المؤلفون: Laura Micheli, Giorgio D'Andrea, Teresa Maria Creanza, Daniel Volpe, Nicola Ancona, Raffaella Scardigli, Felice Tirone

المصدر: Frontiers in Cell and Developmental Biology, Vol 11 (2023)

مصطلحات موضوعية: adult neurogenesis, aging, dentate gyrus, neural stem cells, self-renewal, physical exercise, Biology (General), QH301-705.5

الوصف: Throughout adulthood neural stem cells divide in neurogenic niches–the dentate gyrus of the hippocampus and the subventricular zone–producing progenitor cells and new neurons. Stem cells self-renew, thus preserving their pool. Furthermore, the number of stem/progenitor cells in the neurogenic niches decreases with age. We have previously demonstrated that the cyclin-dependent kinase inhibitor p16Ink4a maintains, in aged mice, the pool of dentate gyrus stem cells by preventing their activation after a neurogenic stimulus such as exercise (running). We showed that, although p16Ink4a ablation by itself does not activate stem/progenitor cells, exercise strongly induced stem cell proliferation in p16Ink4a knockout dentate gyrus, but not in wild-type. As p16Ink4a regulates stem cell self-renewal during aging, we sought to profile the dentate gyrus transcriptome from p16Ink4a wild-type and knockout aged mice, either sedentary or running for 12 days. By pairwise comparisons of differentially expressed genes and by correlative analyses through the DESeq2 software, we identified genes regulated by p16Ink4a deletion, either without stimulus (running) added, or following running. The p16Ink4a knockout basic gene signature, i.e., in sedentary mice, involves upregulation of apoptotic, neuroinflammation- and synaptic activity-associated genes, suggesting a reactive cellular state. Conversely, another set of 106 genes we identified, whose differential expression specifically reflects the pattern of proliferative response of p16 knockout stem cells to running, are involved in processes that regulate stem cell activation, such as synaptic function, neurotransmitter metabolism, stem cell proliferation control, and reactive oxygen species level regulation. Moreover, we analyzed the regulation of these stem cell-specific genes after a second running stimulus. Surprisingly, the second running neither activated stem cell proliferation in the p16Ink4a knockout dentate gyrus nor changed the expression of these genes, confirming that they are correlated to the stem cell reactivity to stimulus, a process where they may play a role regulating stem cell activation.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcell.2023.1270892/fullTest; https://doaj.org/toc/2296-634XTest

الوصول الحر: https://doaj.org/article/65fdf10c0772421cb2c4932a219e6b93Test

المؤلفون: Laura Micheli, Teresa Maria Creanza, Manuela Ceccarelli, Giorgio D’Andrea, Giacomo Giacovazzo, Nicola Ancona, Roberto Coccurello, Raffaella Scardigli, Felice Tirone

المصدر: Frontiers in Cell and Developmental Biology, Vol 9 (2021)

مصطلحات موضوعية: adult neurogenesis, aging, dentate gyrus, neural stem cells, self-renewal, alpha-synuclein (Snca), Biology (General), QH301-705.5

الوصف: The dentate gyrus of the hippocampus and the subventricular zone are neurogenic niches where neural stem and progenitor cells replicate throughout life to generate new neurons. The Btg1 gene maintains the stem cells of the neurogenic niches in quiescence. The deletion of Btg1 leads to an early transient increase of stem/progenitor cells division, followed, however, by a decrease during adulthood of their proliferative capability, accompanied by apoptosis. Since a physiological decrease of neurogenesis occurs during aging, the Btg1 knockout mouse may represent a model of neural aging. We have previously observed that the defective neurogenesis of the Btg1 knockout model is rescued by the powerful neurogenic stimulus of physical exercise (running). To identify genes responsible for stem and progenitor cells maintenance, we sought here to find genes underlying this premature neural aging, and whose deregulated expression could be rescued by running. Through RNA sequencing we analyzed the transcriptomic profiles of the dentate gyrus isolated from Btg1 wild-type or Btg1 knockout adult (2-month-old) mice submitted to physical exercise or sedentary. In Btg1 knockout mice, 545 genes were deregulated, relative to wild-type, while 2081 genes were deregulated by running. We identified 42 genes whose expression was not only down-regulated in the dentate gyrus of Btg1 knockout, but was also counter-regulated to control levels by running in Btg1 knockout mice, vs. sedentary. Among these 42 counter-regulated genes, alpha-synuclein (Snca), Fos, Arc and Npas4 showed significantly greater differential regulation. These genes control neural proliferation, apoptosis, plasticity and memory and are involved in aging. In particular, Snca expression decreases during aging. We tested, therefore, whether an Snca-expressing lentivirus, by rescuing the defective Snca levels in the dentate gyrus of Btg1 knockout mice, could also reverse the aging phenotype, in particular the defective neurogenesis. We found that the exogenous expression of Snca reversed the Btg1 knockout-dependent decrease of stem cell proliferation as well as the increase of progenitor cell apoptosis. This indicates that Snca has a functional role in the process of neural aging observed in this model, and also suggests that Snca acts as a positive regulator of stem cell maintenance.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcell.2021.696684/fullTest; https://doaj.org/toc/2296-634XTest

الوصول الحر: https://doaj.org/article/5a9e089856fc4da7b5fb8cc8ccec19daTest

المؤلفون: Laura Quintieri, Marzia Giribaldi, Maria Gabriella Giuffrida, Teresa Maria Creanza, Nicola Ancona, Laura Cavallarin, Maria De Angelis, Leonardo Caputo

المصدر: Frontiers in Microbiology, Vol 9 (2018)

مصطلحات موضوعية: meat starter, curing agents, adaptive responses, 2DE/MALDI-TOF/TOF-MS, KEGG enrichment, phenotypic microarray, Microbiology, QR1-502

الوصف: The viability and competitiveness of Staphylococcus xylosus in meat mostly depend on the ability to adapt itself to rapid oxygen and nutrients depletion during meat fermentation. The utilization of nitrite instead of oxygen becomes a successful strategy for this strain to improve its performance in anaerobiosis; however, metabolic pathways of this strain underlying this adaptation, are partially known. The aim of this study was to provide an overview on proteomic changes of S. xylosus DSM 20266T cultured under anaerobiosis and nitrite exposure. Thus, two different cultures of this strain, supplemented or not with nitrite, were in vitro incubated in aerobiosis and anaerobiosis monitoring cell viability, pH, oxidation reduction potential and nitrite content. Protein extracts, obtained from cells, collected as nitrite content was depleted, were analyzed by 2DE/MALDI-TOF/TOF-MS. Results showed that DSM 20266T growth was significantly sustained by nitrite in anaerobiosis, whereas no differences were found in aerobiosis. Accordingly, nitrite content was depleted after 13 h only in anaerobiosis. At this time of sampling, a comparative proteomic analysis showed 45 differentially expressed proteins. Most differences were found between aerobic and anaerobic cultures without nitrite; the induction of glycolytic enzymes and glyoxylate cycle, the reduction of TCA enzymes, and acetate fermentation were found in anaerobiosis to produce ATP and maintain the cell redox balance. In anaerobic cultures the nitrite supplementation partially restored TCA cycle, and reduced the amount of glycolytic enzymes. These results were confirmed by phenotypic microarray that, for the first time, was carried out on cell previously adapted at the different growth conditions. Overall, metabolic changes were similar between aerobiosis and anaerobiosis NO2-adapted cells, whilst cells grown under anaerobiosis showed different assimilation profiles by confirming proteomic data; indeed, these latter extensively assimilated substrates addressed at both supplying glucose for glycolysis or fueling alternative pathways to TCA cycle. In conclusion, metabolic pathways underlying the ability of S. xylosus to adapt itself to oxygen starvation were revealed; the addition of nitrite allowed S. xylosus to take advantage of nitrite to this condition, restoring some metabolic pathway underlying aerobic behavior of the strain.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fmicb.2018.02275/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/0b7dae5f5fba47929740bb7064d468a0Test

المؤلفون: Antonella Maglietta, Rosalia Maglietta, Teresa Staiano, Ramona Bertoni, Nicola Ancona, Giancarlo Marra, Leonardo Resta

المصدر: PLoS ONE, Vol 11, Iss 7, p e0159373 (2016)

مصطلحات موضوعية: Medicine, Science

الوصف: Little is known about the immunoediting process in precancerous lesions. We explored this aspect of benign colorectal adenomas with a descriptive analysis of the immune pathways and immune cells whose regulation is linked to the morphology and size of these lesions. Two series of polypoid and nonpolypoid colorectal adenomas were used in this study: 1) 84 samples (42 lesions, each with matched samples of normal mucosa) whose gene expression data were used to quantify the tumor morphology- and size-related dysregulation of immune pathways collected in the Molecular Signature Database, using Gene Set Enrichment Analysis; 2) 40 other lesions examined with immunohistochemistry to quantify the presence of immune cells in the stromal compartment. In the analysis of transcriptomic data, 429 immune pathways displayed significant differential regulation in neoplasms of different morphology and size. Most pathways were significantly upregulated or downregulated in polypoid lesions versus nonpolypoid lesions (regardless of size). Differential pathway regulation associated with lesion size was observed only in polypoid neoplasms. These findings were mirrored by tissue immunostaining with CD4, CD8, FOXP3, MHC-I, CD68, and CD163 antibodies: stromal immune cell counts (mainly T lymphocytes and macrophages) were significantly higher in polypoid lesions. Certain markers displayed significant size-related differences regardless of lesion morphology. Multivariate analysis of variance showed that the marker panel clearly discriminated between precancerous lesions of different morphologies and sizes. Statistical analysis of immunostained cell counts fully support the results of the transcriptomic data analysis: the density of infiltration of most immune cells in the stroma of polypoid precancerous lesions was significantly higher than that observed in nonpolypoid lesions. Large neoplasms also have more immune cells in their stroma than small lesions. Immunoediting in precancerous colorectal tumors may vary with lesion morphology and stage of development, and this variability could influence a given lesion's trajectory to cancer.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC4956166?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/883e44ce0cb34109889016edecf36324Test

المؤلفون: Orazio Palmieri, Teresa Maria Creanza, Fabrizio Bossa, Tiziana Latiano, Giuseppe Corritore, Orazio Palumbo, Giuseppina Martino, Giuseppe Biscaglia, Daniela Scimeca, Massimo Carella, Nicola Ancona, Angelo Andriulli, Anna Latiano

المصدر: International Journal of Molecular Sciences, Vol 18, Iss 10, p 2113 (2017)

مصطلحات موضوعية: n/a, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: The authors would like to indicate that Dr. Orazio Palmieri and Dr. Teresa Maria Creanza contributed equally to the work published in the International Journal of Molecular Sciences [1] [...]

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/18/10/2113Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/ced0e28a0df9482aaf677e43aee52b43Test

المؤلفون: Orazio Palmieri, Teresa Maria Creanza, Fabrizio Bossa, Tiziana Latiano, Giuseppe Corritore, Orazio Palumbo, Giuseppina Martino, Giuseppe Biscaglia, Daniela Scimeca, Massimo Carella, Nicola Ancona, Angelo Andriulli, Anna Latiano

المصدر: International Journal of Molecular Sciences, Vol 18, Iss 7, p 1580 (2017)

مصطلحات موضوعية: Crohn’s disease, microRNA, mRNA, differential expression analysis, microRNA–mRNA co-expression, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Crohn’s disease (CD) is a debilitating inflammatory bowel disease (IBD) that emerges due to the influence of genetic and environmental factors. microRNAs (miRNAs) have been identified in the tissue and sera of IBD patients and may play an important role in the induction of IBD. Our study aimed to identify differentially expressed miRNAs and miRNAs with the ability to alter transcriptome activity by comparing inflamed tissue samples with their non-inflamed counterparts. We studied changes in miRNA–mRNA interactions associated with CD by examining their differential co-expression relative to normal mucosa from the same patients. Correlation changes between the two conditions were incorporated into scores of predefined gene sets to identify biological processes with altered miRNA-mediated control. Our study identified 28 miRNAs differentially expressed (p-values < 0.01), of which 14 are up-regulated. Notably, our differential co-expression analysis highlights microRNAs (i.e., miR-4284, miR-3194 and miR-21) that have known functional interactions with key mechanisms implicated in IBD. Most of these miRNAs cannot be detected by differential expression analysis that do not take into account miRNA–mRNA interactions. The identification of differential miRNA–mRNA co-expression patterns will facilitate the investigation of the miRNA-mediated molecular mechanisms underlying CD pathogenesis and could suggest novel drug targets for validation.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/18/7/1580Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/f1ac963e82164b63b4a471c9d42277e4Test

المؤلفون: Roberto Anglani, Teresa M Creanza, Vania C Liuzzi, Ada Piepoli, Anna Panza, Angelo Andriulli, Nicola Ancona

المصدر: PLoS ONE, Vol 9, Iss 1, p e87075 (2014)

مصطلحات موضوعية: Medicine, Science

الوصف: Differential gene expression profiling studies have lead to the identification of several disease biomarkers. However, the oncogenic alterations in coding regions can modify the gene functions without affecting their own expression profiles. Moreover, post-translational modifications can modify the activity of the coded protein without altering the expression levels of the coding gene, but eliciting variations to the expression levels of the regulated genes. These considerations motivate the study of the rewiring of networks co-expressed genes as a consequence of the aforementioned alterations in order to complement the informative content of differential expression. We analyzed 339 mRNAomes of five distinct cancer types to find single genes that presented co-expression patterns strongly differentiated between normal and tumor phenotypes. Our analysis of differentially connected genes indicates the loss of connectivity as a common topological trait of cancer networks, and unveils novel candidate cancer genes. Moreover, our integrated approach that combines the differential expression together with the differential connectivity improves the classic enrichment pathway analysis providing novel insights on putative cancer gene biosystems not still fully investigated.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3904972?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/d61796d9f8ef49dc99ace29aa5440f10Test

المؤلفون: Teresa Maria Creanza, Maria Liguori, Sabino Liuni, Nicoletta Nuzziello, Nicola Ancona

المصدر: International Journal of Molecular Sciences, Vol 17, Iss 6, p 936 (2016)

مصطلحات موضوعية: gene expression, multiple sclerosis, gene networks, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Differential gene expression analyses to investigate multiple sclerosis (MS) molecular pathogenesis cannot detect genes harboring genetic and/or epigenetic modifications that change the gene functions without affecting their expression. Differential co-expression network approaches may capture changes in functional interactions resulting from these alterations. We re-analyzed 595 mRNA arrays from publicly available datasets by studying changes in gene co-expression networks in MS and in response to interferon (IFN)-β treatment. Interestingly, MS networks show a reduced connectivity relative to the healthy condition, and the treatment activates the transcription of genes and increases their connectivity in MS patients. Importantly, the analysis of changes in gene connectivity in MS patients provides new evidence of association for genes already implicated in MS by single-nucleotide polymorphism studies and that do not show differential expression. This is the case of amiloride-sensitive cation channel 1 neuronal (ACCN1) that shows a reduced number of interacting partners in MS networks, and it is known for its role in synaptic transmission and central nervous system (CNS) development. Furthermore, our study confirms a deregulation of the vitamin D system: among the transcription factors that potentially regulate the deregulated genes, we find TCF3 and SP1 that are both involved in vitamin D3-induced p27Kip1 expression. Unveiling differential network properties allows us to gain systems-level insights into disease mechanisms and may suggest putative targets for the treatment.

وصف الملف: electronic resource

العلاقة: http://www.mdpi.com/1422-0067/17/6/936Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/d7ed2059657f4b3fb069f1736c0c7e04Test

المؤلفون: Teresa Maria Creanza, Giuseppe Lamanna, Pietro Delre, Marialessandra Contino, Nicola Corriero, Michele Saviano, Giuseppe Felice Mangiatordi, Nicola Ancona

المصدر: Journal of Chemical Information and Modeling. 62:1411-1424

مصطلحات موضوعية: Deep Learning, Databases, Factual, General Chemical Engineering, Neural Networks, Computer, General Chemistry, Library and Information Sciences, Algorithms, Computer Science Applications

الوصف: In this paper, we present a deep learning algorithm for automated design of druglike analogues (DeLA-Drug), a recurrent neural network (RNN) model composed of two long short-term memory (LSTM) layers and conceived for data-driven generation of similar-to-bioactive compounds. DeLA-Drug captures the syntax of SMILES strings of more than 1 million compounds belonging to the ChEMBL28 database and, by employing a new strategy called sampling with substitutions (SWS), generates molecules starting from a single user-defined query compound. Remarkably, the algorithm preserves druglikeness and synthetic accessibility of the known bioactive compounds present in the ChEMBL28 repository. The absence of any time-demanding fine-tuning procedure enables DeLA-Drug to perform a fast generation of focused libraries for further high-throughput screening and makes it a suitable tool for performing

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::49c8099d263be4497ff884d5be68779eTest
https://doi.org/10.1021/acs.jcim.2c00205Test

المؤلفون: Teresa Maria, Creanza, Pietro, Delre, Nicola, Ancona, Giovanni, Lentini, Michele, Saviano, Giuseppe Felice, Mangiatordi

المصدر: Journal of chemical information and modeling. 61(9)

مصطلحات موضوعية: Molecular Docking Simulation, Benchmarking, Cryoelectron Microscopy, Potassium Channel Blockers, Humans, Ether-A-Go-Go Potassium Channels

الوصف: Drug-induced blockade of the human ether-à-go-go-related gene (

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::4992cc10a0b6e906d21cb89d3fa9b0f6Test
https://pubmed.ncbi.nlm.nih.gov/34506150Test