12 results on '"Spallotta, Francesco"'
Search Results
2. N ε -lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart
- Author
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Colussi, Claudia, Rosati, Jessica, Straino, Stefania, Spallotta, Francesco, Berni, Roberta, Stilli, Donatella, Rossi, Stefano, Musso, Ezio, Macchi, Emilio, Mai, Antonello, Sbardella, Gianluca, Castellano, Sabrina, Chimenti, Cristina, Frustaci, Andrea, Nebbioso, Angela, Altucci, Lucia, Capogrossi, Maurizio C., Gaetano, Carlo, and Olson, Eric N.
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- 2011
3. Gastrointestinal Cancer Patient Nutritional Management: From Specific Needs to Novel Epigenetic Dietary Approaches.
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Cencioni, Chiara, Trestini, Ilaria, Piro, Geny, Bria, Emilio, Tortora, Giampaolo, Carbone, Carmine, and Spallotta, Francesco
- Abstract
Nutritional habits impinge on the health of the gastrointestinal (GI) tract, contributing to GI disorder progression. GI cancer is a widespread and aggressive tumor sensitive to nutritional changes. Indeed, specific nutritional expedients can be adopted to prevent GI cancer onset and to slow down disease activity. Moreover, the patient's nutritional status impacts prognosis, quality of life, and chemotherapy tolerance. These patients encounter the highest frequency of malnourishment risk, a condition that can progressively evolve into cachexia. Clinical studies dealing with this topic stressed the importance of nutritional counseling and put under the spotlight nutrient delivery, the type of nutrient supplementation, and timing for the start of nutritional management. A medical practitioner well-prepared on the topic of nutrition and cancer should operate in the clinical team dedicated to these oncological patients. This specific expertise needs to be implemented as soon as possible to adopt nutritional interventions and establish a proper patient-tailored dietary regimen. The nutritional gap closure should be prompt during anticancer treatment to stabilize weight loss, improve treatment tolerability, and ameliorate survival rate. Recently, novel nutritional approaches were investigated to target the bidirectional link between epigenetics and metabolism, whose alteration supports the onset, progression, and therapeutic response of GI cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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4. Design and synthesis of N-benzoyl amino acid derivatives as DNA methylation inhibitors.
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Garella, Davide, Atlante, Sandra, Borretto, Emily, Cocco, Mattia, Giorgis, Marta, Costale, Annalisa, Stevanato, Livio, Miglio, Gianluca, Cencioni, Chiara, Fernández ‐ de Gortari, Eli, Medina ‐ Franco, José L., Spallotta, Francesco, Gaetano, Carlo, and Bertinaria, Massimo
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BENZOYL compounds ,AMINO acids ,DNA methylation ,GLUTAMIC acid ,MOLECULAR docking ,EPIGENETICS - Abstract
The inhibition of human DNA Methyl Transferases ( DNMT) is a novel promising approach to address the epigenetic dysregulation of gene expression in different diseases. Inspired by the validated virtual screening hit NSC137546, a series of N-benzoyl amino acid analogues was synthesized and obtained compounds were assessed for their ability to inhibit DNMT-dependent DNA methylation in vitro. The biological screening allowed the definition of a set of preliminary structure-activity relationships and the identification of compounds promising for further development. Among the synthesized compounds, L-glutamic acid derivatives 22, 23, and 24 showed the highest ability to prevent DNA methylation in a total cell lysate. Compound 22 inhibited DNMT1 and DNMT3A activity in a concentration-dependent manner in the micromolar range. In addition, compound 22 proved to be stable in human serum and it was thus selected as a starting point for further biological studies. [ABSTRACT FROM AUTHOR]
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- 2016
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5. RNA-seq of the aging brain in the short-lived fish N. furzeri - conserved pathways and novel genes associated with neurogenesis.
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Baumgart, Mario, Groth, Marco, Priebe, Steffen, Savino, Aurora, Testa, Giovanna, Dix, Andreas, Ripa, Roberto, Spallotta, Francesco, Gaetano, Carlo, Ori, Michela, Terzibasi Tozzini, Eva, Guthke, Reinhard, Platzer, Matthias, and Cellerino, Alessandro
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DEVELOPMENTAL neurobiology ,NUCLEOTIDE sequence ,FISH genetics ,BRAIN physiology ,REGENERATION (Biology) ,GLIOSIS ,SYNAPSES ,PHYSIOLOGY - Abstract
The brains of teleost fish show extensive adult neurogenesis and neuronal regeneration. The patterns of gene regulation during fish brain aging are unknown. The short-lived teleost fish Nothobranchius furzeri shows markers of brain aging including reduced learning performances, gliosis, and reduced adult neurogenesis. We used RNA-seq to quantify genome-wide transcript regulation and sampled five different time points to characterize whole-genome transcript regulation during brain aging of N. furzeri. Comparison with human datasets revealed conserved up-regulation of ribosome, lysosome, and complement activation and conserved down-regulation of synapse, mitochondrion, proteasome, and spliceosome. Down-regulated genes differ in their temporal profiles: neurogenesis and extracellular matrix genes showed rapid decay, synaptic and axonal genes a progressive decay. A substantial proportion of differentially expressed genes (~40%) showed inversion of their temporal profiles in the last time point: spliceosome and proteasome showed initial down-regulation and stress-response genes initial up-regulation. Extensive regulation was detected for chromatin remodelers of the DNMT and CBX families as well as members of the polycomb complex and was mirrored by an up-regulation of the H3K27me3 epigenetic mark. Network analysis showed extensive coregulation of cell cycle/ DNA synthesis genes with the uncharacterized zinc-finger protein ZNF367 as central hub. In situ hybridization showed that ZNF367 is expressed in neuronal stem cell niches of both embryonic zebrafish and adult N. furzeri. Other genes down-regulated with age, not previously associated with adult neurogenesis and with similar patterns of expression are AGR2, DNMT3A, KRCP, MEX3A, SCML4, and CBX1. CBX7, on the other hand, was up-regulated with age. [ABSTRACT FROM AUTHOR]
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- 2014
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6. Epigenetic mechanisms of hyperglycemic memory.
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Cencioni, Chiara, Spallotta, Francesco, Greco, Simona, Martelli, Fabio, Zeiher, Andreas M., and Gaetano, Carlo
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EPIGENETICS , *HYPERGLYCEMIA , *DIABETES complications , *BLOOD sugar , *MOLECULAR structure of chromatin , *GENE expression - Abstract
Highlights: [•] Diabetic complications progress even after blood glucose control is therapeutically achieved. [•] The epigenetic machinery regulates chromatin structure, synchronizing metabolic information with gene expression. [•] Persisting epigenetic marks keep memory of previous transient hyperglycemic events. [•] Epidrugs may represent a potential novel therapeutic option for diabetic patients. [ABSTRACT FROM AUTHOR]
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- 2014
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7. Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases.
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Cencioni, Chiara, Spallotta, Francesco, Martelli, Fabio, Valente, Sergio, Mai, Antonello, Zeiher, Andreas M., and Gaetano, Carlo
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OXIDATIVE stress , *AGE factors in disease , *EPIGENETICS , *PHYSIOLOGICAL aspects of aging , *LIFESTYLES & health , *PATHOLOGICAL physiology - Abstract
Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined "ageing epigenome". The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies. [ABSTRACT FROM AUTHOR]
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- 2013
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8. Pillars and Gaps of S-Nitrosylation-Dependent Epigenetic Regulation in Physiology and Cancer.
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Salvatori, Luisa, Spallotta, Francesco, Gaetano, Carlo, and Illi, Barbara
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NITRIC-oxide synthases , *PHYSIOLOGY , *EPIGENETICS , *AMINO acid metabolism , *GENE expression , *GENETIC regulation - Abstract
Nitric oxide (NO) is a diffusible signaling molecule produced by three isoforms of nitric oxide synthase, which release NO during the metabolism of the amino acid arginine. NO participates in pathophysiological responses of many different tissues, inducing concentration-dependent effect. Indeed, while low NO levels generally have protective effects, higher NO concentrations induce cytotoxic/cytostatic actions. In recent years, evidences have been accumulated unveiling S-nitrosylation as a major NO-dependent post-translational mechanism ruling gene expression. S-nitrosylation is a reversible, highly regulated phenomenon in which NO reacts with one or few specific cysteine residues of target proteins generating S-nitrosothiols. By inducing this chemical modification, NO might exert epigenetic regulation through direct effects on both DNA and histones as well as through indirect actions affecting the functions of transcription factors and transcriptional co-regulators. In this light, S-nitrosylation may also impact on cancer cell gene expression programs. Indeed, it affects different cell pathways and functions ranging from the impairment of DNA damage repair to the modulation of the activity of signal transduction molecules, oncogenes, tumor suppressors, and chromatin remodelers. Nitrosylation is therefore a versatile tool by which NO might control gene expression programs in health and disease. [ABSTRACT FROM AUTHOR]
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- 2021
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9. NO points to epigenetics in vascular development.
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Illi, Barbara, Colussi, Claudia, Rosati, Jessica, Spallotta, Francesco, Nanni, Simona, Farsetti, Antonella, Capogrossi, Maurizio C., and Gaetano, Carlo
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NUCLEOTIDE sequence ,NITRIC oxide ,GENE targeting ,BLOOD-vessel development ,CARDIOVASCULAR diseases ,CELL differentiation ,LINEAGE - Abstract
Our understanding of epigenetic mechanisms important for embryonic vascular development and cardiovascular differentiation is still in its infancy. Although molecular analyses, including massive genome sequencing and/or in vitro/in vivo targeting of specific gene sets, has led to the identification of multiple factors involved in stemness maintenance or in the early processes of embryonic layers specification, very little is known about the epigenetic commitment to cardiovascular lineages. The object of this review will be to outline the state of the art in this field and trace the perspective therapeutic consequences of studies aimed at elucidating fundamental epigenetic networks. Special attention will be paid to the emerging role of nitric oxide in this field. [ABSTRACT FROM AUTHOR]
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- 2011
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10. Enhancement of lysine acetylation accelerates wound repair.
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Spallotta, Francesco, Cencioni, Chiara, Straino, Stefania, Sbardella, Gianluca, Castellano, Sabrina, Capogrossi, Maurizio C., Martelli, Fabio, and Gaetano, Carlo
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WOUND healing , *SIRTUINS , *HISTONE deacetylase inhibitors , *KERATINOCYTES , *NITRIC oxide , *ACETYLATION , *TUBULINS , *LYSINE - Abstract
In physiopathological conditions, such as diabetes, wound healing is significantly compromised and chronic complications, including ulcers, may occur. In a mouse model of skin repair, we recently reported that wound treatment with Sirtuin activators and class I HDAC inhibitors induced keratinocyte proliferation and enhanced healing via a nitric oxide (NO) dependent mechanism. We observed an increase in total protein acetylation in the wound area, as determined by acetylation of α-tubulin and histone H3 Lysine 9. We reasoned that this process activated cell function as well as regulated gene expression to foster tissue repair. We report here that the direct activation of P300/CBP-associated factor (PCAF) by the histone acetylase activator pentadecylidenemalonate 1b (SPV-106) induced Lysine acetylation in the wound area. This intervention was sufficient to enhance repair process by a NO-independent mechanism. Hence, an impairment of PCAF and/or other GCN5 family acetylases may delay skin repair in physiopathological conditions. [ABSTRACT FROM AUTHOR]
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- 2013
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11. The double life of cardiac mesenchymal cells: Epimetabolic sensors and therapeutic assets for heart regeneration.
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Cencioni, Chiara, Atlante, Sandra, Savoia, Matteo, Martelli, Fabio, Farsetti, Antonella, Capogrossi, Maurizio C., Zeiher, Andreas M., Gaetano, Carlo, and Spallotta, Francesco
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CARDIAC regeneration , *MESENCHYMAL stem cells , *DIABETES risk factors , *AGE factors in disease , *BIOSENSORS , *HEART fibrosis - Abstract
Organ-specific mesenchymal cells naturally reside in the stroma, where they are exposed to some environmental variables affecting their biology and functions. Risk factors such as diabetes or aging influence their adaptive response. In these cases, permanent epigenetic modifications may be introduced in the cells with important consequences on their local homeostatic activity and therapeutic potential. Numerous results suggest that mesenchymal cells, virtually present in every organ, may contribute to tissue regeneration mostly by paracrine mechanisms. Intriguingly, the heart is emerging as a source of different cells, including pericytes, cardiac progenitors, and cardiac fibroblasts. According to phenotypic, functional, and molecular criteria, these should be classified as mesenchymal cells. Not surprisingly, in recent years, the attention on these cells as therapeutic tools has grown exponentially, although only very preliminary data have been obtained in clinical trials to date. In this review, we summarized the state of the art about the phenotypic features, functions, regenerative properties, and clinical applicability of mesenchymal cells, with a particular focus on those of cardiac origin. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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12. Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health
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Sandra Atlante, Carlo Gaetano, Johanna Heid, Andreas M. Zeiher, Alessandro Cellerino, Antonella Farsetti, Stefan Guenther, Giulio Pompilio, Francesco Spallotta, Chiara Cencioni, Giuseppina Milano, Giacomo Rossi, Fabio Martelli, Alessandro Scopece, Thomas Braun, Valerio Azzimato, Mario Baumgart, Roberto Ripa, Carsten Kuenne, Heid, Johanna, Cencioni, Chiara, Ripa, Roberto, Baumgart, Mario, Atlante, Sandra, Milano, Giuseppina, Scopece, Alessandro, Kuenne, Carsten, Guenther, Stefan, Azzimato, Valerio, Farsetti, Antonella, Rossi, Giacomo, Braun, Thoma, Pompilio, Giulio, Martelli, Fabio, Zeiher, Andreas M, Cellerino, Alessandro, Gaetano, Carlo, and Spallotta, Francesco
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0301 basic medicine ,Aging ,lcsh:Medicine ,Cell biology ,Cardiovascular biology ,medicine.disease_cause ,Settore BIO/09 - Fisiologia ,fibroblast ,Muscle hypertrophy ,Transcriptome ,0302 clinical medicine ,Fibrosis ,lcsh:Science ,Zebrafish ,Multidisciplinary ,biology ,microRNA ,cardiovascular ,Fishes ,epigenetics ,Heart ,5-Methylcytosine/metabolism ,Animals ,Antagomirs/metabolism ,Cell Hypoxia ,Cell Line ,Collagen/metabolism ,DNA Methylation ,Echocardiography ,Fibroblasts/cytology ,Fibroblasts/metabolism ,Fishes/genetics ,Heart/physiology ,Humans ,MicroRNAs/antagonists & inhibitors ,MicroRNAs/genetics ,MicroRNAs/metabolism ,Myocardium/metabolism ,Oxidative Stress ,Up-Regulation ,5-Methylcytosine ,Collagen ,Cardiac function curve ,medicine.medical_specialty ,Article ,03 medical and health sciences ,Downregulation and upregulation ,Internal medicine ,medicine ,Myocardium ,lcsh:R ,Antagomirs ,Fibroblasts ,medicine.disease ,biology.organism_classification ,MicroRNAs ,030104 developmental biology ,Endocrinology ,lcsh:Q ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12–21 week (adult) and 28–40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5´methyl-cytosine (5mC) level decrease. To further investigate miR-29 family role in the fish heart we generated a transgenic zebrafish model where miR-29 was knocked-down. In this model we found significant morphological and functional cardiac alterations and an impairment of oxygen dependent pathways by transcriptome analysis leading to hypoxic marker up-regulation. To get insights the possible hypoxic regulation of miR-29 family, we exposed human cardiac fibroblasts to 1% O2 levels. In hypoxic condition we found miR-29 down-modulation responsible for the accumulation of collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation might represent an endogenous mechanism aimed at ameliorating the age-dependent cardiac damage leading to hypertrophy and fibrosis.
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- 2017
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