390 results on '"D'ONOFRIO, NUNZIA"'
Search Results
102. Sirtuins in vascular diseases: Emerging roles and therapeutic potential
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D'Onofrio N, Vitiello M, Casale R, SERVILLO, Luigi, GIOVANE, Alfonso, BALESTRIERI, Maria Luisa, D'ONOFRIO, NUNZIA, D'Onofrio, N, Vitiello, M, Casale, R, Servillo, Luigi, Giovane, Alfonso, Balestrieri, Maria Luisa, and D'Onofrio, Nunzia
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Endothelial progenitor cell ,Sirtuin ,Endothelium ,Cardiovascular disease ,Vascular dysfunction - Abstract
Silent information regulator-2 (Sir-2) proteins, or sirtuins, are a highly conserved protein family of histone deacetylases that promote longevity by mediating many of the beneficial effects of calorie restriction which extends life span and reduces the incidence of cancer, cardiovascular disease (CVD), and diabetes. Here, we review the role of sirtuins (SIRT1-7) in vascular homeostasis and diseases by providing an update on the latest knowledge about their roles in endothelial damage and vascular repair mechanisms. Among all sirtuins, in the light of the numerous functions reported on SIRT1 in the vascular system, herein we discuss its roles not only in the control of endothelial cells (EC) functionality but also in other cell types beyond EC, including endothelial progenitor cells (EPC), smooth muscle cells (SMC), and immune cells. Furthermore, we also provide an update on the growing field of compounds under clinical evaluation for the modulation of SIRT1 which, at the state of the art, represents the most promising target for the development of novel drugs against CVD, especially when concomitant with type 2 diabetes
- Published
- 2015
103. Sirtuin 6 expression and inflammatory activity in diabetic atherosclerotic plaques: Effects of incretin treatment. Diabetes 2015;64:1395-1406
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Balestrieri M. L., Rizzo M. R., Barbieri M., Paolisso P., D'Onofrio N., Giovane A., Servillo L., Paolisso G., Marfella R., D'ONOFRIO, NUNZIA, Balestrieri, M. L., Rizzo, M. R., Barbieri, M., Paolisso, P., D'Onofrio, N., Giovane, A., Servillo, L., Paolisso, G., Marfella, R., and D'Onofrio, Nunzia
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Carotid Arterie ,Male ,Diabetes Mellitus, Type 2 ,Dipeptidyl-Peptidase IV Inhibitor ,Receptors, Glucagon ,Sirtuins ,Female ,Incretin ,Plaque, Atherosclerotic ,Human - Published
- 2015
104. ROS-Mediated Apoptotic Cell Death of Human Colon Cancer LoVo Cells by Milk δ-Valerobetaine.
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D'Onofrio, Nunzia, Cacciola, Nunzio Antonio, Martino, Elisa, Borrelli, Francesca, Fiorino, Ferdinando, Lombardi, Assunta, Neglia, Gianluca, Balestrieri, Maria Luisa, and Campanile, Giuseppe
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CELL death , *METABOLITES , *ANTIOXIDANTS , *COLON cancer , *CELL survival , *PROTEIN expression , *AUTOPHAGY - Abstract
δ-Valerobetaine (δVB) is a constitutive milk metabolite with antioxidant and anti-inflammatory activities. Here, we tested the antineoplastic properties of milk δVB on human colorectal cancer cells. CCD 841 CoN (non-tumorigenic), HT-29 (p53 mutant adenocarcinoma) and LoVo (APC/RAS mutant adenocarcinoma) cells were exposed to 3 kDa milk extract, δVB (2 mM) or milk+δVB up to 72 h. Results showed a time- and dose-dependent capability of δVB to inhibit cancer cell viability, with higher potency in LoVo cells. Treatment with milk+δVB arrested cell cycle in G2/M and SubG1 phases by upregulating p21, cyclin A, cyclin B1 and p53 protein expressions. Noteworthy, δVB also increased necrosis (P < 0.01) and when used in combination with milk it improved its activity on live cell reduction (P < 0.05) and necrosis (P < 0.05). δVB-enriched milk activated caspase 3, caspase 9, Bax/Bcl-2 apoptotic pathway and reactive oxygen species (ROS) production, whereas no effects on ROS generation were observed in CCD 841 CoN cells. The altered redox homeostasis induced by milk+δVB was accompanied by upregulation of sirtuin 6 (SIRT6). SIRT6 silencing by small interfering RNA blocked autophagy and apoptosis activated by milk+δVB, unveiling the role of this sirtuin in the ROS-mediated apoptotic LoVo cell death. [ABSTRACT FROM AUTHOR]
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- 2020
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105. MicroRNA‐33 and SIRT1 influence the coronary thrombus burden in hyperglycemic STEMI patients.
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D'Onofrio, Nunzia, Sardu, Celestino, Paolisso, Pasquale, Minicucci, Fabio, Gragnano, Felice, Ferraraccio, Franca, Panarese, Iacopo, Scisciola, Lucia, Mauro, Ciro, Rizzo, Maria Rosaria, Mansueto, Gelsomina, Varavallo, Federica, Brunitto, Giuseppina, Caserta, Rosanna, Tirino, Virginia, Papaccio, Gianpaolo, Barbieri, Michelangela, Paolisso, Giuseppe, Balestrieri, Maria Luisa, and Marfella, Raffaele
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PERCUTANEOUS coronary intervention , *HYPERGLYCEMIA , *MYOCARDIAL infarction , *ENDOTHELIAL cells , *SIRTUINS - Abstract
Primary percutaneous coronary intervention (PPCI) is a pivotal treatment in ST‐segment elevation myocardial infarction (STEMI) patients. However, in hyperglycemic‐STEMI patients, the incidence of death is still significant. Here, the involvement of sirtuin 1 (SIRT1) and miR33 on the pro‐inflammatory/pro‐coagulable state of the coronary thrombus was investigated. Moreover, 1‐year outcomes in hyperglycemic STEMI in patients subjected to thrombus aspiration before PPCI were evaluated. Results showed that hyperglycemic thrombi displayed higher size and increased miR33, reactive oxygen species, and pro‐inflammatory/pro‐coagulable markers. Conversely, the hyperglycemic thrombi showed a lower endothelial SIRT1 expression. Moreover, in vitro experiments on endothelial cells showed a causal effect of SIRT1 modulation on the pro‐inflammatory/pro‐coagulative state via hyperglycemia‐induced miR33 expression. Finally, SIRT1 expression negatively correlated with STEMI outcomes. These observations demonstrate the involvement of the miR33/SIRT1 pathway in the increased pro‐inflammatory and pro‐coagulable state of coronary thrombi in hyperglycemic STEMI patients. [ABSTRACT FROM AUTHOR]
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- 2020
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106. Inflammatory Cytokines and SIRT1 Levels in Subcutaneous Abdominal Fat: Relationship With Cardiac Performance in Overweight Pre-diabetics Patients
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Sardu, Celestino, primary, Pieretti, Gorizio, additional, D'Onofrio, Nunzia, additional, Ciccarelli, Feliciano, additional, Paolisso, Pasquale, additional, Passavanti, Maria B., additional, Marfella, Raffaele, additional, Cioffi, Michele, additional, Mone, Pasquale, additional, Dalise, Anna M., additional, Ferraraccio, Franca, additional, Panarese, Iacopo, additional, Gambardella, Antonio, additional, Passariello, Nicola, additional, Rizzo, Maria R., additional, Balestrieri, Maria L., additional, Nicoletti, Gianfranco, additional, and Barbieri, Michelangela, additional
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- 2018
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107. Carnitine Precursors and Short-Chain Acylcarnitines in Water Buffalo Milk
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Servillo, Luigi, primary, D’Onofrio, Nunzia, additional, Neglia, Gianluca, additional, Casale, Rosario, additional, Cautela, Domenico, additional, Marrelli, Massimo, additional, Limone, Antonio, additional, Campanile, Giuseppe, additional, and Balestrieri, Maria Luisa, additional
- Published
- 2018
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108. Ophthalmic acid is a marker of oxidative stress in plants as in animals
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Servillo, Luigi, primary, Castaldo, Domenico, additional, Giovane, Alfonso, additional, Casale, Rosario, additional, D'Onofrio, Nunzia, additional, Cautela, Domenico, additional, and Balestrieri, Maria Luisa, additional
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- 2018
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109. SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection
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D'Onofrio, Nunzia, primary, Servillo, Luigi, additional, and Balestrieri, Maria Luisa, additional
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- 2018
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110. Vascular-homing peptides for targeted drug delivery and molecular imaging: meeting the clinical challenges
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D'Onofrio N, CARAGLIA, Michele, Grimaldi A, MARFELLA, Raffaele, SERVILLO, Luigi, PAOLISSO, Giuseppe, BALESTRIERI, Maria Luisa, D'ONOFRIO, NUNZIA, D'Onofrio, N, Caraglia, Michele, Grimaldi, A, Marfella, Raffaele, Servillo, Luigi, Paolisso, Giuseppe, Balestrieri, Maria Luisa, and D'Onofrio, Nunzia
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Cancer Research ,Phage display ,Angiogenesis Inhibitors ,Diagnostic tools ,Bioinformatics ,Drug Delivery Systems ,In vivo ,Peptide Library ,Drug Discovery ,Genetics ,Medicine ,Animals ,Humans ,Molecular Targeted Therapy ,Peptide ligand ,Neovascularization, Pathologic ,business.industry ,Tumor endothelial cell ,Molecular Imaging ,Oncology ,Targeted drug delivery ,Immunology ,Endothelium, Vascular ,Molecular imaging ,business ,Peptides ,Homing (hematopoietic) - Abstract
The vasculature of each organ expresses distinct molecular signatures critically influenced by the pathological status. The heterogeneous profile of the vascular beds has been successfully unveiled by the in vivo phage display, a high-throughput tool for mapping normal, diseased, and tumor vasculature. Specific challenges of this growing field are targeted therapies against cancer and cardiovascular diseases, as well as novel bioimaging diagnostic tools. Tumor vasculature-homing peptides have been extensively evaluated in several preclinical and clinical studies both as targeted-therapy and diagnosis. To date, results from several Phase I and II trials have been reported and many other trials are currently ongoing or recruiting patients. In this review, advances in the identification of novel peptide ligands and their corresponding receptors on tumor endothelium through the in vivo phage display technology are discussed. Emphasis is given to recent findings in the clinical setting of vascular-homing peptides selected by in vivo phage display for the treatment of advanced malignancies and their altered vascular beds.
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- 2014
111. N-methylated derivatives of tyramine in citrus genus plants: identification of N,N,N-trimethyltyramine (candicine)
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SERVILLO, Luigi, GIOVANE, Alfonso, D'Onofrio N, Casale R, Cautela D, Ferrari G, BALESTRIERI, Maria Luisa, Castaldo D., D'ONOFRIO, NUNZIA, Servillo, Luigi, Giovane, Alfonso, D'Onofrio, N, Casale, R, Cautela, D, Ferrari, G, Balestrieri, Maria Luisa, Castaldo, D., and D'Onofrio, Nunzia
- Published
- 2014
112. Bioavailability of encapsulated resveratrol into nanoemulsion-based delivery systems
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Sessa M, BALESTRIERI, Maria Luisa, Ferrari G, SERVILLO, Luigi, Castaldo D, D'Onofrio N, Donsì F, Tsao R., D'ONOFRIO, NUNZIA, Sessa, M, Balestrieri, Maria Luisa, Ferrari, G, Servillo, Luigi, Castaldo, D, D'Onofrio, N, Donsì, F, Tsao, R., and D'Onofrio, Nunzia
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- 2014
113. Platelet-activating factor mediates the cytotoxicity induced by W7FW14F apomyoglobin amyloid aggregates in neuroblastoma cells
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SIRANGELO, Ivana, GIOVANE, Alfonso, Maritato, R, D'Onofrio, N, IANNUZZI, Clara, Giordano, A, IRACE, Gaetano, BALESTRIERI, Maria Luisa, D'ONOFRIO, NUNZIA, Sirangelo, Ivana, Giovane, Alfonso, Maritato, R, D'Onofrio, N, Iannuzzi, Clara, Giordano, A, Irace, Gaetano, Balestrieri, Maria Luisa, and D'Onofrio, Nunzia
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AMYLOID AGGREGATES ,PAF ,AMYLOID CYTOTOXICITY - Abstract
W7FW14F apomyoglobin (W7FW14F ApoMb) amyloid aggregates induce cytotoxicity in SH-SY5Y human neuroblastoma cells through a mechanism not fully elucidated. Amyloid neurotoxicity process involves calcium dyshomeostasis and reactive oxygen species (ROS) production. Another key mediator of the amyloid neurotoxicity is Platelet-Activating Factor (PAF), an inflammatory phospholipid implicated in neurodegenerative diseases. Here, with the aim at evaluating the possible involvement of PAF signaling in the W7FW14F ApoMb-induced cytotoxicity, we show that the presence of CV3899, a PAF receptor (PAF-R) antagonist, prevented the detrimental effect of W7FW14F ApoMb aggregates on SH-SY5Y cell viability. Noticeably, we found that the activation of PAF signaling, following treatment with W7FW14F ApoMb, involves a decreased expression of the PAF acetylhydroase II (PAF-AH II). Interestingly, the reduced PAF-AH II expression was associated with a decreased acetylhydrolase (AH) activity and to an increased sphingosine-transacetylase activity (TAS) with production of N-acetylsphingosine (C2-ceramide), a well known mediator of neuronal caspase-dependent apoptosis. These findings suggest that an altered PAF catabolism takes part to the molecular events leading to W7FW14F ApoMb amyloid aggregates-induced cell death
- Published
- 2014
114. Gaba-betaine modulates SIRT1 and p16INK4A expression during high-glucose induced endothelial cell senescence
- Author
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D’Onofrio, Nunzia, primary, Servillo, Luigi, additional, Giovane, Alfonso, additional, Casale, Rosario, additional, Cautela, Domenico, additional, Castaldo, Domenico, additional, and Balestrieri, Maria Luisa, additional
- Published
- 2017
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115. Multiple pathways of SIRT6 at the crossroads in the control of longevity, cancer, and cardiovascular diseases
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Vitiello, Milena, primary, Zullo, Alberto, additional, Servillo, Luigi, additional, Mancini, Francesco Paolo, additional, Borriello, Adriana, additional, Giovane, Alfonso, additional, Della Ragione, Fulvio, additional, D’Onofrio, Nunzia, additional, and Balestrieri, Maria Luisa, additional
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- 2017
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116. Tyramine Pathways in Citrus Plant Defense: Glycoconjugates of Tyramine and Its N-Methylated Derivatives
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Servillo, Luigi, primary, Castaldo, Domenico, additional, Giovane, Alfonso, additional, Casale, Rosario, additional, D’Onofrio, Nunzia, additional, Cautela, Domenico, additional, and Balestrieri, Maria Luisa, additional
- Published
- 2017
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117. Glucosylated forms of serotonin and tryptophan in green coffee beans
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Servillo, Luigi, primary, Giovane, Alfonso, additional, Casale, Rosario, additional, Cautela, Domenico, additional, D’Onofrio, Nunzia, additional, Balestrieri, Maria Luisa, additional, and Castaldo, Domenico, additional
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- 2016
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118. Determination of homoarginine, arginine, NMMA, ADMA, and SDMA in biological samples by HPLC-ESI-mass spectrometry
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SERVILLO, Luigi, GIOVANE, Alfonso, D'Onofrio N, Casale R, Cautela D, Castaldo D, BALESTRIERI, Maria Luisa, D'ONOFRIO, NUNZIA, Servillo, Luigi, Giovane, Alfonso, D'Onofrio, N, Casale, R, Cautela, D, Castaldo, D, Balestrieri, Maria Luisa, and D'Onofrio, Nunzia
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- 2013
119. Stachydrine ameliorates high-glucose induced endothelial cell senescence and SIRT1 downregulation
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SERVILLO, Luigi, D'Onofrio N, Longobardi L, SIRANGELO, Ivana, GIOVANE, Alfonso, Cautela D, Castaldo D, Giordano A, BALESTRIERI, Maria Luisa, D'ONOFRIO, NUNZIA, Servillo, Luigi, D'Onofrio, N, Longobardi, L, Sirangelo, Ivana, Giovane, Alfonso, Cautela, D, Castaldo, D, Giordano, A, Balestrieri, Maria Luisa, and D'Onofrio, Nunzia
- Published
- 2013
120. Poor glycaemic control in type 2 diabetes patients impairs endothelial progenitor cell number by influencing SIRT1 signaling via Platelet-Activating Factor receptor activation
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BALESTRIERI, Maria Luisa, SERVILLO, Luigi, ESPOSITO A, D’ONOFRIO N, GIOVANE, Alfonso, CASALE R, BARBIERI, Michelangela, PAOLISSO P, RIZZO, Maria Rosaria, PAOLISSO, Giuseppe, MARFELLA, Raffaele, D'ONOFRIO, NUNZIA, Balestrieri, Maria Luisa, Servillo, Luigi, Esposito, A, D’Onofrio, N, Giovane, Alfonso, Casale, R, Barbieri, Michelangela, Paolisso, P, Rizzo, Maria Rosaria, Paolisso, Giuseppe, Marfella, Raffaele, and D'Onofrio, Nunzia
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Adult ,Male ,medicine.medical_specialty ,Endothelium ,Endocrinology, Diabetes and Metabolism ,Down-Regulation ,Cell Count ,Cell Separation ,Platelet Membrane Glycoproteins ,Biology ,Endothelial progenitor cell ,Receptors, G-Protein-Coupled ,chemistry.chemical_compound ,Sirtuin 1 ,Downregulation and upregulation ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Glucose homeostasis ,RNA, Messenger ,Progenitor cell ,Receptor ,Cells, Cultured ,Aged ,Platelet-activating factor ,Phospholipid Ethers ,Middle Aged ,Adult Stem Cells ,Endocrinology ,medicine.anatomical_structure ,Diabetes Mellitus, Type 2 ,chemistry ,Hyperglycemia ,Blood Buffy Coat ,cardiovascular system ,Female ,lipids (amino acids, peptides, and proteins) ,Endothelium, Vascular ,Platelet-activating factor receptor ,Diabetic Angiopathies ,Platelet Aggregation Inhibitors ,Signal Transduction - Abstract
Downregulation of levels of endothelial progenitor cells (EPCs) during in-vitro short-term exposure to high glucose concentrations relates to reduced activity of silent information regulator 1 (SIRT1) and increased synthesis of platelet-activating factor (PAF). We investigated the possible relationship between PAF and SIRT1 pathways in EPCs during altered glucose homeostasis.SIRT1 and PAF receptor (PAF-R) levels were determined by western blot, RT-PCR and confocal laser-scanning microscopy. In-vivo experiments were performed on 48 type 2 diabetic patients (25 with poor glycaemic control and 23 with good glycaemic control) and 20 control individuals. In-vitro experiments with the PAF-R antagonist CV3988 were performed on EPCs isolated from leucocyte-rich buffy coat of healthy human donors.Decreased SIRT1 protein levels were observed in EPCs from type 2 diabetic patients compared with control individuals (p0.01). Notably, the SIRT1 level was consistently lower in patients with poor glycaemic control than in those with good glycaemic control (p0.01). Diabetic patients also showed an upregulation of PAF-Rs; this response occurred to a greater extent in individuals with poor glycaemic control than in those with good glycaemic control. In-vitro experiments confirmed that EPCs respond to PAF stimulation with decreased SIRT1 protein and SIRT1 mRNA levels. Moreover, reduction of SIRT1 levels and activity were abolished by CV3988.These findings unveil a link between PAF and SIRT1 pathways in EPCs that contributes to the deleterious effect of hyperglycaemia on the functional properties of EPCs, crucial in diabetes and peripheral vascular complications.
- Published
- 2013
121. The synergistic effect of everolimus and chloroquine on endothelial cell number reduction is paralleled by increased apoptosis and reduced autophagy occurrence
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Grimaldi A, BALESTRIERI, Maria Luisa, D'Onofrio N, Di Domenico G, Nocera C, LAMBERTI, Monica, Tonini G, Zoccoli A, Santini D, CARAGLIA, Michele, Pantano F., D'ONOFRIO, NUNZIA, Grimaldi, A, Balestrieri, Maria Luisa, D'Onofrio, N, Di Domenico, G, Nocera, C, Lamberti, Monica, Tonini, G, Zoccoli, A, Santini, D, Caraglia, Michele, Pantano, F., and D'Onofrio, Nunzia
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Programmed cell death ,Cell Survival ,Angiogenesis ,lcsh:Medicine ,Apoptosis ,Cell Count ,Pharmacology ,Biology ,Models, Biological ,chemistry.chemical_compound ,Autophagy ,medicine ,Humans ,Everolimus ,Progenitor cell ,lcsh:Science ,Cell Proliferation ,Sirolimus ,Multidisciplinary ,Stem Cells ,lcsh:R ,Endothelial Cells ,Membrane Proteins ,Chloroquine ,Drug Synergism ,Endothelial stem cell ,Proto-Oncogene Proteins c-bcl-2 ,chemistry ,Cancer cell ,cardiovascular system ,Beclin-1 ,lcsh:Q ,Growth inhibition ,Apoptosis Regulatory Proteins ,Research Article ,medicine.drug - Abstract
"Endothelial Progenitor Cells (EPCs), a minor subpopulation of the mononuclear cell fraction in peripheral blood, play a critical role in cancer development as they contribute to angiogenesis-mediated pathological neovascularization. In response to tumor cytokines, including VEGF, EPCs mobilize from the bone marrow into the peripheral circulation and move to the tumor bed where they incorporate into sprouting neovessels. In the present study, we evaluated the effects of everolimus (Afinitor, Novartis), a rapamycin analogue, alone or in combination with chloroquine, a 4-alkylamino substituted quinoline family member, one of the autophagy inhibitors, on EPCs biological functions. We found that either everolimus or chloroquine induce growth inhibition on EPCs in a dose-dependent manner after 72 h from the beginning of incubation. The combined administration of the two drugs to EPC was synergistic in inducing growth inhibition; in details, the maximal pharmacological synergism between everolimus and chloroquine in inducing growth inhibition on EPCs cells was recorded when chloroquine was administered 24 h before everolimus. Moreover, we have studied the mechanisms of cell death induced by the two agents alone or in combination on EPCs and we have found that the synergistic effect of combination on EPC growth inhibition was paralleled by increased apoptosis induction and reduced autophagy. These effects occurred together with biochemical features that are typical of reduced autophagic death such as increased co-immunoprecipitation between Beclin 1 and Bcl-2. Chloroquine antagonized the inhibition of the activity of Akt→4EBP1 axis mediated by everolimus and at the same time it blocked the feed-back activation of Erk-1\/2 induced by RAD in EPCs. These data suggest a new strategy in order to block angiogenesis in tumours in which this process plays a key role in both the sustainment and spreading of cancer cells"
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- 2013
122. Occurrence and Analysis of Betaines in Fruits
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Servillo, Luigi, Giovane, Alfonso, Casale, Rosario, D'Onofrio, Nunzia, Ferrari, Giovanna, Cautela, Domenico, Castaldo, Domenico, and Balestrieri, Maria Luisa
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Food Science ,Analytical Chemistry - Published
- 2015
123. Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6
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D’Onofrio, Nunzia, primary, Servillo, Luigi, additional, Giovane, Alfonso, additional, Casale, Rosario, additional, Vitiello, Milena, additional, Marfella, Raffaele, additional, Paolisso, Giuseppe, additional, and Balestrieri, Maria Luisa, additional
- Published
- 2016
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124. Sirtuins in vascular diseases: Emerging roles and therapeutic potential
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D'Onofrio, Nunzia, primary, Vitiello, Milena, additional, Casale, Rosario, additional, Servillo, Luigi, additional, Giovane, Alfonso, additional, and Balestrieri, Maria Luisa, additional
- Published
- 2015
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125. N-Methylated Derivatives of Tyramine in Citrus Genus Plants: Identification of N,N,N-Trimethyltyramine (Candicine)
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Servillo, Luigi, primary, Giovane, Alfonso, additional, D’Onofrio, Nunzia, additional, Casale, Rosario, additional, Cautela, Domenico, additional, Ferrari, Giovanna, additional, Balestrieri, Maria Luisa, additional, and Castaldo, Domenico, additional
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- 2014
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126. Determination of Homoarginine, Arginine, NMMA, ADMA, and SDMA in Biological Samples by HPLC-ESI-Mass Spectrometry
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Servillo, Luigi, primary, Giovane, Alfonso, additional, D'Onofrio, Nunzia, additional, Casale, Rosario, additional, Cautela, Domenico, additional, Castaldo, Domenico, additional, and Balestrieri, Maria, additional
- Published
- 2013
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127. Stachydrine ameliorates high-glucose induced endothelial cell senescence and SIRT1 downregulation
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Servillo, Luigi, primary, D'Onofrio, Nunzia, additional, Longobardi, Lara, additional, Sirangelo, Ivana, additional, Giovane, Alfonso, additional, Cautela, Domenico, additional, Castaldo, Domenico, additional, Giordano, Antonio, additional, and Balestrieri, Maria Luisa, additional
- Published
- 2013
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128. Sodium/glucose cotransporter 2 (SGLT2) inhibitors improve cardiac function by reducing JunD expression in human diabetic hearts.
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Marfella, Raffaele, D'Onofrio, Nunzia, Trotta, Maria Consiglia, Sardu, Celestino, Scisciola, Lucia, Amarelli, Cristiano, Balestrieri, Maria Luisa, Grimaldi, Vincenzo, Mansueto, Gelsomina, Esposito, Salvatore, D'Amico, Michele, Golino, Paolo, Signoriello, Giuseppe, De Feo, Marisa, Maiello, Ciro, Napoli, Claudio, and Paolisso, Giuseppe
- Subjects
SODIUM-glucose cotransporters ,AP-1 transcription factor ,DIABETIC cardiomyopathy ,HEART diseases ,GLUCOSE ,INSULIN receptors - Abstract
The pathogenesis of experimental diabetic cardiomyopathy may involve the activator protein 1 (AP-1) member, JunD. Using non-diabetic heart transplant (HTX) in recipients with diabetes, we examined the effects of the diabetic milieu (hyperglycemia and insulin resistance) on cardiac JunD expression over 12 months. Because sodium/glucose cotransporter-2 inhibitors (SGLT2i) significantly reverse high glucose-induced AP-1 binding in the proximal tubular cell, we investigated JunD expression in a subgroup of type 2 diabetic recipients receiving SGLT2i treatment. We evaluated 77 first HTX recipients (40 and 37 patients with and without diabetes, respectively). Among the recipients with diabetes, 17 (45.9%) were receiving SGLT2i treatment. HTX recipients underwent standard clinical evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsy). In the biopsy samples, we evaluated JunD, insulin receptor substrates 1 and 2 (IRS1 and IRS2), peroxisome proliferator-activated receptor-γ (PPAR-γ), and ceramide levels using real-time polymerase chain reaction and immunofluorescence. The biopsy evaluations in this study were performed at 1–4 weeks (basal), 5–12 weeks (intermediate), and up to 48 weeks (final, end of 12-month follow-up) after HTX. There was a significant early and progressive increase in the cardiac expression of JunD/PPAR-γ and ceramide levels, along with a significant decrease in IRS1 and IRS2 in recipients with diabetes but not in those without diabetes. These molecular changes were blunted in patients with diabetes receiving SGLT2i treatment. Early pathogenesis in human diabetic cardiomyopathy is associated with JunD/PPAR-γ overexpression and lipid accumulation following HTX in recipients with diabetes. Remarkably, this phenomenon was reduced by concomitant therapy with SGLT2i, which acted directly on diabetic hearts. Potential direct myocardial effects of SGLT2i in human diabetic hearts. [Display omitted] • Molecular mechanisms of heart dysfunction are of the utmost importance in patients with diabetes. • JunD/PPAR-γ pathways in the human diabetic heart may be an attractive therapeutic option. • SGLT2i reduces JunD/PPAR-γ pathway activity to improve heart function in patients with diabetes. [ABSTRACT FROM AUTHOR]
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- 2022
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129. Transcriptomic profiles of the ruminal wall in Italian Mediterranean dairy buffaloes fed green forage.
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Salzano, Angela, Fioriniello, Salvatore, D'Onofrio, Nunzia, Balestrieri, Maria Luisa, Aiese Cigliano, Riccardo, Neglia, Gianluca, Della Ragione, Floriana, and Campanile, Giuseppe
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CALCIUM metabolism , *HOMEOSTASIS , *AMINO acid metabolism , *TRANSCRIPTOMES , *LIPID metabolism , *MILK quality , *GENE ontology - Abstract
Background: Green feed diet in ruminants exerts a beneficial effect on rumen metabolism and enhances the content of milk nutraceutical quality. At present, a comprehensive analysis focused on the identification of genes, and therefore, biological processes modulated by the green feed in buffalo rumen has never been reported. We performed RNA-sequencing in the rumen of buffaloes fed a total mixed ration (TMR) + the inclusion of 30% of ryegrass green feed (treated) or TMR (control), and identified differentially expressed genes (DEGs) using EdgeR and NOISeq tools. Results: We found 155 DEGs using EdgeR (p-values < 0.05) and 61 DEGs using NOISeq (prob ≥0.8), 30 of which are shared. The rt-qPCR validation suggested a higher reliability of EdgeR results as compared with NOISeq data, in our biological context. Gene Ontology analysis of DEGs identified using EdgeR revealed that green feed modulates biological processes relevant for the rumen physiology and, then, health and well-being of buffaloes, such as lipid metabolism, response to the oxidative stress, immune response, and muscle structure and function. Accordingly, we found: (i) up-regulation of HSD17B13, LOC102410803 (or PSAT1) and HYKK, and down-regulation of CDO1, SELENBP1 and PEMT, encoding factors involved in energy, lipid and amino acid metabolism; (ii) enhanced expression of SIM2 and TRIM14, whose products are implicated in the immune response and defense against infections, and reduced expression of LOC112585166 (or SAAL1), ROR2, SMOC2, and S100A11, encoding pro-inflammatory factors; (iii) up-regulation of NUDT18, DNAJA4 and HSF4, whose products counteract stressful conditions, and down-regulation of LOC102396388 (or UGT1A9) and LOC102413340 (or MRP4/ABCC4), encoding detoxifying factors; (iv) increased expression of KCNK10, CACNG4, and ATP2B4, encoding proteins modulating Ca2+ homeostasis, and reduced expression of the cytoskeleton-related MYH11 and DES. Conclusion: Although statistically unpowered, this study suggests that green feed modulates the expression of genes involved in biological processes relevant for rumen functionality and physiology, and thus, for welfare and quality production in Italian Mediterranean dairy buffaloes. These findings, that need to be further confirmed through the validation of additional DEGs, allow to speculate a role of green feed in the production of nutraceutical molecules, whose levels might be enhanced also in milk. [ABSTRACT FROM AUTHOR]
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- 2023
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130. SGLT-2 inhibitors and in-stent restenosis-related events after acute myocardial infarction: an observational study in patients with type 2 diabetes.
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Marfella, Raffaele, Sardu, Celestino, D'Onofrio, Nunzia, Fumagalli, Carlo, Scisciola, Lucia, Sasso, Ferdinando Carlo, Siniscalchi, Mario, Marfella, Ludovica Vittoria, D'Andrea, Davide, Minicucci, Fabio, Signoriello, Giuseppe, Cesaro, Arturo, Trotta, Maria Consiglia, Frigé, Chiara, Prattichizzo, Francesco, Balestrieri, Maria Luisa, Ceriello, Antonio, Calabrò, Paolo, Mauro, Ciro, and del Viscovo, Luca
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MYOCARDIAL infarction , *TYPE 2 diabetes , *CANAGLIFLOZIN , *MAJOR adverse cardiovascular events , *DAPAGLIFLOZIN , *GLYCEMIC control , *PERCUTANEOUS coronary intervention - Abstract
Background: No study evaluated the incidence of intra-stent restenosis (ISR)-related events in patients with type 2 diabetes (T2DM) and acute myocardial infarction (AMI) treated or not with sodium/glucose cotransporter 2 inhibitors (SGLT2i). Methods: We recruited 377 patients with T2DM and AMI undergoing percutaneous coronary intervention (PCI). Among them, 177 T2DM were treated with SGLT2 inhibitors before PCI. The primary outcome was major adverse cardiovascular events (MACE) defined as cardiac death, re-infarction, and heart failure related to ISR. In patients without ISR, minimal lumen area and minimal lumen diameter were assessed by coronary CT-angiography at 1-year follow-up. Results: Glycemic control was similar in SGLT2i-treated patients and never SGLT2i-users. The incidence of ISR-related MACE was higher in never SGLT2i-users compared with SGLT2i-treated patients, an effect independent of glycemic status (HR = 0.418, 95% CI = 0.241–0.725, P = 0.002) and observed also in the subgroup of patients with HbA1c < 7% (HR = 0.393, 95% CI = 0.157–0.984, P = 0.027). In patients without the event, the stent patency was greater in SGLT2i-treated patients compared with never SGLT2i-users at 1-year follow-up. Conclusions: SGLT2i treatment in T2DM is associated with a reduced incidence of ISR-related events, independently of glycemic control. [ABSTRACT FROM AUTHOR]
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- 2023
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131. Sodium-glucose co-transporter2 expression and inflammatory activity in diabetic atherosclerotic plaques: Effects of sodium-glucose co-transporter2 inhibitor treatment.
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D'Onofrio, Nunzia, Sardu, Celestino, Trotta, Maria Consiglia, Scisciola, Lucia, Turriziani, Fabrizio, Ferraraccio, Franca, Panarese, Iacopo, Petrella, Lella, Fanelli, Mara, Modugno, Piero, Massetti, Massimo, Marfella, Ludovica Vittoria, Sasso, Ferdinando Carlo, Rizzo, Maria Rosaria, Barbieri, Michelangela, Furbatto, Fulvio, Minicucci, Fabio, Mauro, Ciro, Federici, Massimo, and Balestrieri, Maria Luisa
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We evaluated sodium-glucose co-transporter2 (SGLT2) expression and the effect of SGLT2 inhibitor (SGLT2i) therapies on carotid plaques of asymptomatic diabetic and non-diabetic patients. Plaques were obtained from 296 non-diabetic patients and 227 patients with type 2 diabetes undergoing carotid endarterectomy. 97 patients with type 2 diabetes were treated with SGLT2 inhibitors for 16 ± 4 months before endarterectomy. After propensity score matching analysis, patients with type 2 diabetes were categorized without (n = 87) and with SGLT2i therapy (n = 87). To investigate SGLT2 expression levels' effects on major adverse endpoints (MACE = stroke, transient ischemic attack, myocardial infarction, and death), we evaluated MACE outcomes at a 2-year follow-up. Compared to plaques from patients without diabetes, plaques from patients with diabetes had higher SGLT2 expression, inflammation, and oxidative stress, along with lower SIRT6 expression and collagen content. Compared with plaques from patients with diabetes, SGLT2i-treated patients with type 2 diabetes presented increased SIRT6 expression and collagen content and lowered inflammation and ion and oxidative stress, thus indicating a more stable plaque phenotype. These results supported in vitro observations on human aorta endothelial cells (EC) (TeloHAEC-cells). Indeed, EC treated with high glucose (25 mM) in the presence of SGLT2i (100 nM canagliflozin) presented higher SIRT6 expression and decreased mRNA and protein SGLT2 levels, nuclear factor-kappa B (NF- B (NF - κB) , and matrix metallopeptidase 9 (MMP-9) expression compared to cells treated only with high glucose. After two years following endarterectomy, a multivariable Cox regression analysis showed significantly higher 2-year overall survival from MACE in patients without diabetes (P < 0.01). Among patient with diabetes, the current SGLT2i users presented a significantly lower rate of MACE through 2 years compared to non-SGLT2i users (P < 0.05). These findings unveil a critical involvement of the SGLT2/SIRT6 pathway in the inflammatory process of diabetic atherosclerotic lesions and suggest its possible favorable modulation by SGLT2i. • The identification of novel molecular targets of atherosclerosis progression is of utmost importance in diabetic patients. • The occurrence of SGLT2 receptors on the endothelial cells of atherosclerotic plaques may be an attractive therapeutic option for atherosclerosis in patients with diabetes. • SGLT2/SIRT6 represents an attractive option, given its crucial involvement in atherosclerosis progression. • The endothelial SGLT2 inhibition increases the endothelial expression of SIRT6, yielding an improved atherosclerotic plaque phenotype and 2-year outcome. • The impairment of the endothelial SGLT2/SIRT6 pathway worsens outcomes in atherosclerotic patients with diabetes; this may be a potential preventive target. [ABSTRACT FROM AUTHOR]
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- 2021
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132. SIRT3 and Metabolic Reprogramming Mediate the Antiproliferative Effects of Whey in Human Colon Cancer Cells.
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D'Onofrio, Nunzia, Martino, Elisa, Balestrieri, Anna, Mele, Luigi, Neglia, Gianluca, Balestrieri, Maria Luisa, and Campanile, Giuseppe
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COLON tumors , *MILK , *ANTIOXIDANTS , *APOPTOSIS , *DAIRY products , *COLORECTAL cancer , *CELL cycle , *GENE expression , *MITOCHONDRIA , *TRANSFERASES , *CELL proliferation , *WHEY proteins , *CELL lines , *MAMMALS - Abstract
Simple Summary: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths and the most frequently diagnosed cancer type. CRC risk can be preventable by modifiable risk factors, including diet. This study provides evidence on the antiproliferative and pro-apoptotic effects of whey from Mediterranean water buffalo (Bubalus bubalis) milk in HT-29, HCT 116, LoVo, and SW480 cells. Results showed that whey induced metabolic dysfunctions and modulated the bioenergetic signature of CRC cells by targeting SIRT3 expression. These findings unveil the anti-neoplastic effects of whey and pave the way for the use of this by-product, rich in bioactive nutrients, in the setting of novel prevention strategies to reduce the risk of CRC. Emerging strategies to improve healthy aging include dietary interventions as a tool to promote health benefits and reduce the incidence of aging-related comorbidities. The health benefits of milk are also linked to its richness in betaines and short-chain acylcarnitines, which act synergistically in conferring anticancer, anti-inflammatory, and antioxidant properties. Whey, despite being a dairy by-product, still has a considerable content of bioactive betaines and acylcarnitines. Here, we investigated the anticancer properties of whey from Mediterranean water buffalo (Bubalus bubalis) milk by testing its antiproliferative effects in colorectal cancer (CRC) cells HT-29, HCT 116, LoVo and SW480. Results indicated that treatment with whey for 72 h inhibited cell proliferation (p < 0.001), induced cell cycle arrest, and apoptosis via caspase-3 activation, and modulated cell metabolism by limiting glucose uptake and interfering with mitochondrial energy metabolism with the highest effects observed in HT-29 and HCT 116 cells. At molecular level, these effects were accompanied by upregulation of sirtuin 3 (SIRT3) (p < 0.01) and peroxisome proliferator-activated receptor (PPAR)-γ expression (p < 0.001), and downregulation of lactate dehydrogenase A (LDHA) (p < 0.01), sterol regulatory-element binding protein 1 (SREBP1) (p < 0.05), and PPAR-α (p < 0.01). Transient SIRT3 gene silencing blocked the effects of whey on the LDHA, PPAR-γ, and PPAR-α protein expressions (p < 0.01) suggesting that the whey capacity of perturbating the metabolic homeostasis in CRC cell lines is mediated by SIRT3. [ABSTRACT FROM AUTHOR]
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- 2021
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133. Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3.
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D'Onofrio, Nunzia, Martino, Elisa, Mele, Luigi, Colloca, Antonino, Maione, Martina, Cautela, Domenico, Castaldo, Domenico, and Balestrieri, Maria Luisa
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COLORECTAL cancer , *CELL death , *CELL cycle , *COLON cancer , *CANCER invasiveness , *APOPTOSIS - Abstract
Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells. [ABSTRACT FROM AUTHOR]
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- 2021
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134. Phenolic Profiles of Red Wine Relate to Vascular Endothelial Benefits Mediated by SIRT1 and SIRT6.
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D'Onofrio, Nunzia, Martino, Elisa, Chianese, Giuseppina, Coppola, Francesca, Picariello, Luigi, Moio, Luigi, Balestrieri, Maria Luisa, Gambuti, Angelita, and Forino, Martino
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SIRTUINS , *ITALIAN wines , *ANTHOCYANINS , *PLANT polyphenols , *TYPE 2 diabetes , *REACTIVE oxygen species , *OXIDANT status , *RED wines - Abstract
Dietary phenolic compounds possess potent bioactivity against inflammatory pathways of chronic inflammatory conditions, such as type 2 diabetes. Here, the phenolic profile and bioactivity of Italian red wines Gaglioppo, Magliocco, and Nerello Mascalese were characterized. NMR, HPLC/UV-Vis and spectrophotometric characterization showed that Magliocco was the richest wine in monomeric anthocyanins (two-fold), catechins, and low molecular weight phenolics (LMWP). A positive correlation was observed between the polyphenolic content and antioxidant capacity (p < 0.05), with Magliocco displaying the highest antioxidant capacity (p < 0.01). In vitro evidence on the endothelial cell models of insulin resistance and hyperglycemia showed the ability of Magliocco to reduce reactive oxygen species (ROS) (p < 0.01) and cytokine release (p < 0.01) and to upregulate SIRT1 and SIRT6 (p < 0.01). On the whole, the results indicated that the quantitative and qualitative phenolic profiles of red wines influence their in vitro beneficial effects on oxidative and proinflammatory milieu in endothelial cells, showing a positive modulation of SIRT1 and SIRT6, both implied in vascular aging. [ABSTRACT FROM AUTHOR]
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- 2021
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135. Synergistic Effect of Dietary Betaines on SIRT1-Mediated Apoptosis in Human Oral Squamous Cell Carcinoma Cal 27.
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D'Onofrio, Nunzia, Mele, Luigi, Martino, Elisa, Salzano, Angela, Restucci, Brunella, Cautela, Domenico, Tatullo, Marco, Balestrieri, Maria Luisa, and Campanile, Giuseppe
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CELL proliferation , *REACTIVE oxygen species , *ANTINEOPLASTIC agents , *APOPTOSIS , *CELL lines , *DIETARY supplements , *HEAD & neck cancer , *SQUAMOUS cell carcinoma , *TREATMENT effectiveness , *BETAINE , *DESCRIPTIVE statistics , *IN vitro studies , *PHARMACODYNAMICS - Abstract
Simple Summary: Betaines are important human nutrients widely distributed in plants, animals, and dietary sources. δ-valerobetaine (δVB) is a naturally occurring betaine with antioxidant, anti-inflammatory and anticancer activities. The aim of our study was to investigate the possible synergism between δVB and the structurally related γ-butyrobetaine (γBB) by testing the in vitro anticancer activity in head and neck squamous cell carcinomas. Combined δVB and γBB caused a marked inhibition of cell proliferation and induction of apoptosis in Cal 27 cells. The increased reactive oxygen species accumulation influenced the nuclear expression of SIRT1. Gene silencing with small interfering RNA confirmed the role of SIRT1 in the apoptotic cell death. Synergism of δVB and γBB is useful for novel strategies to optimize their content in meat, milk and dairy products to sustain human health and wellbeing. Betaines are food components widely distributed in plants, animals, microorganisms, and dietary sources. Among betaines, δ-valerobetaine (N,N,N-trimethyl-5-aminovaleric acid, δVB) shares a metabolic pathway common to γ-butyrobetaine (γBB). The biological properties of δVB are particularly attractive, as it possesses antioxidant, anti-inflammatory and anticancer activities. Here, we investigated the possible synergism between δVB and the structurally related γBB, to date unexplored, by testing the in vitro anticancer activity in head and neck squamous cell carcinoma cell lines, FaDu, UM-SCC-17A and Cal 27. Among cell lines tested, results indicated that betaines showed the highest effect in reducing Cal 27 cell proliferation up to 72 h (p < 0.01). This effect was enhanced when betaines were administered in combination (δVB plus γBB) (p < 0.001). Inhibition of cell growth by δVB plus γBB involved reactive oxygen species (ROS) accumulation, upregulation of sirtuin 1 (SIRT1), and apoptosis (p < 0.001). SIRT1 gene silencing by small interfering RNA decreased the apoptotic effect of δVB plus γBB by modulating downstream procaspase-3 and cyclin B1 (p < 0.05). These findings might have important implications for novel prevention strategies for tongue squamous cell carcinoma by targeting SIRT1 with naturally occurring betaines. [ABSTRACT FROM AUTHOR]
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- 2020
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136. MiR-148a-3p/SIRT7 Axis Relieves Inflammatory-Induced Endothelial Dysfunction.
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Anastasio, Camilla, Donisi, Isabella, Colloca, Antonino, D'Onofrio, Nunzia, and Balestrieri, Maria Luisa
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ENDOTHELIUM diseases , *CELL death , *GENE expression , *ENDOTHELIAL cells , *HOMEOSTASIS - Abstract
In endothelial cells, miR-148a-3p is involved in several pathological pathways, including chronic inflammatory conditions. However, the molecular mechanism of miR-148a-3p in endothelial inflammatory states is, to date, not fully elucidated. To this end, we investigated the involvement of miR-148a-3p in mitochondrial dysfunction and cell death pathways in human aortic endothelial cells (teloHAECs) treated with interleukin-6 (IL-6), a major driver of vascular dysfunction. The results showed that during IL6-activated inflammatory pathways, including increased protein levels of sirtuin 7 (SIRT7) (p < 0.01), mitochondrial stress (p < 0.001), and apoptosis (p < 0.01), a decreased expression of miR-148a-3p was observed (p < 0.01). The employment of a miR-148a mimic counteracted the IL-6-induced cytokine release (p < 0.01) and apoptotic cell death (p < 0.01), and ameliorated mitochondria redox homeostasis and respiration (p < 0.01). The targeted relationship between miR-148a-3p and SIRT7 was predicted by a bioinformatics database analysis and validated via the dual-luciferase reporter assay. Mechanistically, miR-148a-3p targets the 3′ untranslated regions of SIRT7 mRNA, downregulating its expression (p < 0.01). Herein, these in vitro results support the role of the miR-148a-3p/SIRT7 axis in counteracting mitochondrial damage and apoptosis during endothelial inflammation, unveiling a novel target for future strategies to prevent endothelial dysfunction. [ABSTRACT FROM AUTHOR]
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- 2024
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137. Metabolic Alteration Bridging the Prediabetic State and Colorectal Cancer.
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Colloca, Antonino, Donisi, Isabella, Anastasio, Camilla, Balestrieri, Maria Luisa, and D'Onofrio, Nunzia
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PREDIABETIC state , *COLORECTAL cancer , *THERAPEUTICS , *ADIPOKINES , *DEATH rate , *BRIDGES - Abstract
Prediabetes and colorectal cancer (CRC) represent compelling health burdens responsible for high mortality and morbidity rates, sharing several modifiable risk factors. It has been hypothesized that metabolic abnormalities linking prediabetes and CRC are hyperglycemia, hyperinsulinemia, and adipokines imbalance. The chronic stimulation related to these metabolic signatures can favor CRC onset and development, as well as negatively influence CRC prognosis. To date, the growing burden of prediabetes and CRC has generated a global interest in defining their epidemiological and molecular relationships. Therefore, a deeper knowledge of the metabolic impairment determinants is compelling to identify the pathological mechanisms promoting the onset of prediabetes and CRC. In this scenario, this review aims to provide a comprehensive overview on the metabolic alterations of prediabetes and CRC as well as an overview of recent preventive and therapeutic approaches for both diseases, focusing on the role of the metabolic state as a pivotal contributor to consider for the development of future preventive and therapeutic strategies. [ABSTRACT FROM AUTHOR]
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- 2024
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138. Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients.
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D'Onofrio, Nunzia, Pieretti, Gorizio, Ciccarelli, Feliciano, Gambardella, Antonio, Passariello, Nicola, Rizzo, Maria Rosaria, Barbieri, Michelangela, Marfella, Raffaele, Nicoletti, Gianfranco, Balestrieri, Maria Luisa, and Sardu, Celestino
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ADIPOSE tissues , *INSULIN resistance , *GLUCOSE , *METFORMIN , *NITROTYROSINE - Abstract
The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin (p < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy. [ABSTRACT FROM AUTHOR]
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- 2019
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139. Chemopreventive effect of a milk whey by-product derived from Buffalo (Bubalus bubalis) in protecting from colorectal carcinogenesis.
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Cacciola, Nunzio Antonio, Venneri, Tommaso, Salzano, Angela, D'Onofrio, Nunzia, Martano, Manuela, Saggese, Anella, Vinale, Francesco, Neglia, Gianluca, Campanile, Ciro, Baccigalupi, Loredana, Maiolino, Paola, Cuozzo, Mariarosaria, Russo, Roberto, Balestrieri, Maria Luisa, D'Occhio, Michael John, Ricca, Ezio, Borrelli, Francesca, and Campanile, Giuseppe
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MICE , *WATER buffalo , *POLY(ADP-ribose) polymerase , *MICROBIAL metabolites , *WHEY , *GUT microbiome , *BUTYRIC acid - Abstract
Background: Several studies show that natural foods are a source of compounds with anticancer properties that affect the gut microbiota and its metabolites. In the present study, we investigate the effect of a delactosed buffalo milk whey by-product (DMW) on colorectal carcinogenesis. Methods: The effect of DMW on colorectal carcinoma (CRC) was investigated in the established mouse model of azoxymethane (AOM)-induced colon carcinoma, which closely resembles the human clinical condition of CRC. The effect of DMW on CRC immortalized cell lines was also evaluated to further identify the antineoplastic mechanism of action. Results: Pretreatment of AOM-treated mice with DMW significantly (P < 0.05) reduced the percentage of mice bearing both aberrant crypt foci with more than four crypts (which are early precancerous lesions that progress to CRC) and tumors. In addition, DMW completely counteracted the effect of AOM on protein expression of caspase-9, cleaved caspase-3 and poly ADP-ribose polymerase in colonic tissue. Administration of DMW alone (i.e. without AOM) resulted in changes in the composition of the gut microbiota, leading to enrichment or depletion of genera associated with health and disease, respectively. DMW was also able to restore AOM-induced changes in specific genera of the gut microbiota. Specifically, DMW reduced the genera Atopobiaceae, Ruminococcus 1 and Lachnospiraceae XPB1014 and increased the genera Parabacteroides and Candidatus Saccharimonas, which were increased and reduced, respectively, by AOM. Blood levels of butyric acid and cancer diagnostic markers (5-methylcytidine and glycerophosphocholine), which were increased by AOM treatment, were reduced by DMW. Furthermore, DMW exerted cytotoxic effects on two human CRC cell lines (HCT116 and HT29) and these effects were associated with the induction of apoptotic signaling. Conclusions: Our results suggest that DMW exerts chemopreventive effects and restores the gut microbiota in AOM-induced CRC, and induces cytotoxic effect on CRC cells. DMW could be an important dietary supplement to support a healthy gut microbiota and reduce the prevalence of CRC in humans. ATYCseWUm9Z2DGDMVykgy6 Video Abstract [ABSTRACT FROM AUTHOR]
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- 2023
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140. MiR-148a-3p Promotes Colorectal Cancer Cell Ferroptosis by Targeting SLC7A11.
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Martino, Elisa, Balestrieri, Anna, Aragona, Francesca, Bifulco, Giovanna, Mele, Luigi, Campanile, Giuseppe, Balestrieri, Maria Luisa, and D'Onofrio, Nunzia
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STATISTICS , *ANALYSIS of variance , *APOPTOSIS , *MICRORNA , *COLORECTAL cancer , *CELL survival , *CELLULAR signal transduction , *GENE expression profiling , *DESCRIPTIVE statistics , *CELL lines , *DATA analysis software , *DATA analysis , *CELL surface antigens , *IMMUNODIAGNOSIS - Abstract
Simple Summary: The role of miR-148a-3p in colorectal cancer (CRC) is still debated. In this study, the in vitro antineoplastic effect of miR-148a-3p overexpression in the CRC model is reported. The antitumor activity of miR-148a-3p occurs through apoptosis, mitochondrial impairment, lipid peroxidation, and ferroptosis sustained by the ACSL4/TFRC/Ferritin axis. Bioinformatic analysis and transfection experiments with miR-148a-3p mimics and inhibitors revealed that the cytotoxicity might be related to the downregulation of SLC7A11. These findings, extending knowledge on functional and molecular mechanisms, unveil the oncosuppressor role of miR-148a-3p, pointing out its potential as a diagnostic and therapeutic biomarker in CRC. Ferroptosis, an iron-dependent form of cell death, and dysregulated microRNA (miRNA) expression correlate with colorectal cancer (CRC) development and progression. The tumor suppressor ability of miR-148a-3p has been reported for several cancers. Nevertheless, the role of miR-148a-3p in CRC remains largely undetermined. Here, we aim at investigating the molecular mechanisms and regulatory targets of miR-148a-3p in the CRC cell death mechanism(s). To this end, miR-148a-3p expression was evaluated in SW480 and SW620 cells and normal colon epithelial CCD 841 CoN cells with quantitative real-time polymerase chain reaction (qRT-PCR). Data reported a reduction of miR-148a-3p expression in SW480 and SW620 cells compared to non-tumor cells (p < 0.05). Overexpression of miR-148a selectively inhibited CRC cell viability (p < 0.001), while weakly affecting normal CCD 841 CoN cell survival (p < 0.05). At the cellular level, miR-148a-3p mimics promoted apoptotic cell death via caspase-3 activation (p < 0.001), accumulation of mitochondrial reactive oxygen species (ROS) (p < 0.001), and membrane depolarization (p < 0.001). Moreover, miR-148a-3p overexpression induced lipid peroxidation (p < 0.01), GPX4 downregulation (p < 0.01), and ferroptosis (p < 0.01), as revealed by intracellular and mitochondrial iron accumulation and ACSL4/TFRC/Ferritin modulation. In addition, levels of SLC7A11 mRNA and protein, the cellular targets of miR-148a-3p predicted by bioinformatic tools, were suppressed by miR-148a-3p's overexpression. On the contrary, the downregulation of miR-148a-3p boosted SLC7A11 gene expression and suppressed ferroptosis. Together, these in vitro findings reveal that miR-148a-3p can function as a tumor suppressor in CRC by targeting SLC7A11 and activating ferroptosis, opening new perspectives for the rationale of therapeutic strategies through targeting the miR-148a-3p/SLC7A11 pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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141. SGLT2 breast expression could affect the cardiovascular performance in pre-menopausal women with fatty vs. non fatty breast via over-inflammation and sirtuins' down regulation.
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Sardu, Celestino, Gatta, Gianluca, Pieretti, Gorizio, Onofrio, Nunzia D', Balestrieri, Maria Luisa, Scisciola, Lucia, Cappabianca, Salvatore, Ferraro, Giuseppe, Nicoletti, Giovanni Francesco, Signoriello, Giuseppe, Sportiello, Liberata, Savarese, Gianluigi, Melchionna, Mario, Ciccarelli, Feliciano, La Forgia, Daniele, Paolisso, Giuseppe, and Marfella, Raffaele
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SIRTUINS , *CAROTID intima-media thickness , *ADIPOSE tissues , *GLUCOSE transporters , *INVERSE relationships (Mathematics) - Abstract
• Pre-menopausal women with lowest breast fat-density (fatty breast) vs. higher breast fat-density (non-fatty breast) are high-risk population for cardiovascular diseases and worse prognosis. • The worse cardiovascular prognosis could be due to expression in the breast fat tissue in fatty vs. non-fatty pre-menopausal women of sodium glucose transporter 2 (SGLT2), inflammatory cytokines and sirtuins. • Indeed, these molecular effectors could condition the intima-media wall thickness (IMT), left ventricle mass (LVM), left ventricle ejection fraction (LVEF), and myocardial performance index (MPI), and its normalization. • The fatty vs. non-fatty breast women over-expressed SGLT2/inflammatory cytokines, and down-regulated breast sirtuins. • SGLT2/inflammatory cytokines expression and inversely the tSIRT3 and breast percentage density linked to ΔMPI at 1 year of follow-up. • Fatty breast and SGLT2 inversely predicted the normalization of cardiac performance (NCP). • SIRT-3 increased the probability of NCP at 1 year of follow-up. To evaluate the expression of sodium-glucose transporter 2 (SGLT2), inflammatory cytokines, and sirtuins in breast fat tissue at baseline, and serum cytokines of fatty vs. non-fatty pre-menopausal women at baseline, and at 12 months of follow-up. To correlate SGLT2/cytokines/sirtuins expression to clinical variables, and their changes (Δ) at follow-up, as intima-media wall thickness (IMT), left ventricle mass (LVM), left ventricle ejection fraction (LVEF), and myocardial performance index (MPI), and its normalization. Pre-menopausal women with the lowest breast fat density (fatty breast) vs. higher breast fat density (non-fatty breast) are a high-risk population for cardiovascular diseases and worse prognosis. We analyzed SGLT2/cytokines/sirtuins of excised fatty breasts of fatty vs. non-fatty pre-menopausal women. We correlated SGLT2/cytokines/sirtuins to Δ IMT, Δ LVM, Δ LVEF, and Δ MPI, and normal cardiac performance (NCP) at 1 year of follow-up. fatty vs. non-fatty breast over-expressed SGLT2/inflammatory cytokines, with lowest values of sirtuins (p <0.05). We found a direct correlation between SGLT2 (R2 0.745), TNFα (R2 0.262), and ΔMPI (p <0.05), and an inverse correlation between breast density (R2 -0.198), SIRT-3 (R2–0.181), and ΔMPI (p <0.05). Fatty breast (0.761, CI 95% [0.101–0.915]), SGLT2 (0.812, CI 95% [0.674–0.978]) and SIRT-3 (1.945, CI 95% [1.201–3.148]) predicted NCP at 1 year of follow-up. fatty vs. non-fatty breast women over-expressed SGLT2/inflammatory cytokines, and down-regulated breast sirtuins. SGLT2/inflammatory cytokines expression and inversely the tissue sirtuin 3 (tSIRT3) and breast percentage density linked to ΔMPI at 1 year of follow-up. Fatty breast and SGLT2 inversely predicted NCP; SIRT-3 increased the probability of NCP at 1 year of follow-up. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2023
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142. MicroRNAs modulation and clinical outcomes at 1 year of follow-up in obese patients with pre-diabetes treated with metformin vs. placebo.
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Sardu, Celestino, Trotta, Maria Consiglia, Pieretti, Gorizio, Gatta, Gianluca, Ferraro, Giuseppe, Nicoletti, Giovanni Francesco, D' Onofrio, Nunzia, Balestrieri, Maria Luisa, D' Amico, Michele, Abbatecola, Angela, Ferraraccio, Franca, Panarese, Iacopo, Paolisso, Giuseppe, and Marfella, Raffaele
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TREATMENT effectiveness , *METFORMIN , *PREDIABETIC state , *OBESITY , *MICRORNA , *PLACEBOS - Abstract
Backgrounds: Obese pre-diabetics over express cytokines that influence myocardial function via microRNAs (miRs) expression. Objectives: To evaluate inflammatory/oxidative stress, miRs' expression and cardiovascular function in obese pre-diabetics assigned to metformin therapy vs. placebo vs. normo-glycemics at 12 months of follow-up. Materials and methods: Eighty-three obese patients after abdominoplastic surgery were divided in pre-diabetics (n 55), normo-glycemics (n 28), and assigned to hypocaloric diet. Pre-diabetics were assigned to metformin (n 23) or to placebo (n 22) plus hypocaloric diet. Results: Obese pre-diabetics in metformin vs. placebo, and obese pre-diabetics with placebo vs. normoglycemics, had significant differences about IMT, MPI, and LVM (p < 0.05). Obese pre-diabetics in metformin vs. placebo showed significant reduction in serum miR-195 and miR-27 (p < 0.05). Obese pre-diabetics in metformin vs. normoglycemics showed higher expression of serum miR-195 and miR-27 (p < 0.05). Finally, we found inverse relation between IMT and insulin, HOMA-IR, miR-195, miR-27; between LVEF and Insulin, HOMA-IR, miR-195 and miR-27. We found inverse correlation between LVM and sirtuin-1, Insulin, HOMA-IR, miR-195 and miR-27, and direct correlation with interleukin-6. MPI inversely linked to miR-195 and miR-27. Conclusions: In obese pre-diabetics', metformin significantly reduces inflammation/oxidative stress, and miR-195 and miR-27, with reduction in LVM, IMT. [ABSTRACT FROM AUTHOR]
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- 2021
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143. Green feed increases antioxidant and antineoplastic activity of buffalo milk: A globally significant livestock.
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Salzano, Angela, Neglia, Gianluca, D'Onofrio, Nunzia, Balestrieri, Maria Luisa, Limone, Antonio, Cotticelli, Alessio, Marrone, Raffaele, Anastasio, Aniello, D'Occhio, Michael J., and Campanile, Giuseppe
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ALFALFA as feed , *MILK , *REACTIVE oxygen species , *MILK consumption , *LIVESTOCK , *DAIRY processing , *ALFALFA - Abstract
• Green feed increases concentration of health-promoting molecules in buffalo milk. • Green feed increases the antioxidant activity of buffalo milk. • Green feed increases the antineoplastic of buffalo milk. • Increased biomolecules support buffalo milk consumption within a balanced diet. The effect of green feed on health-promoting biomolecules in milk was examined in dairy buffaloes. Buffaloes received a total mixed ration (TMR) (Control, C; n = 40) or TMR + alfalfa green feed (30% of diet) (Treated, T; n = 40). Biomolecules and functional activity were measured in milk obtained twice-monthly. Treated buffaloes had higher milk l -carnitine, acetyl- l -carnitine, propionyl- l -carnitine and δ-valerobetaine (P < 0.01). They also had higher antioxidant activity (P < 0.01). Compared with C buffaloes, milk of T buffaloes improved the viability of endothelial cells exposed to high-glucose (P < 0.01), and reduced intracellular lipid peroxidation, reactive oxygen species (ROS), and cytokine release (P < 0.01). Milk of T buffaloes inhibited with greater potency the viability of human HCT116 and Cal 27 cancer cells (P < 0.001). The findings show that including green feed in the diet of dairy buffaloes enhances health-promoting biomolecules and the antioxidant and antineoplastic properties of milk. [ABSTRACT FROM AUTHOR]
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- 2021
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144. SIRT3 mediates the effects of PCSK9 inhibitors on inflammation, autophagy, and oxidative stress in endothelial cells
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Nunzia D'Onofrio, Francesco Prattichizzo, Raffaele Marfella, Celestino Sardu, Elisa Martino, Lucia Scisciola, Lorenza Marfella, Rosalba La Grotta, Chiara Frigé, Giuseppe Paolisso, Antonio Ceriello, Maria Luisa Balestrieri, D'Onofrio, Nunzia, Prattichizzo, Francesco, Marfella, Raffaele, Sardu, Celestino, Martino, Elisa, Scisciola, Lucia, Marfella, Lorenza, Grotta, Rosalba La, Frigé, Chiara, Paolisso, Giuseppe, Ceriello, Antonio, and Balestrieri, Maria Luisa
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Medicine (miscellaneous) ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) - Published
- 2023
145. SGLT-2 inhibitors and in-stent restenosis-related events after acute myocardial infarction: an observational study in patients with type 2 diabetes
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Raffaele Marfella, Celestino Sardu, Nunzia D’Onofrio, Carlo Fumagalli, Lucia Scisciola, Ferdinando Carlo Sasso, Mario Siniscalchi, Ludovica Vittoria Marfella, Davide D’Andrea, Fabio Minicucci, Giuseppe Signoriello, Arturo Cesaro, Maria Consiglia Trotta, Chiara Frigé, Francesco Prattichizzo, Maria Luisa Balestrieri, Antonio Ceriello, Paolo Calabrò, Ciro Mauro, Luca del Viscovo, Giuseppe Paolisso, Marfella, Raffaele, Sardu, Celestino, D'Onofrio, Nunzia, Fumagalli, Carlo, Scisciola, Lucia, Sasso, Ferdinando Carlo, Siniscalchi, Mario, Marfella, Ludovica Vittoria, D'Andrea, Davide, Minicucci, Fabio, Signoriello, Giuseppe, Cesaro, Arturo, Trotta, Maria Consiglia, Frigé, Chiara, Prattichizzo, Francesco, Balestrieri, Maria Luisa, Ceriello, Antonio, Calabrò, Paolo, Mauro, Ciro, Del Viscovo, Luca, and Paolisso, Giuseppe
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Glycemic control ,Major adverse cardiovascular event ,SGLT-2 inhibitor ,Restenosi ,Type 2 diabetes ,General Medicine - Abstract
Background No study evaluated the incidence of intra-stent restenosis (ISR)-related events in patients with type 2 diabetes (T2DM) and acute myocardial infarction (AMI) treated or not with sodium/glucose cotransporter 2 inhibitors (SGLT2i). Methods We recruited 377 patients with T2DM and AMI undergoing percutaneous coronary intervention (PCI). Among them, 177 T2DM were treated with SGLT2 inhibitors before PCI. The primary outcome was major adverse cardiovascular events (MACE) defined as cardiac death, re-infarction, and heart failure related to ISR. In patients without ISR, minimal lumen area and minimal lumen diameter were assessed by coronary CT-angiography at 1-year follow-up. Results Glycemic control was similar in SGLT2i-treated patients and never SGLT2i-users. The incidence of ISR-related MACE was higher in never SGLT2i-users compared with SGLT2i-treated patients, an effect independent of glycemic status (HR = 0.418, 95% CI = 0.241–0.725, P = 0.002) and observed also in the subgroup of patients with HbA1c < 7% (HR = 0.393, 95% CI = 0.157–0.984, P = 0.027). In patients without the event, the stent patency was greater in SGLT2i-treated patients compared with never SGLT2i-users at 1-year follow-up. Conclusions SGLT2i treatment in T2DM is associated with a reduced incidence of ISR-related events, independently of glycemic control.
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- 2023
146. SGLT2 breast expression could affect the cardiovascular performance in pre-menopausal women with fatty vs. non fatty breast via over-inflammation and sirtuins' down regulation
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Celestino Sardu, Gianluca Gatta, Gorizio Pieretti, Nunzia D’ Onofrio, Maria Luisa Balestrieri, Lucia Scisciola, Salvatore Cappabianca, Giuseppe Ferraro, Giovanni Francesco Nicoletti, Giuseppe Signoriello, Liberata Sportiello, Gianluigi Savarese, Mario Melchionna, Feliciano Ciccarelli, Daniele La Forgia, Giuseppe Paolisso, Raffaele Marfella, Sardu, Celestino, Gatta, Gianluca, Pieretti, Gorizio, Onofrio, Nunzia D', Balestrieri, Maria Luisa, Scisciola, Lucia, Cappabianca, Salvatore, Ferraro, Giuseppe, Nicoletti, Giovanni Francesco, Signoriello, Giuseppe, Sportiello, Liberata, Savarese, Gianluigi, Melchionna, Mario, Ciccarelli, Feliciano, La Forgia, Daniele, Paolisso, Giuseppe, and Marfella, Raffaele
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Inflammation ,Internal Medicine ,Breast density ,Sirtuins ,Cardiac performance ,SGLT2 - Abstract
Objectives: To evaluate the expression of sodium-glucose transporter 2 (SGLT2), inflammatory cytokines, and sirtuins in breast fat tissue at baseline, and serum cytokines of fatty vs. non-fatty pre-menopausal women at baseline, and at 12 months of follow-up. To correlate SGLT2/cytokines/sirtuins expression to clinical variables, and their changes (Δ) at follow-up, as intima-media wall thickness (IMT), left ventricle mass (LVM), left ventricle ejection fraction (LVEF), and myocardial performance index (MPI), and its normalization. Background: Pre-menopausal women with the lowest breast fat density (fatty breast) vs. higher breast fat density (non-fatty breast) are a high-risk population for cardiovascular diseases and worse prognosis. Methods: We analyzed SGLT2/cytokines/sirtuins of excised fatty breasts of fatty vs. non-fatty pre-menopausal women. We correlated SGLT2/cytokines/sirtuins to Δ IMT, Δ LVM, Δ LVEF, and Δ MPI, and normal cardiac performance (NCP) at 1 year of follow-up. Results: fatty vs. non-fatty breast over-expressed SGLT2/inflammatory cytokines, with lowest values of sirtuins (p
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- 2023
147. Evidence of an anti-inflammatory effect of PCSK9 inhibitors within the human atherosclerotic plaque.
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Marfella, Raffaele, Prattichizzo, Francesco, Sardu, Celestino, Paolisso, Pasquale, D'Onofrio, Nunzia, Scisciola, Lucia, La Grotta, Rosalba, Frigé, Chiara, Ferraraccio, Franca, Panarese, Iacopo, Fanelli, Mara, Modugno, Piero, Calafiore, Antonio Maria, Melchionna, Mario, Sasso, Ferdinando Carlo, Furbatto, Fulvio, D'Andrea, Davide, Siniscalchi, Mario, Mauro, Ciro, and Cesaro, Arturo
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ATHEROSCLEROTIC plaque , *MYOCARDIAL infarction , *CAROTID endarterectomy , *STROKE , *NLRP3 protein , *MIFEPRISTONE - Abstract
Preclinical evidence suggests that proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors hold anti-inflammatory properties independently of their ability to lower LDL-cholesterol (C). However, whether PCSK9 inhibitors exert anti-inflammatory effects within the atherosclerotic plaque in humans is unknown. We explored the impact of PCSK9 inhibitors, used as monotherapy, compared with other lipid-lowering drugs (oLLD) on the expression of inflammatory markers within the plaque, assessing also the subsequent incidence of cardiovascular events. In an observational study, we recruited 645 patients on stable therapy for at least six months and undergoing carotid endarterectomy, categorizing patients according to the use of PCSK9 inhibitors only (n = 159) or oLLD (n = 486). We evaluated the expression of NLRP3, caspase-1, IL-1β, TNFα, NF-kB, PCSK9, SIRT3, CD68, MMP-9, and collagen within the plaques in the two groups through immunohistochemistry, ELISA, or immunoblot. A composite outcome including non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality was assessed during a 678 ± 120 days follow-up after the procedure. Patients treated with PCSK9 inhibitors had a lower expression of pro-inflammatory proteins and a higher abundance of SIRT3 and collagen within the plaque, a result obtained despite comparable levels of circulating hs-CRP and observed also in LDL-C-matched subgroups with LDL-C levels <100 mg/dL. Patients treated with PCSK9 inhibitors showed a decreased risk of developing the outcome compared with patients on oLLD, also after adjustment for multiple variables including LDL-C (adjusted hazard ratio 0.262; 95% CI 0.131–0.524; p < 0.001). The expression of PCSK9 correlated positively with that of pro-inflammatory proteins, which burden was associated with a higher risk of developing the outcome, independently of the therapeutic regimen. The use of PCSK9 inhibitors is accompanied by a beneficial remodelling of the inflammatory burden within the human atheroma, an effect possibly or partly independent of their LDL-C lowering ability. This phenomenon might provide an additional cardiovascular benefit. [Display omitted] • Patients on therapy with PCSK9 inhibitors have a lower burden of inflammatory proteins within the carotid plaque. • Patients treated with PCSK9 inhibitors have a higher expression of SIRT3 within the plaque and a more stable plaque phenotype. • Treatment with a PCSK9 inhibitor monotherapy is associated with a decreased incidence of a composite of myocardial infarction, stroke, and mortality. • The expression of inflammatory proteins within the plaque is associated with the incidence of myocardial infarction, stroke, and mortality. [ABSTRACT FROM AUTHOR]
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- 2023
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148. Angiotensin receptor/Neprilysin inhibitor effects in CRTd non-responders: From epigenetic to clinical beside
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Celestino Sardu, Massimo Massetti, Lucia Scisciola, Maria Consiglia Trotta, Matteo Santamaria, Mario Volpicelli, Valentino Ducceschi, Giuseppe Signoriello, Nunzia D’Onofrio, Ludovica Marfella, Flavia Casolaro, Michele D.’ Amico, Antonio Ruocco, Maria Luisa Balestrieri, Ciro Mauro, Concetta Rafaniello, Annalisa Capuano, Giuseppe Paolisso, Raffaele Marfella, Sardu, Celestino, Massetti, Massimo, Scisciola, Lucia, Trotta, Maria Consiglia, Santamaria, Matteo, Volpicelli, Mario, Ducceschi, Valentino, Signoriello, Giuseppe, D'Onofrio, Nunzia, Marfella, Ludovica, Casolaro, Flavia, Amico, Michele D ', Ruocco, Antonio, Balestrieri, Maria Luisa, Mauro, Ciro, Rafaniello, Concetta, Capuano, Annalisa, Paolisso, Giuseppe, and Marfella, Raffaele
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CRTd non-responder ,Pharmacology ,Heart Failure ,Receptors, Angiotensin ,Ventricular Remodeling ,Clinical outcome ,MiRs regulation ,Stroke Volume ,HFrEF ,Epigenesis, Genetic ,Cardiac Resynchronization Therapy ,Angiotensin Receptor Antagonists ,Drug Combinations ,MicroRNAs ,Treatment Outcome ,Clinical outcomes ,Humans ,Neprilysin ,Settore MED/23 - CHIRURGIA CARDIACA ,CRTd non-responders ,Antihypertensive Agents - Abstract
We evaluated whether Angiotensin receptor/Neprilysin inhibitors (ARNI) reduce heart failure (HF) hospitalizations and deaths in cardiac resynchronization therapy with defibrillator (CRTd) non-responders patients at 12 months of follow-up, modulating microRNAs (miRs) implied in adverse cardiac remodeling.adverse cardiac remodeling characterized by left ventricle ejection fraction (LVEF) reduction, left ventricular end-systolic volume (LVESv) increase, and the 6-minute walking test (6MWT) reduction are relevant pathological mechanisms in CRTd non-responders and could be linked to changes in miRNAs (miRs), regulating cardiac fibrosis, apoptosis, and hypertrophy.miRs levels and clinical outcomes (LVEF, cardiac deaths, and 6MWT) were evaluated at baseline and one year of follow-up in CRTd non-responders divided into ARNI-users and Non-ARNI users.At baseline, there were no differences in levels of inflammatory markers, miR-18, miR-145, and miR-181 (p 0.05) between Non-ARNI users (n 106) and ARNI-users (n 312). At one year of follow-up, ARNI-users vs. Non-ARNI users showed lowest inflammatory markers (p 0.01) and miR-181 levels (p 0.01) and higher values of miR-18 (p 0.01)and miR-145 (p 0.01). At one year of follow-up, ARNI-users had a higher increase of LVEF (p 0.01) and 6MWT (p 0.01) along with a more significant reduction of LVESv (p 0.01) compared to Non-ARNI users. Cox regression analysis evidenced that ARNI-based therapies increase the probability of anti-remodeling effects of CRTd. Based on symptomatic improvements, echocardiographic and functional classification improvements, 37 (34.9%) patients among ARNI-users became responders, while only twenty (6.4%) patients became responders among Non-ARNi-users.ARNI might influence epigenetic mechanisms modulating miRs implicated in the adverse cardiac remodeling responses to CRTd.
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- 2022
149. Glycaemic control is associated with SARS-CoV-2 breakthrough infections in vaccinated patients with type 2 diabetes
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Raffaele Marfella, Celestino Sardu, Nunzia D’Onofrio, Francesco Prattichizzo, Lucia Scisciola, Vincenzo Messina, Rosalba La Grotta, Maria Luisa Balestrieri, Paolo Maggi, Claudio Napoli, Antonio Ceriello, Giuseppe Paolisso, Marfella, Raffaele, Sardu, Celestino, D'Onofrio, Nunzia, Prattichizzo, Francesco, Scisciola, Lucia, Messina, Vincenzo, La Grotta, Rosalba, Balestrieri, Maria Luisa, Maggi, Paolo, Napoli, Claudio, Ceriello, Antonio, and Paolisso, Giuseppe
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Glycated Hemoglobin ,COVID-19 Vaccines ,Glycated Hemoglobin A ,Multidisciplinary ,SARS-CoV-2 ,COVID-19 Vaccine ,COVID-19 ,General Physics and Astronomy ,Glycemic Control ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology ,Diabetes Mellitus, Type 2 ,Humans ,Female ,RNA, Messenger ,BNT162 Vaccine ,Human - Abstract
Patients with type 2 diabetes (T2D) are characterized by blunted immune responses, which are affected by glycaemic control. Whether glycaemic control influences the response to COVID-19 vaccines and the incidence of SARS-CoV-2 breakthrough infections is unknown. Here we show that poor glycaemic control, assessed as mean HbA1c in the post-vaccination period, is associated with lower immune responses and an increased incidence of SARS-CoV-2 breakthrough infections in T2D patients vaccinated with mRNA-BNT162b2. We report data from a prospective observational study enroling healthcare and educator workers with T2D receiving the mRNA-BNT162b2 vaccine in Campania (Italy) and followed for one year (5 visits, follow-up 346 ± 49 days) after one full vaccination cycle. Considering the 494 subjects completing the study, patients with good glycaemic control (HbA1c one-year mean < 7%) show a higher virus-neutralizing antibody capacity and a better CD4 + T/cytokine response, compared with those with poor control (HbA1c one-year mean ≥ 7%). The one-year mean of HbA1c is linearly associated with the incidence of breakthrough infections (Beta = 0.068; 95% confidence interval [CI], 0.032-0.103; p p = 0.008). Among other factors, only smoking (HR = 0.290, CI 0.146-0.576 for non-smokers; p p
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- 2022
150. Incretin drugs effect on epigenetic machinery: New potential therapeutic implications in preventing vascular diabetic complications
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Giuseppe Paolisso, Rosaria Anna Fontanella, Michelangela Barbieri, Maria Luisa Balestrieri, Lucia Scisciola, Vittoria Cataldo, Raffaele Marfella, Maria Rosaria Rizzo, Nunzia D'Onofrio, Scisciola, Lucia, Rizzo, Maria Rosaria, Cataldo, Vittoria, Fontanella, Rosaria Anna, Balestrieri, Maria Luisa, D'Onofrio, Nunzia, Marfella, Raffaele, Paolisso, Giuseppe, and Barbieri, Michelangela
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Blood Glucose ,0301 basic medicine ,medicine.medical_specialty ,Methyltransferase ,SOD2 ,Gene Expression ,Incretin ,Type 2 diabetes ,Carotid Intima-Media Thickness ,Incretins ,Biochemistry ,Glucagon-Like Peptide-1 Receptor ,Body Mass Index ,Cell Line ,Epigenesis, Genetic ,Diabetes Complications ,03 medical and health sciences ,incretin based drug ,0302 clinical medicine ,Internal medicine ,Genetics ,Humans ,Medicine ,Epigenetics ,Molecular Biology ,Superoxide Dismutase ,business.industry ,NF-kappa B ,Endothelial Cells ,Methylation ,DNA Methylation ,Atherosclerosis ,medicine.disease ,Glucose ,030104 developmental biology ,Endocrinology ,Diabetes Mellitus, Type 2 ,Intima-media thickness ,DNA methylation ,atherosclerosis progression ,cardiovascular system ,type 2 diabetes ,business ,030217 neurology & neurosurgery ,Biotechnology - Abstract
The effect of GLP-1R agonists on DNA methylation levels of NF-κB and SOD2 genes in human aortic endothelial cells exposed to high glucose and in diabetic patients treated and not with incretin-based drugs, was evaluated. Methylation levels, mRNA and protein expression of NF-κB and SOD2 genes were measured in human endothelial cells exposed to high glucose for 7days and treated with GLP-1R agonists. Methylation status of NF-κB and SOD2 promoter was also analyzed in 128 diabetics and 116 nondiabetics and correlated with intima media thickness (ITM), an early marker of atherosclerotic process. Cells exposed to high glucose showed lower NF-κB and SOD2 methylation levels, increased NF-κB and reduced SOD2 expression compared to normal glucose cells. Co-treatment with GLP-1 agonists prevented methylation and genes expression changes induced by high glucose. Both high glucose and incretins exposure increased DNA methyltransferases and demethylases levels. In diabetics, incretin treatment resulted a significant predictor of NF-κB DNA methylation, independently of age, sex, body mass index (BMI), glucose and plasma lipid levels. NF-κB DNA methylation inversely correlated with IMT after adjusting for multiple covariates. Our results firstly provide new evidences of an additional mechanism by which incretin drugs could prevent vascular diabetic complications.
- Published
- 2020
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