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7. A Green Bioactive By-Product Almond Skin Functional Extract for Developing Nutraceutical Formulations with Potential Antimetabolic Activity.

Author

Picerno, Patrizia, Crascì, Lucia, Iannece, Patrizia, Esposito, Tiziana, Franceschelli, Silvia, Pecoraro, Michela, Giannone, Virgilio, Panico, Anna Maria, Aquino, Rita Patrizia, and Lauro, Maria Rosaria

Subjects
FOOD industrial waste, ALMOND, FREE radical scavengers, EPICATECHIN, BIOPOLYMERS, EXTRACTS
Abstract

(1) Background: almond peels are rich in polyphenols such as catechin and epicatechin, which are important anti-free-radical agents, anti-inflammatory compounds, and capable of breaking down cholesterol plaques. This work aims to evaluate the biological and technological activity of a "green" dry aqueous extract from Sicilian almond peels, a waste product of the food industry, and to develop healthy nutraceuticals with natural ingredients. Eudraguard® Natural is a natural coating polymer chosen to develop atomized formulations that improve the technological properties of the extract. (2) Methods: the antioxidant and free radical scavenger activity of the extract was rated using different methods (DPPH assay, ABTS, ORAC, NO). The metalloproteinases of the extracts (MMP-2 and MMP-9), the enhanced inhibition of the final glycation products, and the effects of the compounds on cell viability were also tested. All pure materials and formulations were characterized using UV, HPLC, FTIR, DSC, and SEM methods. (3) Results: almond peel extract showed appreciable antioxidant and free radical activity with a stronger NO inhibition effect, strong activity on MMP-2, and good antiglycative effects. In light of this, a food supplement with added health value was formulated. Eudraguard® Natural acted as a swelling substrate by improving extract solubility and dissolution/release (4) Conclusions: almond peel extract has significant antioxidant activity and MMP/AGE inhibition effects, resulting in an optimal candidate to formulate safe microsystems with potential antimetabolic activity. Eudraguard® Natural is capable of obtaining spray-dried microsystems with an improvement in the extract's biological and technological characteristics. It also protects the dry extract from degradation and oxidation, prolonging the shelf life of the final product. [ABSTRACT FROM AUTHOR]

Published
2023
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13. Costimulation of CD40 and type-I interferon immune pathways by a bifunctional molecule in HBV infection models and healthy non-human primates

Author

Marniquet, Xavier, primary, Dajon, Marion, additional, Montegut, Julie, additional, Giusepponi, Maria Elena, additional, Pecoraro, Michela, additional, Vicentini, Elena, additional, Morandini, Francesca, additional, Zanderigo, Floriana, additional, Federico, Denise, additional, Bonnin, Odile, additional, Neveu, Gregory, additional, Blanc, Charlotte, additional, Marcou, Christelle, additional, Lavaux, Juliette, additional, Didier, Michel, additional, Boldina, Galina, additional, Dumas, Jacques, additional, Bouqin, Thomas, additional, Milla, Annabelle, additional, Watson, Hugh, additional, Carter, Kara, additional, and Alam, Antoine, additional

Published
2022
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15. Cytotoxic Sesquiterpenoids from Ammoides atlantica Aerial Parts

Author

Boudermine, Sihem, primary, Parisi, Valentina, additional, Lemoui, Redouane, additional, Boudiar, Tarek, additional, Chini, Maria Giovanna, additional, Franceschelli, Silvia, additional, Pecoraro, Michela, additional, Pascale, Maria, additional, Bifulco, Giuseppe, additional, Braca, Alessandra, additional, De Tommasi, Nunziatina, additional, and De Leo, Marinella, additional

Published
2022
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18. Eudraguard ® Natural and Protect: New "Food Grade" Matrices for the Delivery of an Extract from Sorbus domestica L. Leaves Active on the α-Glucosidase Enzyme.

Author

Lauro, Maria Rosaria, Picerno, Patrizia, Franceschelli, Silvia, Pecoraro, Michela, Aquino, Rita Patrizia, and Pignatello, Rosario

Subjects
SPRAY drying, EXTRACTS, FREE radicals, NATURAL products, ENZYMES, LIFTING & carrying (Human mechanics), DIETARY supplements
Abstract

(1) Background: Eudraguard® Natural (EN) and Protect (EP) are polymers regulated for use in dietary supplements in the European Union and the United States to carry natural products, mask unpleasant smells and tastes, ameliorate product handling, and protect products from moisture, light, and oxidation. Moreover, EN and EP can control the release of encapsulated compounds. The aim of this work was the development, preparation, and control of Eudraguard® spray-drying microparticles to obtain powders with easy handling and a stable dietary supplement containing a polar functional extract (SOE) from Sorbus domestica L. leaves. (2) Methods: SOE was characterized using HPLC, NMR, FTIR, DSC, and SEM methods. Furthermore, the SOE's antioxidant/free radical scavenging activity, α-glucosidase inhibition, MTT assay effect on viability in normal cells, and shelf life were evaluated in both the extract and final formulations. (3) Results: The data suggested that SOE, rich in flavonoids, is a bioactive and safe extract; however, from a technological point of view, it was sticky, difficult to handle, and had low aqueous solubility. Despite the fact that EN and EP may undergo changes with spray-drying, they effectively produced easy-to-handle micro-powders with a controlled release profile. Although EN had a weaker capability to coat SOE than EP, EN acted as a substrate that was able to swell, drawing in water and improving the extract solubility and dissolution/release; however, EP was also able to carry the extract and provide SOE with controlled release. (4) Conclusion: Both Eudraguard® products were capable of carrying SOE and improving its antioxidant and α-glucosidase inhibition activities, as well as the extract stability and handling. [ABSTRACT FROM AUTHOR]

Published
2023
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27. Cytotoxic Sesquiterpenoids from Aerial Parts.

Author

Boudermine, Sihem, Parisi, Valentina, Lemoui, Redouane, Boudiar, Tarek, Chini, Maria Giovanna, Franceschelli, Silvia, Pecoraro, Michela, Pascale, Maria, Bifulco, Giuseppe, Braca, Alessandra, De Tommasi, Nunziatina, and De Leo, Marinella

Published
2022
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28. SAT436 - Costimulation of CD40 and type-I interferon immune pathways by a bifunctional molecule in HBV infection models and healthy non-human primates

Author

Marniquet, Xavier, Dajon, Marion, Montegut, Julie, Giusepponi, Maria Elena, Pecoraro, Michela, Vicentini, Elena, Morandini, Francesca, Zanderigo, Floriana, Federico, Denise, Bonnin, Odile, Neveu, Gregory, Blanc, Charlotte, Marcou, Christelle, Lavaux, Juliette, Didier, Michel, Boldina, Galina, Dumas, Jacques, Bouqin, Thomas, Milla, Annabelle, Watson, Hugh, Carter, Kara, and Alam, Antoine

Published
2022
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29. DOXORUBICIN REMEDY OR HARM? CARDIOTOXICITY AND NOT ONLY

Author

Pala, Barbara, Pecoraro, Michela, Di Marcantonio Maria Carmela, Centurione, Lucia, Budani, Mc, Tiboni, Gm, Muraro, Raffaella, Pinto, Aldo, Popolo, Ada, and Mincione, Gabriella.

Subjects
Doxorubicin Cardiotoxicity Reactive Oxigen Species
Published
2019

31. Molecular basis of cardiomiopathy

Author

Pecoraro, Michela, Sbardella, Gianluca, Popolo, Ada, and Pinto, Aldo

Subjects
Connexin 43, BIO/14 FARMACOLOGIA, cardiovascular system, sense organs, biological phenomena, cell phenomena, and immunity, Hypoxia, Cardiotoxicity
Abstract

2016 - 2017, The normal heart rhythm is guaranteed by an important intercellular junctions system, named Gap Junction (GJs). Each GJs consists of two units called connexons formed by six specific trans-membrane proteins named connexins (Cx). Recent reports suggest the presence of Cx43 in the inner mitochondrial membrane where it plays an important cardioprotection mechanism. Alterations in Cx43 expression and distribution were observed in several myocardium disease; i.e. in hypertrophic cardiomyopathy, heart failure and ischemia. Thus, in this doctoral study, we investigated the role of Cx43, and in particular of mitochondrial Cx43, in different cardiomyopaties models... [edited by Author], XXX ciclo

Published
2018

32. Halimium halimifolium: From the Chemical and Functional Characterization to a Nutraceutical Ingredient Design

Author

Kerbab, Khawla, additional, Sansone, Francesca, additional, Zaiter, Lahcene, additional, Esposito, Tiziana, additional, Celano, Rita, additional, Franceschelli, Silvia, additional, Pecoraro, Michela, additional, Benayache, Fadila, additional, Rastrelli, Luca, additional, Picerno, Patrizia, additional, Aquino, Rita P., additional, and Mencherini, Teresa, additional

Published
2019
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34. Cytotoxic Sesquiterpenoids from Ammoides atlanticaAerial Parts

Author

Boudermine, Sihem, Parisi, Valentina, Lemoui, Redouane, Boudiar, Tarek, Chini, Maria Giovanna, Franceschelli, Silvia, Pecoraro, Michela, Pascale, Maria, Bifulco, Giuseppe, Braca, Alessandra, De Tommasi, Nunziatina, and De Leo, Marinella

Abstract

Seven new terpenoids, namely, guaiane (1–4), eudesmane (5), and bisabolane (6) sesquiterpenoids and a furanone (7), were isolated from the aerial parts of Ammoides atlantica, a herbaceous plant growing in Algeria, together with eight known compounds. All metabolites were characterized by their 1D and 2D NMR and HRESIMS data. A combined DFT/NMR method was applied to study the relative configurations of 1–4, 6, and 7. All compounds, except 2, were assayed against MCF-7, A375, A549, HaCaT, and Jurkat cell lines. Compounds 8, 10, and 11induced a dose-dependent reduction in cell viability with different potency on almost all cell lines used. The most active compounds, 8and 10, were studied to assess their potential apoptotic effects and cell cycle inhibition.

Published
2022
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37. Cardiotoxic effects of short-term doxorubicin administration: Involvement of connexin 43 in calcium impairment

Author

Pecoraro, Michela, Rodríguez-Sinovas, Antonio, Marzocco, Stefania, Ciccarelli, Michele, Iaccarino, Guido, Pinto, Aldo, Popolo, Ada, Universitat Autònoma de Barcelona, Pecoraro, M., Rodriguez-Sinovas, A., Marzocco, S., Ciccarelli, M., Iaccarino, G., Pinto, A., and Popolo, A.

Subjects
0301 basic medicine, Time Factors, connexin 43, doxorubicin, cardiotoxicity, calcium homeostasis, mitochondria, Connexin, Sarcoplasmic Reticulum Calcium-Transporting ATPase, Pharmacology, lcsh:Chemistry, Mice, Calcium homeostasis, Myocytes, Cardiac, lcsh:QH301-705.5, Spectroscopy, Calcium-Binding Protein, Antibiotics, Antineoplastic, medicine.diagnostic_test, Computer Science Applications1707 Computer Vision and Pattern Recognition, General Medicine, Calcium homeostasi, Computer Science Applications, Phospholamban, Mitochondria, cardiovascular system, Female, Cardiotoxicity, Connexin 43, Doxorubicin, Catalysis, Molecular Biology, Physical and Theoretical Chemistry, Organic Chemistry, Inorganic Chemistry, Cardiomyopathies, medicine.drug, medicine.medical_specialty, Primary Cell Culture, chemistry.chemical_element, Biology, Calcium, Article, Sarcoplasmic Reticulum Calcium-Transporting ATPases, 03 medical and health sciences, Western blot, Internal medicine, medicine, Animals, Cardiomyopathie, Calcium metabolism, Animal, Calcium-Binding Proteins, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Endocrinology, lcsh:Biology (General), lcsh:QD1-999, chemistry, Homeostasis
Abstract

The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial, although alterations in calcium homeostasis, seem to be involved. Since even the Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we have analyzed the effects of DOXO on Cx43 expression and localization. Damage caused by anthracyclines on cardiomyocytes is immediate after each injection, in the present study we used a short-term model of DOXO-induced cardiomyopathy. C57BL/6j female mice were randomly divided in groups and injected with DOXO (2 or 10 mg/kg i.p.) for 1-3 or 7 days once every other day. Cardiac function was assessed by Echocardiography. Sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCAII) and phospholamban (PLB) expression were assessed by Western blot analysis, intracellular [Ca 2+ ] were detected spectrofluorometrically by means of Fura-2 pentakis (acetoxymethyl) ester (FURA-2AM), and Cx43 and pCx43 expression and localization was analyzed by Western blot and confirmed by immunofluorescence analysis. DOXO induces impairment in Ca 2+ homeostasis, already evident after a single administration, and affects Cx43 expression and localization. Our data suggest that DOXO-induced alterations in Ca 2+ homeostasis causes in the cells the induction of compensatory mechanisms until a certain threshold, above which cardiac injury is triggered

Published
2017

38. Chronic Obstructive Pulmonary Disease-Derived Circulating Cells Release IL-18 and IL-33 under Ultrafine Particulate Matter Exposure in a Caspase-1/8-Independent Manner

Author

De Falco, Gianluigi, primary, Colarusso, Chiara, additional, Terlizzi, Michela, additional, Popolo, Ada, additional, Pecoraro, Michela, additional, Commodo, Mario, additional, Minutolo, Patrizia, additional, Sirignano, Mariano, additional, D’Anna, Andrea, additional, Aquino, Rita P., additional, Pinto, Aldo, additional, Molino, Antonio, additional, and Sorrentino, Rosalinda, additional

Published
2017
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40. Anti-Inflammatory, Antioxidant and Crystallographic Studies of N-Palmitoyl-ethanol Amine (PEA) Derivatives

Author

Saturnino, Carmela, primary, Popolo, Ada, additional, Ramunno, Anna, additional, Adesso, Simona, additional, Pecoraro, Michela, additional, Plutino, Maria, additional, Rizzato, Silvia, additional, Albinati, Alberto, additional, Marzocco, Stefania, additional, Sala, Marina, additional, Iacopetta, Domenico, additional, and Sinicropi, Maria, additional

Published
2017
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41. Role of connexin 43 in cardiovascular diseases

Author

Pinto Aldo, Popolo Ada, Pecoraro Michela, and Verrilli Velia

Subjects
Pharmacology, medicine.medical_specialty, Cardiovascular disease, Connexin 43, Ischemia, Hypertrophic cardiomyopathy, Gap junction, Connexin, Mitochondrion, Biology, medicine.disease, Cell biology, Cardiovascular Diseases, Internal medicine, Heart failure, cardiovascular system, Cardiology, medicine, Ischemic preconditioning, Animals, Humans, Inner mitochondrial membrane
Abstract

Gap junctions (GJs) channels provide the basis for intercellular communication in the cardiovascular system for maintenance of the normal cardiac rhythm, regulation of vascular tone and endothelial function as well as metabolic interchange between the cells. They allow the transfer of small molecules and may enable slow calcium wave spreading, transfer of "death" or of "survival" signals. In the cardiomyocytes the most abundant isoform is Connexin 43 (Cx43). Alterations in Cx43 expression and distribution were observed in myocardium disease; i.e. in hypertrophic cardiomyopathy, heart failure and ischemia. Recent reports suggest the presence of Cx43 in the mitochondria as well, at least in the inner mitochondrial membrane, where it plays a central role in ischemic preconditioning. In this review, the current knowledge on the relationship between the remodeling of cardiac gap junctions and cardiac diseases are summarized.

Published
2015

43. Remote ischemic conditioning provides humoural cross-species cardioprotection through glycine receptor activation.

Author

Alburquerque-Béjar, Juan José, Barba, Ignasi, Valls-Lacalle, Laura, Ruiz-Meana, Marisol, Pecoraro, Michela, Rodríguez-Sinovas, Antonio, and García-Dorado, David

Subjects
CORONARY disease, GLYCINE receptors, BLOOD plasma, DISCRIMINANT analysis, HEART metabolism
Abstract

Aims: Remote ischaemic conditioning (RIC) releases a humoural factor able to exert cross-species cardioprotection when plasma dialysate is applied to isolated hearts. However, the exact chemical nature of this factor is currently unknown. Methods and results: RIC (4 x 5min femoral occlusion/5min reperfusion) was applied to 10 male pigs, and blood was taken before and after the manoeuvre. Discriminant analysis of ¹H-NMR spectra (n = 10-12) obtained from plasma dialysates (12-14 kDa cut-off) allowed to demonstrate a different metabolic profile between control and postRIC samples, with lactate (2.671 ± 0.294 vs. 3.666 ± 0.291 lmol/mL, P = 0.020), succinate (0.062 ± 0.005 vs. 0.082 ± 0.008 lmol/mL, P = 0.035) and glycine (0.055 ± 0.009 vs. 0.471 ± 0.151 lmol/mL, P = 0.015) being the main responsible for such differences. Plasma dialysates were then given to isolated mice hearts submitted to global ischaemia (35 min) and reperfusion (60 min), for 30 min before ischaemia or during the first 15 min of reflow. Infarct size was significantly reduced when postRIC dialysate was applied before ischaemia as compared with hearts pretreated with control dialysate (44.81 ± 3.22 vs. 55.55 ± 2.53%, P = 0.012, n = 12). Blockade of glycine receptors with strychnine 10 lM inhibited the protective effect caused by pretreatment with postRIC dialysate (52.76 ± 6.94 vs. 51.92 ± 5.78%, P-NS, n = 5), whereas pretreatment with glycine 3 mmol/L, but not succinate 100 lmol/L, mimicked RIC protection (41.90 ± 4.50% in glycine-treated vs. 61.51 ± 5.16 and 64.73 ± 4.47% in succinate-treated and control hearts, respectively, P < 0.05, n = 4-7). Conclusions: RIC releases glycine and exerts cross-species cardioprotection against infarction through glycine receptor activation. [ABSTRACT FROM AUTHOR]

Published
2017
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44. 1,2,4-Triazol-3-yl-thiopropyl-tetrahydrobenzazepines: A Series of Potent and Selective Dopamine D3 Receptor Antagonists

Author

Micheli, Fabrizio, primary, Bonanomi, Giorgio, additional, Blaney, Frank E., additional, Braggio, Simone, additional, Capelli, Anna Maria, additional, Checchia, Anna, additional, Curcuruto, Ornella, additional, Damiani, Federica, additional, Di Fabio, Romano, additional, Donati, Daniele, additional, Gentile, Gabriella, additional, Gribble, Andy, additional, Hamprecht, Dieter, additional, Tedesco, Giovanna, additional, Terreni, Silvia, additional, Tarsi, Luca, additional, Lightfoot, Andrew, additional, Stemp, Geoff, additional, MacDonald, Gregor, additional, Smith, Alex, additional, Pecoraro, Michela, additional, Petrone, Marcella, additional, Perini, Ornella, additional, Piner, Jacqui, additional, Rossi, Tino, additional, Worby, Angela, additional, Pilla, Maria, additional, Valerio, Enzo, additional, Griffante, Cristiana, additional, Mugnaini, Manolo, additional, Wood, Martyn, additional, Scott, Claire, additional, Andreoli, Michela, additional, Lacroix, Laurent, additional, Schwarz, Adam, additional, Gozzi, Alessandro, additional, Bifone, Angelo, additional, Ashby,, Charles R., additional, Hagan, Jim J., additional, and Heidbreder, Christian, additional

Published
2007
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45. Differential Effects of Ebselen on Neutrophil Recruitment, Chemokine, and Inflammatory Mediator Expression in a Rat Model of Lipopolysaccharide-Induced Pulmonary Inflammation

Author

Haddad, El-Bdaoui, primary, McCluskie, Kerryn, additional, Birrell, Mark A., additional, Dabrowski, Dominika, additional, Pecoraro, Michela, additional, Underwood, Steve, additional, Chen, Bei, additional, De Sanctis, George T., additional, Webber, Steve E., additional, Foster, Martyn L., additional, and Belvisi, Maria G., additional

Published
2002
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46. Diazoxide Needs Mitochondrial Connexin43 to Exert Its Cytoprotective Effect in a Cellular Model of CoCl 2 -Induced Hypoxia.

Author

Pecoraro, Michela, Marzocco, Stefania, and Popolo, Ada

Subjects
*CONNEXIN 43, *CYTOPROTECTION, *MITOCHONDRIA, *CAUSES of death, *HYPOXEMIA, *INTRACELLULAR calcium
Abstract

Hypoxia is the leading cause of death in cardiomyocytes. Cells respond to oxygen deprivation by activating cytoprotective programs, such as mitochondrial connexin43 (mCx43) overexpression and the opening of mitochondrial KATP channels, aimed to reduce mitochondrial dysfunction. In this study we used an in vitro model of CoCl2-induced hypoxia to demonstrate that mCx43 and KATP channels cooperate to induce cytoprotection. CoCl2 administration induces apoptosis in H9c2 cells by increasing mitochondrial ROS production, intracellular and mitochondrial calcium overload and by inducing mitochondrial membrane depolarization. Diazoxide, an opener of KATP channels, reduces all these deleterious effects of CoCl2 only in the presence of mCx43. In fact, our results demonstrate that in the presence of radicicol, an inhibitor of Cx43 translocation to mitochondria, the cytoprotective effects of diazoxide disappear. In conclusion, these data confirm that there exists a close functional link between mCx43 and KATP channels. [ABSTRACT FROM AUTHOR]

Published
2021
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47. Chronic Obstructive Pulmonary Disease-Derived Circulating Cells Release IL-18 and IL-33 under Ultrafine Particulate Matter Exposure in a Caspase-1/8-Independent Manner

Author

Gianluigi De Falco, Chiara Colarusso, Michela Terlizzi, Ada Popolo, Michela Pecoraro, Mario Commodo, Patrizia Minutolo, Mariano Sirignano, Andrea D’Anna, Rita P. Aquino, Aldo Pinto, Antonio Molino, Rosalinda Sorrentino, Falco, Gianluigi De, Colarusso, Chiara, Terlizzi, Michela, Popolo, Ada, Pecoraro, Michela, Commodo, Mario, Minutolo, Patrizia, Sirignano, Mariano, D'Anna, Andrea, Aquino, RITA PATRIZIA, Pinto, Aldo, Molino, Antonio, and Sorrentino, Rosalinda

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, Immunology, Caspase 1, combustion-generated ultrafine particles, Peripheral blood mononuclear cell, chronic obstructive pulmonary disease, 03 medical and health sciences, Ultrafine particle, medicine, Immunology and Allergy, Respiratory system, Airway disease, Chronic obstructive pulmonary disease, Combustion-generated ultrafine particles, Inflammation, Peripheral blood mononuclear cells, Original Research, chemistry.chemical_classification, Reactive oxygen species, COPD, Inhalation, Inflammasome, medicine.disease, peripheral blood mononuclear cells, 030104 developmental biology, chemistry, inflammation, Combustion-generated ultrafine particle, lcsh:RC581-607, medicine.drug, airway disease
Abstract

Chronic obstructive pulmonary disease (COPD) is considered the fourth-leading causes of death worldwide; COPD is caused by inhalation of noxious indoor and outdoor particles, especially cigarette smoke that represents the first risk factor for this respiratory disorder. To mimic the effects of particulate matter on COPD, we isolated peripheral blood mononuclear cells (PBMCs) and treated them with combustion-generated ultrafine particles (UFPs) obtained from two different fuel mixtures, namely, pure ethylene and a mixture of ethylene and dimethylfuran (the latter mimicking the combustion of biofuels). UFPs were separated in two fractions: (1) sub-10 nm particles, named nano organic carbon (NOC) particles and (2) primarily soot particles of 20-40 nm and their agglomerates (200 nm). We found that both NOC and soot UFPs induced the release of IL-18 and IL-33 from unstable/exacerbated COPD-derived PBMCs. This effect was associated with higher levels of mitochondrial dysfunction and derived reactive oxygen species, which were higher in PBMCs from unstable COPD patients after combustion-generated UFP exposure. Moreover, lower mRNA expression of the repairing enzyme OGG1 was associated with the higher levels of 8-OH-dG compared with non-smoker and smokers. It was interesting that IL-18 and IL-33 release from PBMCs of unstable COPD patients was not NOD-like receptor 3/caspase-1 or caspase-8-dependent, but rather correlated to caspase-4 release. This effect was not evident in stable COPD-derived PBMCs. Our data suggest that combustion-generated UFPs induce the release of caspase-4-dependent inflammasome from PBMCs of COPD patients compared with healthy subjects, shedding new light into the biology of this key complex in COPD.

Published
2017
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