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Article: miR-218-5p and doxorubicin combination enhances anticancer activity in breast cancer cells through Parkin-dependent mitophagy inhibition.

Naso, Francesco Davide / Bruqi, Krenare / Manzini, Valeria / Chiurchiù, Valerio / D'Onofrio, Mara / Arisi, Ivan / Strappazzon, Flavie

Cell death discovery

2024 Volume 10, Issue 1, Page(s) 149

Abstract: Breast Cancer (BC) is one of the most common tumours, and is known for its ability to develop resistance to chemotherapeutic treatments. Autophagy has been linked to chemotherapeutic response in several types of cancer, highlighting its contribution to ... ...

Abstract	Breast Cancer (BC) is one of the most common tumours, and is known for its ability to develop resistance to chemotherapeutic treatments. Autophagy has been linked to chemotherapeutic response in several types of cancer, highlighting its contribution to this process. However, the role of mitophagy, a selective form of autophagy responsible for damaged mitochondria degradation, in the response to therapies in BC is still unclear. In order to address this point, we analysed the role of mitophagy in the treatment of the most common anticancer drug, doxorubicin (DXR), in different models of BC, such as a luminal A subtype-BC cell line MCF7 cells, cultured in 2-Dimension (2D) or in 3-Dimension (3D), and the triple negative BC (TNBC) cell line MDA-MB-231. Through a microarray analysis, we identified a relationship between mitophagy gene expressions related to the canonical PINK1/Parkin-mediated pathway and DXR treatment in BC cells. Afterwards, we demonstrated that the PINK1/Parkin-dependent mitophagy is indeed induced following DXR treatment and that exogenous expression of a small non-coding RNA, the miRNA-218-5p, known to target mRNA of Parkin, was sufficient to inhibit the DXR-mediated mitophagy in MCF7 and in MDA-MB-231 cells, thereby increasing their sensitivity to DXR. Considering the current challenges involved in BC refractory to treatment, our work could provide a promising approach to prevent tumour resistance and recurrence, potentially leading to the development of an innovative approach to combine mitophagy inhibition and chemotherapy.
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ISSN	2058-7716
ISSN	2058-7716
DOI	10.1038/s41420-024-01914-7
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Article: Targeting the Cation-Chloride Co-Transporter NKCC1 to Re-Establish GABAergic Inhibition and an Appropriate Excitatory/Inhibitory Balance in Selective Neuronal Circuits: A Novel Approach for the Treatment of Alzheimer's Disease.

Capsoni, Simona / Arisi, Ivan / Malerba, Francesca / D'Onofrio, Mara / Cattaneo, Antonino / Cherubini, Enrico

Brain sciences

2022 Volume 12, Issue 6

Abstract: GABA, the main inhibitory neurotransmitter in the adult brain, depolarizes and excites immature neurons because of an initially higher intracellular chloride concentration [ ... ...

Abstract	GABA, the main inhibitory neurotransmitter in the adult brain, depolarizes and excites immature neurons because of an initially higher intracellular chloride concentration [Cl
Language	English
Publishing date	2022-06-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci12060783
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Article: Reduced levels of NGF shift astrocytes toward a neurotoxic phenotype.

Tiberi, Alexia / Carucci, Nicola Maria / Testa, Giovanna / Rizzi, Caterina / Pacifico, Paola / Borgonovo, Giulia / Arisi, Ivan / D'Onofrio, Mara / Brandi, Rossella / Gan, Wen-Biao / Capsoni, Simona / Cattaneo, Antonino

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1165125

Abstract: Nerve growth factor (NGF) is critical for neuronal physiology during development and adulthood. Despite the well-recognized effect of NGF on neurons, less is known about whether NGF can actually affect other cell types in the central nervous system (CNS). ...

Abstract	Nerve growth factor (NGF) is critical for neuronal physiology during development and adulthood. Despite the well-recognized effect of NGF on neurons, less is known about whether NGF can actually affect other cell types in the central nervous system (CNS). In this work, we show that astrocytes are susceptible to changes in ambient levels of NGF. First, we observe that interfering with NGF signaling
Language	English
Publishing date	2023-04-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1165125
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Article ; Online: An ontology-based approach for modelling and querying Alzheimer's disease data.

Taglino, Francesco / Cumbo, Fabio / Antognoli, Giulia / Arisi, Ivan / D'Onofrio, Mara / Perazzoni, Federico / Voyat, Roger / Fiscon, Giulia / Conte, Federica / Canevelli, Marco / Bruno, Giuseppe / Mecocci, Patrizia / Bertolazzi, Paola

BMC medical informatics and decision making

2023 Volume 23, Issue 1, Page(s) 153

Abstract: Background: The recent advances in biotechnology and computer science have led to an ever-increasing availability of public biomedical data distributed in large databases worldwide. However, these data collections are far from being "standardized" so to ...

Abstract	Background: The recent advances in biotechnology and computer science have led to an ever-increasing availability of public biomedical data distributed in large databases worldwide. However, these data collections are far from being "standardized" so to be harmonized or even integrated, making it impossible to fully exploit the latest machine learning technologies for the analysis of data themselves. Hence, facing this huge flow of biomedical data is a challenging task for researchers and clinicians due to their complexity and high heterogeneity. This is the case of neurodegenerative diseases and the Alzheimer's Disease (AD) in whose context specialized data collections such as the one by the Alzheimer's Disease Neuroimaging Initiative (ADNI) are maintained. Methods: Ontologies are controlled vocabularies that allow the semantics of data and their relationships in a given domain to be represented. They are often exploited to aid knowledge and data management in healthcare research. Computational Ontologies are the result of the combination of data management systems and traditional ontologies. Our approach is i) to define a computational ontology representing a logic-based formal conceptual model of the ADNI data collection and ii) to provide a means for populating the ontology with the actual data in the Alzheimer Disease Neuroimaging Initiative (ADNI). These two components make it possible to semantically query the ADNI database in order to support data extraction in a more intuitive manner. Results: We developed: i) a detailed computational ontology for clinical multimodal datasets from the ADNI repository in order to simplify the access to these data; ii) a means for populating this ontology with the actual ADNI data. Such computational ontology immediately makes it possible to facilitate complex queries to the ADNI files, obtaining new diagnostic knowledge about Alzheimer's disease. Conclusions: The proposed ontology will improve the access to the ADNI dataset, allowing queries to extract multivariate datasets to perform multidimensional and longitudinal statistical analyses. Moreover, the proposed ontology can be a candidate for supporting the design and implementation of new information systems for the collection and management of AD data and metadata, and for being a reference point for harmonizing or integrating data residing in different sources.
MeSH term(s)	Humans ; Alzheimer Disease/diagnostic imaging ; Semantics ; Data Management
Language	English
Publishing date	2023-08-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2046490-3
ISSN	1472-6947 ; 1472-6947
ISSN (online)	1472-6947
ISSN	1472-6947
DOI	10.1186/s12911-023-02211-6
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Article ; Online: Plasma Biomarker Profile and Clinical Correlations in Adult Patients With Tuberous Sclerosis Complex.

Orlando, Biagio / Morano, Alessandra / Manzini, Valeria / Cerulli Irelli, Emanuele / Borioni, Maria S / Veroni, Caterina / Salamone, Enrico Michele / D'Amelio, Chiara / Moliterni, Elisa / Giustini, Sandra / Ruffolo, Gabriele / Arisi, Ivan / D'Onofrio, Mara / Giallonardo, Anna T / Piscopo, Paola / Di Bonaventura, Carlo

Neurology

2023 Volume 101, Issue 19, Page(s) e1933–e1938

Abstract: Objectives: Different pathophysiologic mechanisms, especially involving astrocytes, could contribute to tuberous sclerosis complex (TSC). We assessed neurodegeneration and astrocytopathy plasma biomarkers in adult patients with TSC to define TSC ... ...

Abstract	Objectives: Different pathophysiologic mechanisms, especially involving astrocytes, could contribute to tuberous sclerosis complex (TSC). We assessed neurodegeneration and astrocytopathy plasma biomarkers in adult patients with TSC to define TSC biomarker profile and investigate clinical-radiologic correlations. Methods: Patients with TSC aged 15 years or older followed at Policlinico "Umberto I" of Rome were consecutively enrolled (July 2021-June 2022). The plasma levels of the following biomarkers were compared between patients and age/sex-matched healthy controls (HCs): tTau, pTau181, Abeta Results: Thirty-one patients (20 females/11 males; median age 30 years, interquartile range 24-47) and 38 HCs were enrolled. Only GFAP was significantly higher in the whole TSC population than in HCs (132.71 [86.14-231.06] vs 44.80 [32.87-66.76] pg/mL, Discussion: Our exploratory study documented a significant increase of GFAP plasma concentration in adult patients with TSC, correlated with their neurologic severity, supporting the central role of astrocytopathy in TSC pathophysiology.
MeSH term(s)	Male ; Female ; Humans ; Adult ; Autism Spectrum Disorder/genetics ; Tuberous Sclerosis/genetics ; Biomarkers ; Astrocytes ; Genotype ; Glial Fibrillary Acidic Protein/genetics
Chemical Substances	Biomarkers ; Glial Fibrillary Acidic Protein
Language	English
Publishing date	2023-08-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000207799
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Article ; Online: Cladribine and ocrelizumab induce differential miRNA profiles in peripheral blood mononucleated cells from relapsing-remitting multiple sclerosis patients.

Arisi, Ivan / Malimpensa, Leonardo / Manzini, Valeria / Brandi, Rossella / Gosetti di Sturmeck, Tommaso / D'Amelio, Chiara / Crisafulli, Sebastiano / Ferrazzano, Gina / Belvisi, Daniele / Malerba, Francesca / Florio, Rita / Pascale, Esterina / Soreq, Hermona / Salvetti, Marco / Cattaneo, Antonino / D'Onofrio, Mara / Conte, Antonella

Frontiers in immunology

2023 Volume 14, Page(s) 1234869

Abstract: Background and objectives: Multiple sclerosis (MS) is a chronic, progressive neurological disease characterized by early-stage neuroinflammation, neurodegeneration, and demyelination that involves a spectrum of heterogeneous clinical manifestations in ... ...

Abstract	Background and objectives: Multiple sclerosis (MS) is a chronic, progressive neurological disease characterized by early-stage neuroinflammation, neurodegeneration, and demyelination that involves a spectrum of heterogeneous clinical manifestations in terms of disease course and response to therapy. Even though several disease-modifying therapies (DMTs) are available to prevent MS-related brain damage-acting on the peripheral immune system with an indirect effect on MS lesions-individualizing therapy according to disease characteristics and prognostic factors is still an unmet need. Given that deregulated miRNAs have been proposed as diagnostic tools in neurodegenerative/neuroinflammatory diseases such as MS, we aimed to explore miRNA profiles as potential classifiers of the relapsing-remitting MS (RRMS) patients' prospects to gain a more effective DMT choice and achieve a preferential drug response. Methods: A total of 25 adult patients with RRMS were enrolled in a cohort study, according to the latest McDonald criteria before (pre-cladribine, pre-CLA; pre-ocrelizumab, pre-OCRE, time T0) and after high-efficacy DMTs, time T1, 6 months post-CLA ( Results: First, the miRNA profiles of pre-CLA or pre-OCRE RRMS patients compared to healthy controls identified modulated miRNA patterns (40 and seven miRNAs, respectively). A direct comparison of the two pre-treatment groups at T0 and T1 revealed more pro-inflammatory patterns in the pre-CLA miRNA profiles. Moreover, both DMTs emerged as being capable of reverting some dysregulated miRNAs toward a protective phenotype. Both drug-dependent miRNA profiles and specific miRNAs, such as miR-199a-3p, miR-29b-3p, and miR-151a-3p, emerged as potentially involved in these drug-induced mechanisms. This enabled the selection of miRNAs correlated to clinical features and the related miRNA-mRNA network. Discussion: These data support the hypothesis of specific deregulated miRNAs as putative biomarkers in RRMS patients' stratification and DMT drug response.
MeSH term(s)	Adult ; Humans ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics ; Cladribine ; Multiple Sclerosis/drug therapy ; Leukocytes, Mononuclear ; Cohort Studies ; MicroRNAs
Chemical Substances	Cladribine (47M74X9YT5) ; ocrelizumab (A10SJL62JY) ; MicroRNAs
Language	English
Publishing date	2023-12-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1234869
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Article: The Encapsulation of Citicoline within Solid Lipid Nanoparticles Enhances Its Capability to Counteract the 6-Hydroxydopamine-Induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells.

Margari, Andrea / Monteduro, Anna Grazia / Rizzato, Silvia / Capobianco, Loredana / Crestini, Alessio / Rivabene, Roberto / Piscopo, Paola / D'Onofrio, Mara / Manzini, Valeria / Trapani, Giuseppe / Quarta, Alessandra / Maruccio, Giuseppe / Ventra, Carmelo / Lieto, Luigi / Trapani, Adriana

Pharmaceutics

2022 Volume 14, Issue 9

Abstract: 1) Backgrond: Considering the positive effects of citicoline (CIT) in the management of some neurodegenerative diseases, the aim of this work was to develop CIT-Loaded Solid Lipid Nanoparticles (CIT-SLNs) for enhancing the therapeutic use of CIT in ... ...

Abstract	(1) Backgrond: Considering the positive effects of citicoline (CIT) in the management of some neurodegenerative diseases, the aim of this work was to develop CIT-Loaded Solid Lipid Nanoparticles (CIT-SLNs) for enhancing the therapeutic use of CIT in parkinsonian syndrome; (2) Methods: CIT-SLNs were prepared by the melt homogenization method using the self-emulsifying lipid Gelucire
Language	English
Publishing date	2022-08-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14091827
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Article ; Online: Biomarkers and phenotypic expression in Alzheimer's disease: exploring the contribution of frailty in the Alzheimer's Disease Neuroimaging Initiative.

Canevelli, Marco / Arisi, Ivan / Bacigalupo, Ilaria / Arighi, Andrea / Galimberti, Daniela / Vanacore, Nicola / D'Onofrio, Mara / Cesari, Matteo / Bruno, Giuseppe

GeroScience

2020 Volume 43, Issue 2, Page(s) 1039–1051

Abstract: The present study aimed at investigating if the main biomarkers of Alzheimer's disease (AD) neuropathology and their association with cognitive disturbances and dementia are modified by the individual's frailty status. We performed a cross-sectional ... ...

Abstract	The present study aimed at investigating if the main biomarkers of Alzheimer's disease (AD) neuropathology and their association with cognitive disturbances and dementia are modified by the individual's frailty status. We performed a cross-sectional analysis of data from participants with normal cognition, mild cognitive impairment (MCI), and AD dementia enrolled in the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) study. Frailty was operationalized by computing a 40-item Frailty Index (FI). The following AD biomarkers were considered and analyzed according to the participants' frailty status: CSF Aβ
MeSH term(s)	Alzheimer Disease/diagnostic imaging ; Amyloid beta-Peptides ; Biomarkers ; Cross-Sectional Studies ; Frailty/diagnostic imaging ; Humans ; Neuroimaging
Chemical Substances	Amyloid beta-Peptides ; Biomarkers
Language	English
Publishing date	2020-11-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-020-00293-y
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Article ; Online: Neurons Generated by Mouse ESCs with Hippocampal or Cortical Identity Display Distinct Projection Patterns When Co-transplanted in the Adult Brain.

Terrigno, Marco / Busti, Irene / Alia, Claudia / Pietrasanta, Marta / Arisi, Ivan / D'Onofrio, Mara / Caleo, Matteo / Cremisi, Federico

Stem cell reports

2018 Volume 10, Issue 3, Page(s) 1016–1029

Abstract: The capability of generating neural precursor cells with distinct types of regional identity in vitro has recently opened new opportunities for cell replacement in animal models of neurodegenerative diseases. By manipulating Wnt and BMP signaling, we ... ...

Abstract	The capability of generating neural precursor cells with distinct types of regional identity in vitro has recently opened new opportunities for cell replacement in animal models of neurodegenerative diseases. By manipulating Wnt and BMP signaling, we steered the differentiation of mouse embryonic stem cells (ESCs) toward isocortical or hippocampal molecular identity. These two types of cells showed different degrees of axonal outgrowth and targeted different regions when co-transplanted in healthy or lesioned isocortex or in hippocampus. In hippocampus, only precursor cells with hippocampal molecular identity were able to extend projections, contacting CA3. Conversely, isocortical-like cells were capable of extending long-range axonal projections only when transplanted in motor cortex, sending fibers toward both intra- and extra-cortical targets. Ischemic damage induced by photothrombosis greatly enhanced the capability of isocortical-like cells to extend far-reaching projections. Our results indicate that neural precursors generated by ESCs carry intrinsic signals specifying axonal extension in different environments.
MeSH term(s)	Animals ; Axons/physiology ; Cell Differentiation/physiology ; Cells, Cultured ; Hippocampus/physiology ; Mice ; Motor Cortex/physiology ; Mouse Embryonic Stem Cells/physiology ; Neocortex/physiology ; Neurogenesis/physiology ; Neurons/physiology ; Transplantation/methods
Language	English
Publishing date	2018-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2018.01.010
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Article ; Online: Genomic and physiological resilience in extreme environments are associated with a secure attachment style.

Caputo, Viviana / Pacilli, Maria Giuseppina / Arisi, Ivan / Mazza, Tommaso / Brandi, Rossella / Traversa, Alice / Casasanta, Giampietro / Pisa, Edoardo / Sonnessa, Michele / Healey, Beth / Moggio, Lorenzo / D'Onofrio, Mara / Alleva, Enrico / Macrì, Simone

Translational psychiatry

2020 Volume 10, Issue 1, Page(s) 185

Abstract: Understanding individual capability to adjust to protracted confinement and isolation may inform adaptive plasticity and disease vulnerability/resilience, and may have long-term implications for operations requiring prolonged presence in distant and ... ...

Abstract	Understanding individual capability to adjust to protracted confinement and isolation may inform adaptive plasticity and disease vulnerability/resilience, and may have long-term implications for operations requiring prolonged presence in distant and restricted environments. Individual coping depends on many different factors encompassing psychological dispositional traits, endocrine reactivity and their underlying molecular mechanisms (e.g. gene expression). A positive view of self and others (secure attachment style) has been proposed to promote individual resilience under extreme environmental conditions. Here, we tested this hypothesis and investigated the underlying molecular mechanisms in 13 healthy volunteers confined and isolated for 12 months in a research station located 1670 km away from the south geographic pole on the Antarctic Plateau at 3233 m above sea level. Study participants, stratified for attachment style, were characterised longitudinally (before, during and after confinement) for their psychological appraisal of the stressful nature of the expedition, diurnal fluctuations in endocrine stress reactivity, and gene expression profiling (transcriptomics). Predictably, a secure attachment style was associated with reduced psychological distress and endocrine vulnerability to stress. In addition, while prolonged confinement and isolation remarkably altered overall patterns of gene expression, such alteration was largely reduced in individuals characterised by a secure attachment style. Furthermore, increased resilience was associated with a reduced expression of genes involved in energy metabolism (mitochondrial function and oxidative phosphorylation). Ultimately, our data indicate that a secure attachment style may favour individual resilience in extreme environments and that such resilience can be mapped onto identifiable molecular substrates.
MeSH term(s)	Adaptation, Psychological ; Extreme Environments ; Genomics ; Humans ; Object Attachment ; Personality ; Resilience, Psychological ; Stress, Psychological
Language	English
Publishing date	2020-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-020-00869-4
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