- Abstract
Aims/hypothesis: Glucagon-like peptide 1 (GLP-1) receptors are expressed by pancreatic beta cells and GLP-1 receptor signalling promotes insulin secretion. GLP-1 receptor agonists have neural effects and are therapeutically promising for mild cognitive impairment and Alzheimer's disease. Our previous results showed that insulin is released by neurogliaform neurons in the cerebral cortex, but the expression of GLP-1 receptors on insulin-producing neocortical neurons has not been tested. In this study, we aimed to determine whether GLP-1 receptors are present in insulin-containing neurons., Methods: We harvested the cytoplasm of electrophysiologically and anatomically identified neurogliaform interneurons during patch-clamp recordings performed in slices of rat neocortex. Using single-cell digital PCR, we determined copy numbers of Glp1r mRNA and other key genes in neurogliaform cells harvested in conditions corresponding to hypoglycaemia (0.5 mmol/l glucose) and hyperglycaemia (10 mmol/l glucose). In addition, we performed whole-cell patch-clamp recordings on neurogliaform cells to test the effects of GLP-1 receptor agonists for functional validation of single-cell digital PCR results., Results: Single-cell digital PCR revealed GLP-1 receptor expression in neurogliaform cells and showed that copy numbers of mRNA of the Glp1r gene in hyperglycaemia exceeded those in hypoglycaemia by 9.6 times (p < 0.008). Moreover, single-cell digital PCR confirmed co-expression of Glp1r and Ins2 mRNA in neurogliaform cells. Functional expression of GLP-1 receptors was confirmed with whole-cell patch-clamp electrophysiology, showing a reversible effect of GLP-1 on neurogliaform cells. This effect was prevented by pre-treatment with the GLP-1 receptor-specific antagonist exendin-3(9-39) and was absent in hypoglycaemia. In addition, single-cell digital PCR of neurogliaform cells revealed that the expression of transcription factors (Pdx1, Isl1, Mafb) are important in beta cell development., Conclusions/interpretation: Our results provide evidence for the functional expression of GLP-1 receptors in neurons known to release insulin in the cerebral cortex. Hyperglycaemia increases the expression of GLP-1 receptors in neurogliaform cells, suggesting that endogenous incretins and therapeutic GLP-1 receptor agonists might have effects on these neurons, similar to those in pancreatic beta cells.
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- 2019
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15. Sensory Neuropathy Affects Cardiac miRNA Expression Network Targeting IGF-1 , SLC2a-12 , EIF-4e , and ULK-2 mRNAs.
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Bencsik P, Kiss K, Ágg B, Baán JA, Ágoston G, Varga A, Gömöri K, Mendler L, Faragó N, Zvara Á, Sántha P, Puskás LG, Jancsó G, and Ferdinandy P
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- Animals, Capsaicin toxicity, Disease Models, Animal, Eukaryotic Initiation Factor-4E genetics, Gene Expression Profiling, Gene Regulatory Networks, Glucose Transport Proteins, Facilitative genetics, Heart Failure, Diastolic genetics, Insulin-Like Growth Factor I genetics, Male, Polyneuropathies chemically induced, Protein Serine-Threonine Kinases genetics, Rats, Rats, Wistar, Heart Failure, Diastolic etiology, MicroRNAs genetics, Polyneuropathies complications
- Abstract
Background: Here we examined myocardial microRNA (miRNA) expression profile in a sensory neuropathy model with cardiac diastolic dysfunction and aimed to identify key mRNA molecular targets of the differentially expressed miRNAs that may contribute to cardiac dysfunction., Methods: Male Wistar rats were treated with vehicle or capsaicin for 3 days to induce systemic sensory neuropathy. Seven days later, diastolic dysfunction was detected by echocardiography, and miRNAs were isolated from the whole ventricles., Results: Out of 711 known miRNAs measured by miRNA microarray, the expression of 257 miRNAs was detected in the heart. As compared to vehicle-treated hearts, miR-344b , miR-466b , miR-98 , let-7a , miR-1 , miR-206 , and miR-34b were downregulated, while miR-181a was upregulated as validated also by quantitative real time polymerase chain reaction (qRT-PCR). By an in silico network analysis, we identified common mRNA targets (insulin-like growth factor 1 ( IGF-1 ), solute carrier family 2 facilitated glucose transporter member 12 ( SLC2a-12 ), eukaryotic translation initiation factor 4e (EIF-4e ), and Unc-51 like autophagy activating kinase 2 ( ULK-2 )) targeted by at least three altered miRNAs. Predicted upregulation of these mRNA targets were validated by qRT-PCR., Conclusion: This is the first demonstration that sensory neuropathy affects cardiac miRNA expression network targeting IGF-1 , SLC2a-12 , EIF-4e , and ULK-2 , which may contribute to cardiac diastolic dysfunction. These results further support the need for unbiased omics approach followed by in silico prediction and validation of molecular targets to reveal novel pathomechanisms.
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- 2019
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16. Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type.
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Boldog E, Bakken TE, Hodge RD, Novotny M, Aevermann BD, Baka J, Bordé S, Close JL, Diez-Fuertes F, Ding SL, Faragó N, Kocsis ÁK, Kovács B, Maltzer Z, McCorrison JM, Miller JA, Molnár G, Oláh G, Ozsvár A, Rózsa M, Shehata SI, Smith KA, Sunkin SM, Tran DN, Venepally P, Wall A, Puskás LG, Barzó P, Steemers FJ, Schork NJ, Scheuermann RH, Lasken RS, Lein ES, and Tamás G
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- Adult, Aged, Axons ultrastructure, Dendritic Spines metabolism, Dendritic Spines ultrastructure, Gap Junctions metabolism, Gap Junctions ultrastructure, Gene Library, Humans, Male, Polymerase Chain Reaction, Presynaptic Terminals metabolism, Presynaptic Terminals ultrastructure, Pyramidal Cells metabolism, Pyramidal Cells ultrastructure, RNA analysis, RNA genetics, Sequence Analysis, RNA, Cerebral Cortex metabolism, Cerebral Cortex ultrastructure, GABAergic Neurons metabolism, GABAergic Neurons ultrastructure, Transcriptome
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We describe convergent evidence from transcriptomics, morphology, and physiology for a specialized GABAergic neuron subtype in human cortex. Using unbiased single-nucleus RNA sequencing, we identify ten GABAergic interneuron subtypes with combinatorial gene signatures in human cortical layer 1 and characterize a group of human interneurons with anatomical features never described in rodents, having large 'rosehip'-like axonal boutons and compact arborization. These rosehip cells show an immunohistochemical profile (GAD1
+ CCK+ , CNR1- SST- CALB2- PVALB- ) matching a single transcriptomically defined cell type whose specific molecular marker signature is not seen in mouse cortex. Rosehip cells in layer 1 make homotypic gap junctions, predominantly target apical dendritic shafts of layer 3 pyramidal neurons, and inhibit backpropagating pyramidal action potentials in microdomains of the dendritic tuft. These cells are therefore positioned for potent local control of distal dendritic computation in cortical pyramidal neurons.- Published
- 2018
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17. Author Correction: MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium.
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Ágg B, Baranyai T, Makkos A, Vető B, Faragó N, Zvara Á, Giricz Z, Veres DV, Csermely P, Arányi T, Puskás LG, Varga ZV, and Ferdinandy P
- Abstract
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
- Published
- 2018
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18. MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium.
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Ágg B, Baranyai T, Makkos A, Vető B, Faragó N, Zvara Á, Giricz Z, Veres DV, Csermely P, Arányi T, Puskás LG, Varga ZV, and Ferdinandy P
- Subjects
- Animals, Calcineurin metabolism, Down-Regulation, Guanylate Kinases genetics, Guanylate Kinases metabolism, HeLa Cells, Humans, Hypercholesterolemia metabolism, MicroRNAs metabolism, RNA Processing, Post-Transcriptional, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Rats, Wistar, Receptors, Adrenergic, beta-2 metabolism, Calcineurin genetics, Hypercholesterolemia genetics, MicroRNAs genetics, Myocardium metabolism, Receptors, Adrenergic, beta-2 genetics
- Abstract
Little is known about the molecular mechanism including microRNAs (miRNA) in hypercholesterolemia-induced cardiac dysfunction. We aimed to explore novel hypercholesterolemia-induced pathway alterations in the heart by an unbiased approach based on miRNA omics, target prediction and validation. With miRNA microarray we identified forty-seven upregulated and ten downregulated miRNAs in hypercholesterolemic rat hearts compared to the normocholesterolemic group. Eleven mRNAs with at least 4 interacting upregulated miRNAs were selected by a network theoretical approach, out of which 3 mRNAs (beta-2 adrenergic receptor [Adrb2], calcineurin B type 1 [Ppp3r1] and calcium/calmodulin-dependent serine protein kinase [Cask]) were validated with qRT-PCR and Western blot. In hypercholesterolemic hearts, the expression of Adrb2 mRNA was significantly decreased. ADRB2 and PPP3R1 protein were significantly downregulated in hypercholesterolemic hearts. The direct interaction of Adrb2 with upregulated miRNAs was demonstrated by luciferase reporter assay. Gene ontology analysis revealed that the majority of the predicted mRNA changes may contribute to the hypercholesterolemia-induced cardiac dysfunction. In summary, the present unbiased target prediction approach based on global cardiac miRNA expression profiling revealed for the first time in the literature that both the mRNA and protein product of Adrb2 and PPP3R1 protein are decreased in the hypercholesterolemic heart.
- Published
- 2018
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19. Mannich Curcuminoids as Potent Anticancer Agents.
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Gyuris M, Hackler L Jr, Nagy LI, Alföldi R, Rédei E, Marton A, Vellai T, Faragó N, Ózsvári B, Hetényi A, Tóth GK, Sipos P, Kanizsai I, and Puskás LG
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- Animals, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Curcumin analogs & derivatives, Curcumin chemistry, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Male, Mannich Bases chemistry, Mice, Mice, SCID, Molecular Structure, Neoplasms, Experimental drug therapy, Neoplasms, Experimental pathology, Structure-Activity Relationship, Antineoplastic Agents pharmacology, Curcumin pharmacology, Mannich Bases pharmacology
- Abstract
A series of novel curcuminoids were synthesised for the first time via a Mannich-3CR/organocatalysed Claisen-Schmidt condensation sequence. Structure-activity relationship (SAR) studies were performed by applying viability assays and holographic microscopic imaging to these curcumin analogues for anti-proliferative activity against A549 and H1975 lung adenocarcinoma cells. The TNFα-induced NF-κB inhibition and autophagy induction effects correlated strongly with the cytotoxic potential of the analogues. Significant inhibition of tumour growth was observed when the most potent analogue 44 was added in liposomes at one-sixth of the maximally tolerated dose in the A549 xenograft model. The novel spectrum of activity of these Mannich curcuminoids warrants further preclinical investigations., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
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20. Human neuronal changes in brain edema and increased intracranial pressure.
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Faragó N, Kocsis ÁK, Braskó C, Lovas S, Rózsa M, Baka J, Kovács B, Mikite K, Szemenyei V, Molnár G, Ozsvár A, Oláh G, Piszár I, Zvara Á, Patócs A, Barzó P, Puskás LG, and Tamás G
- Subjects
- Adult, Brain Edema pathology, Brain Edema surgery, Female, Gene Expression Regulation, Gray Matter metabolism, Gray Matter pathology, Gray Matter surgery, Humans, Intermediate-Conductance Calcium-Activated Potassium Channels metabolism, Intracranial Hypertension pathology, Intracranial Hypertension surgery, Intracranial Pressure physiology, Male, Membrane Potentials physiology, Middle Aged, Neocortex pathology, Neocortex surgery, Neurons pathology, RNA, Messenger metabolism, Tissue Culture Techniques, Brain Edema metabolism, Intracranial Hypertension metabolism, Neocortex metabolism, Neurons metabolism
- Abstract
Functional and molecular changes associated with pathophysiological conditions are relatively easily detected based on tissue samples collected from patients. Population specific cellular responses to disease might remain undiscovered in samples taken from organs formed by a multitude of cell types. This is particularly apparent in the human cerebral cortex composed of a yet undefined number of neuron types with a potentially different involvement in disease processes. We combined cellular electrophysiology, anatomy and single cell digital PCR in human neurons identified in situ for the first time to assess mRNA expression and corresponding functional changes in response to edema and increased intracranial pressure. In single pyramidal cells, mRNA copy numbers of AQP1, AQP3, HMOX1, KCNN4, SCN3B and SOD2 increased, while CACNA1B, CRH decreased in edema. In addition, single pyramidal cells increased the copy number of AQP1, HTR5A and KCNS1 mRNAs in response to increased intracranial pressure. In contrast to pyramidal cells, AQP1, HMOX1and KCNN4 remained unchanged in single cell digital PCR performed on fast spiking cells in edema. Corroborating single cell digital PCR results, pharmacological and immunohistochemical results also suggested the presence of KCNN4 encoding the α-subunit of KCa3.1 channels in edema on pyramidal cells, but not on interneurons. We measured the frequency of spontaneous EPSPs on pyramidal cells in both pathophysiological conditions and on fast spiking interneurons in edema and found a significant decrease in each case, which was accompanied by an increase in input resistances on both cell types and by a drop in dendritic spine density on pyramidal cells consistent with a loss of excitatory synapses. Our results identify anatomical and/or physiological changes in human pyramidal and fast spiking cells in edema and increased intracranial pressure revealing cell type specific quantitative changes in gene expression. Some of the edema/increased intracranial pressure modulated and single human pyramidal cell verified gene products identified here might be considered as novel pharmacological targets in cell type specific neuroprotection.
- Published
- 2016
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21. The Curcumin Analog C-150, Influencing NF-κB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo.
- Author
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Hackler L Jr, Ózsvári B, Gyuris M, Sipos P, Fábián G, Molnár E, Marton A, Faragó N, Mihály J, Nagy LI, Szénási T, Diron A, Párducz Á, Kanizsai I, and Puskás LG
- Subjects
- Animals, Antineoplastic Agents chemistry, Brain Neoplasms metabolism, Cell Line, Tumor, Cell Proliferation, Drosophila melanogaster, Drug Screening Assays, Antitumor, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Glioblastoma metabolism, Humans, Inhibitory Concentration 50, Melanoma, Experimental, Mice, Neoplasm Transplantation, Rats, Rats, Nude, Receptors, Notch metabolism, Signal Transduction, Transcription, Genetic, Acrylamides chemistry, Brain Neoplasms drug therapy, Curcumin analogs & derivatives, Curcumin chemistry, Glioblastoma drug therapy, NF-kappa B antagonists & inhibitors, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Receptors, Notch antagonists & inhibitors, Unfolded Protein Response drug effects
- Abstract
C-150 a Mannich-type curcumin derivative, exhibited pronounced cytotoxic effects against eight glioma cell lines at micromolar concentrations. Inhibition of cell proliferation by C-150 was mediated by affecting multiple targets as confirmed at transcription and protein level. C-150 effectively reduced the transcription activation of NFkB, inhibited PKC-alpha which are constitutively over-expressed in glioblastoma. The effects of C-150 on the Akt/ Notch signaling were also demonstrated in a Drosophila tumorigenesis model. C-150 reduced the number of tumors in Drosophila with similar efficacy to mitoxantrone. In an in vivo orthotopic glioma model, C-150 significantly increased the median survival of treated nude rats compared to control animals. The multi-target action of C-150, and its preliminary in vivo efficacy would render this curcumin analogue as a potent clinical candidate against glioblastoma.
- Published
- 2016
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22. MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning: protectomiRs.
- Author
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Varga ZV, Zvara A, Faragó N, Kocsis GF, Pipicz M, Gáspár R, Bencsik P, Görbe A, Csonka C, Puskás LG, Thum T, Csont T, and Ferdinandy P
- Subjects
- Animals, Cell Death, Cells, Cultured, Disease Models, Animal, Gene Expression Profiling methods, Gene Expression Regulation, Male, Myocardial Infarction genetics, Myocardial Infarction metabolism, Myocardial Infarction pathology, Myocardial Reperfusion Injury genetics, Myocardial Reperfusion Injury metabolism, Myocardial Reperfusion Injury pathology, Myocytes, Cardiac pathology, Oligonucleotide Array Sequence Analysis, Rats, Rats, Wistar, Real-Time Polymerase Chain Reaction, Reproducibility of Results, Time Factors, Transfection, Ischemic Postconditioning, Ischemic Preconditioning, Myocardial, MicroRNAs metabolism, Myocardial Infarction prevention & control, Myocardial Reperfusion Injury prevention & control, Myocytes, Cardiac metabolism
- Abstract
We aimed to characterize early changes in microRNA expression in acute cardioprotection by ischemic pre- and postconditioning in rat hearts. Hearts isolated from male Wistar rats were subjected to 1) time-matched nonischemic perfusion, 2) ischemia-reperfusion (30 min of coronary occlusion and 120 min of reperfusion), 3) preconditioning (3 × 5 min of coronary occlusion) followed by ischemia-reperfusion, or 4) ischemia-reperfusion with postconditioning (6 × 10 s of global ischemia-reperfusion at the onset of reperfusion). Infarct size was significantly reduced by both interventions. Of 350 different microRNAs assessed by microarray analysis, 147-160 microRNAs showed detectable expression levels. Compared with microRNA alterations induced by ischemia-reperfusion versus time-matched nonischemic controls, five microRNAs were significantly affected by both pre- and postconditioning (microRNA-125b*, microRNA-139-3p, microRNA-320, microRNA-532-3p, and microRNA-188), four microRNAs were significantly affected by preconditioning (microRNA-487b, microRNA-139-5p, microRNA-192, and microRNA-212), and nine microRNAs were significantly affected by postconditioning (microRNA-1, microRNA let-7i, microRNA let-7e, microRNA let-7b, microRNA-181a, microRNA-208, microRNA-328, microRNA-335, and microRNA-503). Expression of randomly selected microRNAs was validated by quantitative real-time PCR. By a systematic comparison of the direction of microRNA expression changes in all groups, we identified microRNAs, specific mimics, or antagomiRs that may have pre- and postconditioning-like cardioprotective effects (protectomiRs). Transfection of selected protectomiRs (mimics of microRNA-139-5p, microRNA-125b*, microRNA let-7b, and inhibitor of microRNA-487b) into cardiac myocytes subjected to simulated ischemia-reperfusion showed a significant cytoprotective effect. This is the first demonstration that the ischemia-reperfusion-induced microRNA expression profile is significantly influenced by both pre- and postconditioning, which shows the involvement of microRNAs in cardioprotective signaling. Moreover, by analysis of microRNA expression patterns in cardioprotection by pre- and postconditioning, specific protectomiRs can be revealed as potential therapeutic tools for the treatment of ischemia-reperfusion injury., (Copyright © 2014 the American Physiological Society.)
- Published
- 2014
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23. GABAergic neurogliaform cells represent local sources of insulin in the cerebral cortex.
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Molnár G, Faragó N, Kocsis ÁK, Rózsa M, Lovas S, Boldog E, Báldi R, Csajbók É, Gardi J, Puskás LG, and Tamás G
- Subjects
- Animals, Excitatory Postsynaptic Potentials physiology, Insulin Secretion, Male, Patch-Clamp Techniques, Polymerase Chain Reaction, Radioimmunoassay, Rats, Rats, Wistar, gamma-Aminobutyric Acid metabolism, Insulin metabolism, Neocortex cytology, Neocortex metabolism, Neuroglia metabolism, Neurons metabolism
- Abstract
Concentrations of insulin in the brain are severalfold higher than blood plasma levels. Insulin in the brain regulates the metabolism, molecular composition, and cognitive performance of microcircuits and reduces food intake; cerebral insulin levels are altered in diabetes, aging, obesity, and Alzheimer's disease. Released by pancreatic β cells, insulin passes the blood-brain barrier, but sources of locally released insulin still remain unclear. We find that insulin is strongly expressed in GABAergic neurogliaform cells in the cerebral cortex of the rat detected by single-cell digital PCR. Focal application of glucose or glibenclamide to neurogliaform cells mimics the excitation suppressing effect of external insulin on local microcircuits via insulin receptors. Thus, neurogliaform cells might link GABAergic and insulinergic action in cortical microcircuits.
- Published
- 2014
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24. MicroRNA-25-dependent up-regulation of NADPH oxidase 4 (NOX4) mediates hypercholesterolemia-induced oxidative/nitrative stress and subsequent dysfunction in the heart.
- Author
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Varga ZV, Kupai K, Szűcs G, Gáspár R, Pálóczi J, Faragó N, Zvara A, Puskás LG, Rázga Z, Tiszlavicz L, Bencsik P, Görbe A, Csonka C, Ferdinandy P, and Csont T
- Subjects
- Animals, Heart, Heart Diseases metabolism, Immunohistochemistry, Male, MicroRNAs genetics, Microscopy, Electron, Transmission, NADPH Oxidase 4, NADPH Oxidases genetics, Oxidative Stress genetics, Rats, Rats, Wistar, Heart Diseases etiology, Heart Diseases genetics, Hypercholesterolemia complications, Hypercholesterolemia genetics, MicroRNAs metabolism, NADPH Oxidases metabolism, Oxidative Stress physiology
- Abstract
Diet-induced hypercholesterolemia leads to oxidative/nitrative stress and subsequent myocardial dysfunction. However, the regulatory role of microRNAs in this phenomenon is unknown. We aimed to investigate, whether hypercholesterolemia-induced myocardial microRNA alterations play a role in the development of oxidative/nitrative stress and in subsequent cardiac dysfunction. Male Wistar rats were fed with 2% cholesterol/0.25% cholate-enriched or standard diet for 12weeks. Serum and tissue cholesterol levels were significantly elevated by cholesterol-enriched diet. Left ventricular end-diastolic pressure was significantly increased in cholesterol-fed rats both in vivo and in isolated perfused hearts, indicating diastolic dysfunction. Myocardial expression of microRNAs was affected by cholesterol-enriched diet as assessed by microarray analysis. MicroRNA-25 showed a significant down-regulation as detected by microarray analysis and QRT-PCR. In silico target prediction revealed NADPH oxidase 4 (NOX4) as a putative target of microRNA-25. NOX4 protein showed significant up-regulation in the hearts of cholesterol-fed rats, while NOX1 and NOX2 remained unaffected. Cholesterol-feeding significantly increased myocardial oxidative/nitrative stress as assessed by dihydroethidium staining, protein oxidation assay, and nitro-tyrosine ELISA, respectively. Direct binding of microRNA-25 mimic to the 3' UTR region of NOX4 was demonstrated using a luciferase reporter assay. Transfection of a microRNA-25 mimic into primary cardiomyocytes decreased superoxide production, while a microRNA-25 inhibitor resulted in an up-regulation of NOX4 protein and an increase in oxidative stress that was attenuated by the NADPH oxidase inhibitor diphenyleneiodonium. Here we demonstrated for the first time that hypercholesterolemia affects myocardial microRNA expression, and by down-regulating microRNA-25 increases NOX4 expression and consequently oxidative/nitrative stress in the heart. We conclude that hypercholesterolemia-induced microRNA alterations play an important role in the regulation of oxidative/nitrative stress and in consequent myocardial dysfunction., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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25. Digital PCR to determine the number of transcripts from single neurons after patch-clamp recording.
- Author
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Faragó N, Kocsis ÁK, Lovas S, Molnár G, Boldog E, Rózsa M, Szemenyei V, Vámos E, Nagy LI, Tamás G, and Puskás LG
- Subjects
- Animals, Cells, Cultured, Gene Expression Profiling methods, Male, MicroRNAs analysis, MicroRNAs genetics, MicroRNAs metabolism, Neurons chemistry, Neurons cytology, Neurons metabolism, RNA, Messenger analysis, RNA, Messenger genetics, Rats, Rats, Wistar, Somatosensory Cortex cytology, Neurons physiology, Patch-Clamp Techniques methods, Polymerase Chain Reaction methods, RNA, Messenger metabolism, Single-Cell Analysis methods
- Abstract
Whole-cell patch-clamp recording enables detection of electrophysiological signals from single neurons as well as harvesting of perisomatic RNA through the patch pipette for subsequent gene expression analysis. Amplification and profiling of RNA with traditional quantitative real-time PCR (qRT-PCR) do not provide exact quantitation due to experimental variation caused by the limited amount of nucleic acid in a single cell. Here we describe a protocol for quantifying mRNA or miRNA expression in individual neurons after patch-clamp recording using high-density nanocapillary digital PCR (dPCR). Expression of a known cell-type dependent marker gene (gabrd), as well as oxidative-stress related induction of hspb1 and hmox1 expression, was quantified in individual neurogliaform and pyramidal cells, respectively. The miRNA mir-132, which plays a role in neurodevelopment, was found to be equally expressed in three different types of neurons. The accuracy and sensitivity of this method were further validated using synthetic spike-in templates and by detecting genes with very low levels of expression.
- Published
- 2013
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26. Q50, an iron-chelating and zinc-complexing agent, improves cardiac function in rat models of ischemia/reperfusion-induced myocardial injury.
- Author
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Korkmaz S, Barnucz E, Loganathan S, Li S, Radovits T, Hegedus P, Zubarevich A, Hirschberg K, Weymann A, Puskás LG, Ózsvári B, Faragó N, Kanizsai I, Fábián G, Gyuris M, Merkely B, Karck M, Szabó C, and Szabó G
- Subjects
- Animals, Disease Models, Animal, Male, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Time Factors, Troponin T blood, Iron Chelating Agents pharmacology, Myocardial Reperfusion Injury blood, Myocardial Reperfusion Injury drug therapy, Myocardial Reperfusion Injury physiopathology, Myocardium metabolism, Zinc
- Abstract
Background: Reperfusion of ischemic myocardium may contribute to substantial cardiac tissue damage, but the addition of iron chelators, zinc or zinc complexes has been shown to prevent heart from reperfusion injury. We investigated the possible beneficial effects of an iron-chelating and zinc-complexing agent, Q50, in rat models of ischemia/reperfusion (I/R)-induced myocardial infarction and on global reversible myocardial I/R injury after heart transplantation., Methods and Results: Rats underwent 45-min myocardial ischemia by left anterior descending coronary artery ligation followed by 24h reperfusion. Vehicle or Q50 (10 mg/kg, IV) were given 5 min before reperfusion. In a heart transplantation model, donor rats received vehicle or Q50 (30 mg/kg, IV) 1h before the onset of ischemia. In myocardial infarcted rats, increased left ventricular end-systolic and end-diastolic volumes were significantly decreased by Q50 post treatment as compared with the sham group. Moreover, in I/R rat hearts, the decreased dP/dtmax and load-independent contractility parameters were significantly increased after Q50. However, Q50 treatment did not reduce infarct size or have any effect on increased plasma cardiac troponin-T-levels. In the rat model of heart transplantation, 1h after reperfusion, decreased left ventricular systolic pressure, dP/dt(max), dP/dt(min) and myocardial ATP content were significantly increased and myocardial protein expression of superoxide dismutase-1 was upregulated after Q50 treatment., Conclusions: In 2 experimental models of I/R, administration of Q50 improved myocardial function. Its mechanisms of action implicate in part the restoration of myocardial high-energy phosphates and upregulation of antioxidant enzymes.
- Published
- 2013
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- View/download PDF
27. Purification of high-quality micro RNA from the heart tissue.
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Faragó N, Zvara A, Varga Z, Ferdinandy P, and Puskás LG
- Subjects
- Animals, Mice, Oligonucleotide Array Sequence Analysis, Rats, Real-Time Polymerase Chain Reaction, MicroRNAs chemistry, Myocardium chemistry
- Abstract
Micro RNAs (miRNA) are an abundant class of small RNAs that regulate the stability and translation of cognate mRNAs. MiRNAs are potential diagnostic markers, moreover, they play an essential role in the development of various heart disesases. In case of limited tissue material, such as, e.g. human biopsies, purification of miRNAs with sufficient yield is critical. Reproducible expression analysis of miRNAs is highly dependent on the quality of the RNA, which is often difficult to achieve from fibrous tissue such as the heart. Several companies developed general purification kits for miRNAs, however, none of them are specialized to fibrotic tissues. Here we describe an optimized miRNA purification protocol that results in high miRNA yield as compared to other methods including trizol-based and column-based protocols. By using our improved protocol, miRNA obtained from heart tissue gave more reproducible results in QRT-PCR analysis and obtained more significant calls (172 vs. 118) during DNA microarray analysis when compared to the commercially available kit. In addition to the heart tissue, the present protocol can be applied to other fibrotic tissues, such as lung or skeletal muscle to isolate high-purity miRNA.
- Published
- 2011
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28. MicroRNA profile of polyunsaturated fatty acid treated glioma cells reveal apoptosis-specific expression changes.
- Author
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Faragó N, Fehér LZ, Kitajka K, Das UN, and Puskás LG
- Subjects
- Antineoplastic Agents, Alkylating pharmacology, Apoptosis Regulatory Proteins genetics, Apoptosis Regulatory Proteins metabolism, Cell Line, Tumor, Dacarbazine analogs & derivatives, Dacarbazine pharmacology, Down-Regulation drug effects, Glioblastoma drug therapy, Glioblastoma metabolism, Glioma drug therapy, Humans, MicroRNAs genetics, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Osmolar Concentration, RNA, Messenger metabolism, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Temozolomide, Apoptosis, Arachidonic Acid metabolism, Docosahexaenoic Acids metabolism, Glioma metabolism, MicroRNAs metabolism, Up-Regulation drug effects, gamma-Linolenic Acid metabolism
- Abstract
Background: Polyunsaturated fatty acids (PUFAs) such as γ-linolenic acid (GLA), arachidonic acid (AA) and docosahexaenoic acid (DHA) have cytotoxic action on glioma cells., Results: We evaluated the cytotoxic action of GLA, AA and DHA on glioma cells with specific reference to the expression of miRNAs. Relative expression of miRNAs were assessed by using high throughput nanocapillary real-time PCR. Most of the miRNA target genes that showed altered expression could be classified as apoptotic genes and were up-regulated by PUFA or temozolomide treatment, while similar treatments resulted in repression of the corresponding mRNAs, such as cox2, irs1, irs2, ccnd1, itgb3, bcl2, sirt1, tp53inp1 and k-ras., Conclusions: Our results highlight involvement of miRNAs in the induction of apoptosis in glioma cells by fatty acids and temozolomide.
- Published
- 2011
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29. Gene and protein expression changes in response to normoxic perfusion in mouse hearts.
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Faragó N, Kocsis GF, Fehér LZ, Csont T, Hackler L Jr, Varga-Orvos Z, Csonka C, Kelemen JZ, Ferdinandy P, and Puskás LG
- Subjects
- Animals, Creatine Kinase metabolism, Gene Expression Regulation, In Vitro Techniques, L-Lactate Dehydrogenase metabolism, Male, Mice, Mice, Inbred Strains, Oligonucleotide Array Sequence Analysis, Perfusion, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Transcription, Genetic, Gene Expression Profiling, Myocardium metabolism, Oxygen metabolism, Protein Biosynthesis, RNA, Messenger biosynthesis
- Abstract
Introduction: Although crystalloid-perfused isolated heart models are widely used in cardiovascular research, there are several limitations of these techniques. Changes in cardiac gene expression pattern due to normoxic perfusion itself have not been studied, despite its potential importance to provide useful information on limitations of this model. Therefore, here we investigated the time-dependent effect of normoxic, normothermic perfusion on global gene expression at mRNA and protein levels., Methods: Hearts from male CFLP mice were perfused according to the Langendorff technique. We assessed relative gene expression changes by DNA microarray analysis of 8000 genes after 0, 60 and 120 min perfusion., Results: Twelve genes exhibited significant up-regulation and 27 showed repression in hearts perfused for 60 or 120 min as compared to 0 min controls. Expression changes of 17 selected genes were verified and an additional 19 genes were examined by real-time quantitative PCR. Genes with altered expression included those coding for Creatin kinase, Lactate dehydrogenase, Voltage-dependent anion channel 1, a Disintegrin and Metalloprotease domain 3, Integrin alpha 7, Long-chain acyl-CoA dehydrogenase, Casein kinase II, Ketohexokinase, Chloride ion current inducer protein, Matrix metalloproteinase 2 and 9, Superoxide dismutases and Nitric oxide synthases, etc., Discussion: Our results show that normoxic crystalloid perfusion itself results in time-dependent changes in cardiac gene expression which should be considered when designing ex vivo perfusion protocols in the mouse heart to mimic cardiac pathologies as many of these genes have been suspected to influence several cardiovascular diseases.
- Published
- 2008
- Full Text
- View/download PDF
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