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Prof. Dr. Matteo A. Russo
IRCCS San Raffaele Pisana and MEBIC Consortium, San Raffaele Rome Open University, 00166 Rome, Italy

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Research Keywords & Expertise

0 Heart Failure
0 Myocarditis
0 molecular cardiology
0 Molecular aspects of Hypoxia and Inflammation in human pathology including cancer
0 Storage diseases (Fabry's disease)

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Hypoxia and inflammation in obesity
Heart Failure

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Journal article
Published: 26 August 2021 in Endocrine, Metabolic & Immune Disorders - Drug Targets
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Despite the evidence that plants do not possess sessile cells, they are able to mount a vigorous immune response against invaders or under stressful conditions. Plants are endowed with pattern recognition receptors (PPRs) which perceive damage-associated molecular patterns and microbe- associated molecular patterns or pathogen-associated molecular patterns (PAMPs), respectively. PPR activation leads to either the initiation of PAMP-triggered immunity (PTI) (early response) or the effector-triggered immunity (ETI). Both PTI and ETI contribute to plant systemic acquired resistance as an expression of immunological memory or trained immunity. PTI is initiated by activation of both receptor-like kinases and receptor-like proteins, while ETI depends on nucleotide- binding leucine-rich-repeat protein receptors for microbe recognition. Plant chloroplasts contribute to both PTI and ETI through the production of peptides, which act as hormones or phytocytokines. Salicylic acid, jasmonic acid and ethylene are the major compounds involved in plant defense. The interaction between plant receptors and/or their products and bacterial components will be discussed. Also, emphasis will be placed on plant microbiome for its contribution to plant immune response. Finally, the mutual interplay between insects and plants will also be illustrated. A better knowledge of plant immunity may pave the way for the exploitation of plant derivatives in the field of agriculture and medicine, as well.

ACS Style

Thea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. Taking Advantage of Plant Defense Mechanisms to Promote Human Health. The Plant Immune System. First of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets 2021, 21, 1183 -1195.

AMA Style

Thea Magrone, Manrico Magrone, Matteo A. Russo, Emilio Jirillo. Taking Advantage of Plant Defense Mechanisms to Promote Human Health. The Plant Immune System. First of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2021; 21 (7):1183-1195.

Chicago/Turabian Style

Thea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. 2021. "Taking Advantage of Plant Defense Mechanisms to Promote Human Health. The Plant Immune System. First of Two Parts." Endocrine, Metabolic & Immune Disorders - Drug Targets 21, no. 7: 1183-1195.

Journal article
Published: 26 August 2021 in Endocrine, Metabolic & Immune Disorders - Drug Targets
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Platelets are cellular fragments derived from bone-marrow megacaryocytes and they are mostly involved in the haemostasis and coagulation. However, according to recent data, platelets are able to perform novel immune functions. In fact, they possess a receptorial armamentarium on their membrane for interacting with innate and adaptive immune cells. In addition, platelets also secrete granules which contain cytokines and chemokines for activating and recruiting even distant immune cells. The participation of platelets in inflammatory processes will also be discussed in view of their dual role in terms of triggering or resolving inflammation. Involvement of platelets in disease will be illustrated, pointing to their versatile function to either up- or down-regulate pathological mechanisms. Finally, despite the availability of some anti-platelet agents, such as aspirin, dietary manipulation of platelet function is currently investigated. In this regard, special emphasis will be placed on dietary omega-3 polyunsaturated fatty acids (PUFAs) and polyphenol effects on platelets. Platelets play a dual role in inflammatory-immune-mediated diseases either activating or deactivating immune cells. Diet based on substances, such as omega-3 PUFAs and polyphenols, may act as a modulator of platelet function, even if more clinical trials are needed to corroborate such a contention.

ACS Style

Thea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. Platelets: Angels and Demons Dancing on the Immune Stage. Nutrition Conducts the Orchestra. Endocrine, Metabolic & Immune Disorders - Drug Targets 2021, 21, 1196 -1218.

AMA Style

Thea Magrone, Manrico Magrone, Matteo A. Russo, Emilio Jirillo. Platelets: Angels and Demons Dancing on the Immune Stage. Nutrition Conducts the Orchestra. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2021; 21 (7):1196-1218.

Chicago/Turabian Style

Thea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. 2021. "Platelets: Angels and Demons Dancing on the Immune Stage. Nutrition Conducts the Orchestra." Endocrine, Metabolic & Immune Disorders - Drug Targets 21, no. 7: 1196-1218.

Journal article
Published: 07 May 2021 in Cells
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Brown adipose tissue (BAT) activity plays a key role in regulating systemic energy. The activation of BAT results in increased energy expenditure, making this tissue an attractive pharmacological target for therapies against obesity and type 2 diabetes. Sirtuin 5 (SIRT5) affects BAT function by regulating adipogenic transcription factor expression and mitochondrial respiration. We analyzed the expression of SIRT5 in the different adipose depots of mice. We treated 3T3-L1 preadipocytes and mouse primary preadipocyte cultures with the SIRT5 inhibitor MC3482 and investigated the effects of this compound on adipose differentiation and function. The administration of MC3482 during the early stages of differentiation promoted the expression of brown adipocyte and mitochondrial biogenesis markers. Upon treatment with MC3482, 3T3-L1 adipocytes showed an increased activation of the AMP-activated protein kinase (AMPK), which is known to stimulate brown adipocyte differentiation. This effect was paralleled by an increase in autophagic/mitophagic flux and a reduction in lipid droplet size, mediated by a higher lipolytic rate. Of note, MC3482 increased the expression and the activity of adipose triglyceride lipase, without modulating hormone-sensitive lipase. Our findings reveal that SIRT5 inhibition stimulates brown adipogenesis in vitro, supporting this approach as a strategy to stimulate BAT and counteract obesity.

ACS Style

Francesca Molinari; Alessandra Feraco; Simone Mirabilii; Serena Saladini; Luigi Sansone; Enza Vernucci; Giada Tomaselli; Vincenzo Marzolla; Dante Rotili; Matteo Russo; Maria Ricciardi; Agostino Tafuri; Antonello Mai; Massimiliano Caprio; Marco Tafani; Andrea Armani. SIRT5 Inhibition Induces Brown Fat-Like Phenotype in 3T3-L1 Preadipocytes. Cells 2021, 10, 1126 .

AMA Style

Francesca Molinari, Alessandra Feraco, Simone Mirabilii, Serena Saladini, Luigi Sansone, Enza Vernucci, Giada Tomaselli, Vincenzo Marzolla, Dante Rotili, Matteo Russo, Maria Ricciardi, Agostino Tafuri, Antonello Mai, Massimiliano Caprio, Marco Tafani, Andrea Armani. SIRT5 Inhibition Induces Brown Fat-Like Phenotype in 3T3-L1 Preadipocytes. Cells. 2021; 10 (5):1126.

Chicago/Turabian Style

Francesca Molinari; Alessandra Feraco; Simone Mirabilii; Serena Saladini; Luigi Sansone; Enza Vernucci; Giada Tomaselli; Vincenzo Marzolla; Dante Rotili; Matteo Russo; Maria Ricciardi; Agostino Tafuri; Antonello Mai; Massimiliano Caprio; Marco Tafani; Andrea Armani. 2021. "SIRT5 Inhibition Induces Brown Fat-Like Phenotype in 3T3-L1 Preadipocytes." Cells 10, no. 5: 1126.

Journal article
Published: 07 May 2021 in International Journal of Molecular Sciences
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Recent findings suggest that epithelial to mesenchymal transition (EMT), a key step during heart development, is involved in cardiac tissue repair following myocardial infarction (MI). MicroRNAs (miRNAs) act as key regulators in EMT processes; however, the mechanisms by which miRNAs target epicardial EMT remain largely unknown. Here, by using an in vitro model of epicardial EMT, we investigated the role of miRNAs as regulators of this process and their potential targets. EMT was induced in murine epicardial-mesothelial cells (EMCs) through TGF β1 treatment for 48, 72, and 96 h as indicated by the expression of EMT-related genes by qRT-PCR, WB, and immunofluorescence. Further, enhanced expression of stemness genes was also detected. Among several EMT-related miRNAs, miR-200c-3p expression resulted as the most strongly suppressed. Interestingly, we also found a significant upregulation of Follistatin-related protein 1 (FSTL1), a miR-200c predicted target already identified as a potent cardiogenic factor produced by epicardial cells that promotes regeneration following MI. Dual-luciferase reporter assay demonstrated that miR-200c-3p directly targeted the 3′-untranslated region of FSTL1 in EMCs. Consistently, WB analysis showed that knockdown of miR-200c-3p significantly increased FSTL1 expression, whereas overexpression of miR-200c-3p counteracted TGF β1-mediated FSTL1 upregulation. Importantly, FSTL1 silencing maintained epithelial features in EMCs, despite EMT induction by TGF β1, and attenuated EMT-associated traits, including migration and stemness. In conclusion, epicardial FSTL1, an important cardiogenic factor in its secreted form, induces EMT, stemness, and migration of EMCs in a miR-200c-3p dependent pathway.

ACS Style

Elena Pontemezzo; Eleonora Foglio; Enza Vernucci; Alessandra Magenta; Marco D’Agostino; Sara Sileno; Elena Astanina; Federico Bussolino; Laura Pellegrini; Antonia Germani; Matteo Russo; Federica Limana. miR-200c-3p Regulates Epitelial-to-Mesenchymal Transition in Epicardial Mesothelial Cells by Targeting Epicardial Follistatin-Related Protein 1. International Journal of Molecular Sciences 2021, 22, 4971 .

AMA Style

Elena Pontemezzo, Eleonora Foglio, Enza Vernucci, Alessandra Magenta, Marco D’Agostino, Sara Sileno, Elena Astanina, Federico Bussolino, Laura Pellegrini, Antonia Germani, Matteo Russo, Federica Limana. miR-200c-3p Regulates Epitelial-to-Mesenchymal Transition in Epicardial Mesothelial Cells by Targeting Epicardial Follistatin-Related Protein 1. International Journal of Molecular Sciences. 2021; 22 (9):4971.

Chicago/Turabian Style

Elena Pontemezzo; Eleonora Foglio; Enza Vernucci; Alessandra Magenta; Marco D’Agostino; Sara Sileno; Elena Astanina; Federico Bussolino; Laura Pellegrini; Antonia Germani; Matteo Russo; Federica Limana. 2021. "miR-200c-3p Regulates Epitelial-to-Mesenchymal Transition in Epicardial Mesothelial Cells by Targeting Epicardial Follistatin-Related Protein 1." International Journal of Molecular Sciences 22, no. 9: 4971.

Journal article
Published: 12 February 2021 in Endocrine, Metabolic & Immune Disorders - Drug Targets
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Background: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce the release of proinflammatory cytokines and nitric oxide (NO), while increasing the levels of interleukin (IL)-10, an anti-inflammatory cytokine. Objective: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients. Methods: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). The other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups, seven dropouts were recorded. Result: At T1 in comparison to T0, in treated patients, values of interferon-γ, IL-4, IL-17, pentraxin 3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo- treated patients, no modifications of biomarkers were evaluated at T1. Conclusion: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols.

ACS Style

Thea Magrone; Emilio Jirillo; Manrico Magrone; Matteo A. Russo; Paolo Romita; Francesco Massari; Caterina Foti. Red Grape Polyphenol Oral Administration Improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis. Endocrine, Metabolic & Immune Disorders - Drug Targets 2021, 21, 374 -384.

AMA Style

Thea Magrone, Emilio Jirillo, Manrico Magrone, Matteo A. Russo, Paolo Romita, Francesco Massari, Caterina Foti. Red Grape Polyphenol Oral Administration Improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2021; 21 (2):374-384.

Chicago/Turabian Style

Thea Magrone; Emilio Jirillo; Manrico Magrone; Matteo A. Russo; Paolo Romita; Francesco Massari; Caterina Foti. 2021. "Red Grape Polyphenol Oral Administration Improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis." Endocrine, Metabolic & Immune Disorders - Drug Targets 21, no. 2: 374-384.

Journal article
Published: 29 December 2020 in Endocrine, Metabolic & Immune Disorders - Drug Targets
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Background: Plants have represented an essential source of foods for human beings, as confirmed by archeological studies that have revealed on old pottery the presence of proteins from cereal and legumes. Specific aims: In this review, major healthy effects derived from the consumption of plant fibers, polyunsaturated fatty acids (PUFAs) and polyphenols, respectively, will be described with special emphasis on their mechanisms of action, both at cellular and molecular levels. Dietary compounds: Fibers exhibit a prevalent prebiotic effect, acting on the intestinal microbiota with the production of protective metabolites, such as short chain fatty acids. Plant PUFAs include α-linolenic and stearidonic acids, which are precursors of other two major PUFAs, namely, eicosapentaenoic and docosahexaenoic acids. Some clinical trials demonstrated the ability of PUFAs to lower the risk of coronary disease, while other trials did not confirm such a finding. Polyphenols are endowed with anti-oxidant and anti-inflammatory activity in view of their property to inhibit NF-κB activation, to induce the anti-inflammatory T regulatory cells and to normalize the intestinal microbiota. The beneficial effects of polyphenols on obesity/diabetes, allergic/autoimmune and inflammatory disease are elucidated. Conclusion: Plants are one of the major sources of healthy dietary products, whose exploitation may promote prevention of chronic disease.

ACS Style

Thea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. Taking Advantage of Plant Defense Mechanisms to Promote Human Health. Exploitation of Plant Natural Products for Preventing or Treating Human Disease. Second of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets 2020, 21, 1 -16.

AMA Style

Thea Magrone, Manrico Magrone, Matteo Antonio Russo, Emilio Jirillo. Taking Advantage of Plant Defense Mechanisms to Promote Human Health. Exploitation of Plant Natural Products for Preventing or Treating Human Disease. Second of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2020; 21 ():1-16.

Chicago/Turabian Style

Thea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. 2020. "Taking Advantage of Plant Defense Mechanisms to Promote Human Health. Exploitation of Plant Natural Products for Preventing or Treating Human Disease. Second of Two Parts." Endocrine, Metabolic & Immune Disorders - Drug Targets 21, no. : 1-16.

Journal article
Published: 10 November 2020 in Current Stem Cell Research & Therapy
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Background: Substantial evidences support the hypothesis that the epicardium has a role in cardiac repair and regeneration in part providing, by epithelial to mesenchymal transition (EMT), progenitor cells that differentiate into cardiac cell types and in part releasing paracrine factors that contribute to cardiac repair. Besides cell contribution, a significant paracrine communication occurs between the epicardium and the myocardium that improves the whole regenerative response. Signaling pathways underlying this communication are multiple as well as soluble factors involved in cardiac repair and secreted both by myocardial and epicardial cells. Most recently, extracellular vesicles, i.e. exosomes, that accumulate in the pericardial fluid (PF) and are able to transport bioactive molecules (cytosolic proteins, mRNAs, miRNAs and other non-coding RNAs), have been also identified as potential mediators of epicardial-mediated repair following myocardial injury. Conclusions: This mini-review provides an overview of the epicardial-myocardial signaling in regulating cardiac repair in ischemic heart diseases. Indeed, a detailed understanding of the crosstalk between myocardial and epicardial cells and how paracrine mechanisms are involved in the context of ischemic heart diseases would be of tremendous help in developing novel therapeutic approaches to promote cardiomyocytes survival and heart regeneration following myocardial infarction (MI).

ACS Style

Laura Pellegrini; Eleonora Foglio; Elena Pontemezzo; Antonia Germani; Matteo Antonio Russo; Federica Limana. Cardiac Repair: The Intricate Crosstalk between the Epicardium and the Myocardium. Current Stem Cell Research & Therapy 2020, 15, 661 -673.

AMA Style

Laura Pellegrini, Eleonora Foglio, Elena Pontemezzo, Antonia Germani, Matteo Antonio Russo, Federica Limana. Cardiac Repair: The Intricate Crosstalk between the Epicardium and the Myocardium. Current Stem Cell Research & Therapy. 2020; 15 (8):661-673.

Chicago/Turabian Style

Laura Pellegrini; Eleonora Foglio; Elena Pontemezzo; Antonia Germani; Matteo Antonio Russo; Federica Limana. 2020. "Cardiac Repair: The Intricate Crosstalk between the Epicardium and the Myocardium." Current Stem Cell Research & Therapy 15, no. 8: 661-673.

Journal article
Published: 09 November 2020 in Antioxidants
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Neuropathic pain is a chronic painful disease. Data have shown that reactive oxygen species (ROS) are implicated in chronic pain. Particularly, the enhanced ROS production alters the mitochondrial genome and proteome through the accumulation of lipid peroxidation products, such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). Sirtuin 3 (SIRT3) is a mitochondrial protein and its activity can reduce ROS levels by modulating key antioxidant enzymes, such as manganese superoxide dismutase (MnSOD). Here, we evaluated the role of SIRT3 in the maintenance of basal levels of ROS in a model of chronic constriction injury (CCI) of the sciatic nerve and the protective effects of a natural antioxidant, the bergamot polyphenolic fraction (BPF). Rats were exposed to CCI of the sciatic nerve in the presence or absence of BPF (25–75 mg/kg). Level of acetylation, post-translational modulation on cysteine residues of proteins by HNE and SIRT3 activation, were detected in the spinal cord through western blotting, WES methodology and enzymatic assays. Our results reported that SIRT3 carbonylation and therefore its inactivation contributes to mitochondrial MnSOD hyperacetylation during CCI induced neuropathic pain in rats. In particular, we have demonstrated a close relation between oxidative stress, hyperalgesia, allodynia and sirtuins inactivation reverted by BPF administration.

ACS Style

Sara Ilari; Luigino Antonio Giancotti; Filomena Lauro; Micaela Gliozzi; Valentina Malafoglia; Ernesto Palma; Marco Tafani; Matteo Antonio Russo; Carlo Tomino; Massimo Fini; Daniela Salvemini; Vincenzo Mollace; Carolina Muscoli. Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway. Antioxidants 2020, 9, 1103 .

AMA Style

Sara Ilari, Luigino Antonio Giancotti, Filomena Lauro, Micaela Gliozzi, Valentina Malafoglia, Ernesto Palma, Marco Tafani, Matteo Antonio Russo, Carlo Tomino, Massimo Fini, Daniela Salvemini, Vincenzo Mollace, Carolina Muscoli. Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway. Antioxidants. 2020; 9 (11):1103.

Chicago/Turabian Style

Sara Ilari; Luigino Antonio Giancotti; Filomena Lauro; Micaela Gliozzi; Valentina Malafoglia; Ernesto Palma; Marco Tafani; Matteo Antonio Russo; Carlo Tomino; Massimo Fini; Daniela Salvemini; Vincenzo Mollace; Carolina Muscoli. 2020. "Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway." Antioxidants 9, no. 11: 1103.

Journal article
Published: 05 November 2020 in Endocrine, Metabolic & Immune Disorders - Drug Targets
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Background & Objectives: In old people, both innate and adaptive immune responses are impaired, thus leading to a condition of systemic inflamm-ageing, even including the involvement of the central nervous system (CNS). Aims: Here, main mechanisms of the immune ageing and neuro-inflammation will be discussed along with the dietary approaches for the modulation of age related diseases. Discussion: Neuroinflammation is caused by the passage of inflammatory mediators through the brain blood barrier to CNS. Then, in the brain, antigenic stimulation of microglia and/or its activation by peripheral cytokines lead to a robust production of free radicals with another wave of proinflammatory cytokines which, in turn, causes massive neuronal damage. Also, infiltrating T cells [T helper (h) and T cytotoxic cells] contribute to neuronal damage. Additionally, a peripheral imbalance between inflammatory Th17 cells and anti-inflammatory T regulatory cells seems to be prevalent in the aged brain, thus leading to a proinflammatory profile. Alzheimer’s disease, Parkinson’s disease and multiple sclerosis will be described as typical neurodegenerative diseases. Finally, modulation of the immune response thanks to the anti-oxidant and anti-inflammatory effects exerted by dietary products and nutraceuticals in ageing will be discussed. Special emphasis will be placed on polyunsaturated fatty acids, polyphenols, micronutrients and pre-probiotics and synbiotics. Conclusion: Ageing is characterized by an imbalance subversion of the immune system with a condition of inflamm-ageing. Neuroinflammation and neurodegenerative diseases seem to be a central manifestation of a peripheral perturbation of the immune machinery. Dietary products and nutraceuticals may lead to a down-regulation of the oxidative and pro-inflammatory profile in ageing.

ACS Style

Thea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. Peripheral Immunosenescence and Central Neuroinflammation: A Dangerous Liaison - A Dietary Approach. Endocrine, Metabolic & Immune Disorders - Drug Targets 2020, 20, 1391 -1411.

AMA Style

Thea Magrone, Manrico Magrone, Matteo A. Russo, Emilio Jirillo. Peripheral Immunosenescence and Central Neuroinflammation: A Dangerous Liaison - A Dietary Approach. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2020; 20 (9):1391-1411.

Chicago/Turabian Style

Thea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. 2020. "Peripheral Immunosenescence and Central Neuroinflammation: A Dangerous Liaison - A Dietary Approach." Endocrine, Metabolic & Immune Disorders - Drug Targets 20, no. 9: 1391-1411.

Journal article
Published: 09 September 2020 in Endocrine, Metabolic & Immune Disorders - Drug Targets
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Background: Heavy metals [arsenic, aluminium, cadmium, chromium, cobalt, lead, nickel (Ni), palladium and titanium] are environmental contaminants able to impact with host human cells, thus, leading to severe damage. Objective: In this review, the detrimental effects of several heavy metals on human organs will be discussed and special emphasis will be placed on Ni. In particular, Ni is able to interact with Toll-like receptor (TLR)-4 on immune and non immune cells, thus, triggering the cascade of pro-inflammatory cytokines. Then, inflammatory and allergic reactions mediated by Ni will be illustrated within different organs, even including the central nervous system, airways and the gastrointestinal system. Discussion: Different therapeutic strategies have been adopted to mitigate Ni-induced inflammatory-allergic reactions. In this context the ability of polyphenols to counteract the inflammatory pathway induced by Ni on peripheral blood leukocytes from Ni-sensitized patients will be outlined. In particular, polyphenols are able to decrease serum levels of interleukin (IL)-17, while increasing levels of IL-10. These data suggest that the equilibrium between T regulatory cells and T helper 17 cells is recovered with IL-10 acting as an anti-inflammatory cytokine. In the same context, polyphenols reduced elevated serum levels of nitric oxide, thus, expressing their anti-oxidant potential. Finally, the carcinogenic potential of heavy metals, even including Ni, will be highlighted. Conclusion: Heavy metals and, in particular, Ni are very spread in the environment. Nutritional approaches seem to represent a novel option in the treatment of Ni-induced damage and, among them, polyphenols should be taken into consideration for their anti-oxidant and anti-inflammatory activities.

ACS Style

Matteo Antonio Russo; Emilio Jirillo. Impact of heavy metals with host cells: Special focus on nickel-mediated pathologies and novel interventional approaches. Endocrine, Metabolic & Immune Disorders - Drug Targets 2020, 20, 1 -1.

AMA Style

Matteo Antonio Russo, Emilio Jirillo. Impact of heavy metals with host cells: Special focus on nickel-mediated pathologies and novel interventional approaches. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2020; 20 (7):1-1.

Chicago/Turabian Style

Matteo Antonio Russo; Emilio Jirillo. 2020. "Impact of heavy metals with host cells: Special focus on nickel-mediated pathologies and novel interventional approaches." Endocrine, Metabolic & Immune Disorders - Drug Targets 20, no. 7: 1-1.

Review
Published: 17 July 2020 in International Journal of Molecular Sciences
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Cardiomyopathies are myocardial disorders in which heart muscle is structurally and/or functionally abnormal. Previously, structural cardiomyocyte disorders due to adrenal diseases, such as hyperaldosteronism, hypercortisolism, and hypercatecholaminism, were misunderstood, and endomyocardial biopsy (EMB) was not performed because was considered dangerous and too invasive. Recent data confirm that, if performed in experienced centers, EMB is a safe technique and gives precious information about physiopathological processes implied in clinical abnormalities in patients with different systemic disturbances. In this review, we illustrate the most important features in patients affected by primary aldosteronism (PA), Cushing’s syndrome (CS), and pheochromocytoma (PHEO). Then, we critically describe microscopic and ultrastructural aspects that have emerged from the newest EMB studies. In PA, the autonomous hypersecretion of aldosterone induces the alteration of ion and water homeostasis, intracellular vacuolization, and swelling; interstitial oedema could be a peculiar feature of myocardial toxicity. In CS, cardiomyocyte hypertrophy and myofibrillolysis could be related to higher expression of atrogin-1. Finally, in PHEO, the hypercontraction of myofilaments with the formation of contraction bands and occasional cellular necrosis has been observed. We expect to clear the role of EMB in patients with cardiomyopathies and adrenal disease, and we believe EMB is a valid tool to implement new management and therapies.

ACS Style

Luigi Petramala; Antonio Concistrè; Federica Olmati; Vincenza Saracino; Cristina Chimenti; Andrea Frustaci; Matteo A. Russo; Claudio Letizia. Cardiomyopathies and Adrenal Diseases. International Journal of Molecular Sciences 2020, 21, 5047 .

AMA Style

Luigi Petramala, Antonio Concistrè, Federica Olmati, Vincenza Saracino, Cristina Chimenti, Andrea Frustaci, Matteo A. Russo, Claudio Letizia. Cardiomyopathies and Adrenal Diseases. International Journal of Molecular Sciences. 2020; 21 (14):5047.

Chicago/Turabian Style

Luigi Petramala; Antonio Concistrè; Federica Olmati; Vincenza Saracino; Cristina Chimenti; Andrea Frustaci; Matteo A. Russo; Claudio Letizia. 2020. "Cardiomyopathies and Adrenal Diseases." International Journal of Molecular Sciences 21, no. 14: 5047.

Journal article
Published: 11 April 2020 in International Journal of Molecular Sciences
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Tumor hypoxic microenvironment causes hypoxia inducible factor 1 alpha (HIF-1α) activation and necrosis with alarmins release. Importantly, HIF-1α also controls the expression of alarmin receptors in tumor cells that can bind to and be activated by alarmins. Human tumor tissues possess 1–2% of cancer stem cells (CSCs) residing in hypoxic niches and responsible for the metastatic potential of tumors. Our hypothesis is that hypoxic CSCs express alarmin receptors that can bind alarmins released during necrosis, an event favoring CSCs migration. To investigate this aspect, glioblastoma stem-like cell (GSC) lines were kept under hypoxia to determine the expression of hypoxic markers as well as receptor for advanced glycation end products (RAGE). The presence of necrotic extracts increased migration, invasion and cellular adhesion. Importantly, HIF-1α inhibition by digoxin or acriflavine prevented the response of GSCs to hypoxia alone or plus necrotic extracts. In vivo, GSCs injected in one brain hemisphere of NOD/SCID mice were induced to migrate to the other one in which a necrotic extract was previously injected. In conclusion, our results show that hypoxia is important not only for GSCs maintenance but also for guiding their response to external necrosis. Inhibition of hypoxic pathway may therefore represent a target for preventing brain invasion by glioblastoma stem cells (GSCs).

ACS Style

Marco Papale; Mariachiara Buccarelli; Cristiana Mollinari; Matteo A. Russo; Roberto Pallini; Lucia Ricci-Vitiani; Marco Tafani. Hypoxia, Inflammation and Necrosis as Determinants of Glioblastoma Cancer Stem Cells Progression. International Journal of Molecular Sciences 2020, 21, 2660 .

AMA Style

Marco Papale, Mariachiara Buccarelli, Cristiana Mollinari, Matteo A. Russo, Roberto Pallini, Lucia Ricci-Vitiani, Marco Tafani. Hypoxia, Inflammation and Necrosis as Determinants of Glioblastoma Cancer Stem Cells Progression. International Journal of Molecular Sciences. 2020; 21 (8):2660.

Chicago/Turabian Style

Marco Papale; Mariachiara Buccarelli; Cristiana Mollinari; Matteo A. Russo; Roberto Pallini; Lucia Ricci-Vitiani; Marco Tafani. 2020. "Hypoxia, Inflammation and Necrosis as Determinants of Glioblastoma Cancer Stem Cells Progression." International Journal of Molecular Sciences 21, no. 8: 2660.

Review
Published: 17 March 2020 in Applied Sciences
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Gravity is a constitutive force that influences life on Earth. It is sensed and translated into biochemical stimuli through the so called “mechanosensors”, proteins able to change their molecular conformation in order to amplify external cues causing several intracellular responses. Mechanosensors are widely represented in the human body with important structures such as otholiths in hair cells of vestibular system and statoliths in plants. Moreover, they are also present in the bone, where mechanical cues can cause bone resorption or formation and in muscle in which mechanical stimuli can increase the sensibility for mechanical stretch. In this review, we discuss the role of mechanosensors in two different conditions: normogravity and microgravity, emphasizing their emerging role in microgravity. Microgravity is a singular condition in which many molecular changes occur, strictly connected with the modified gravity force and free fall of bodies. Here, we first summarize the most important mechanosensors involved in normogravity and microgravity. Subsequently, we propose muscle LIM protein (MLP) and sirtuins as new actors in mechanosensing and signaling transduction under microgravity.

ACS Style

Michele Aventaggiato; Federica Barreca; Enza Vernucci; Mariano Bizzarri; Elisabetta Ferretti; Matteo A. Russo; Marco Tafani. Putative Receptors for Gravity Sensing in Mammalian Cells: The Effects of Microgravity. Applied Sciences 2020, 10, 2028 .

AMA Style

Michele Aventaggiato, Federica Barreca, Enza Vernucci, Mariano Bizzarri, Elisabetta Ferretti, Matteo A. Russo, Marco Tafani. Putative Receptors for Gravity Sensing in Mammalian Cells: The Effects of Microgravity. Applied Sciences. 2020; 10 (6):2028.

Chicago/Turabian Style

Michele Aventaggiato; Federica Barreca; Enza Vernucci; Mariano Bizzarri; Elisabetta Ferretti; Matteo A. Russo; Marco Tafani. 2020. "Putative Receptors for Gravity Sensing in Mammalian Cells: The Effects of Microgravity." Applied Sciences 10, no. 6: 2028.

Review
Published: 17 March 2020 in Cancers
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Cancer treatment has made significant progress in the cure of different types of tumors. Nevertheless, its clinical use is limited by unwanted cardiotoxicity. Aside from the conventional chemotherapy approaches, even the most newly developed, i.e., molecularly targeted therapy and immunotherapy, exhibit a similar frequency and severity of toxicities that range from subclinical ventricular dysfunction to severe cardiomyopathy and, ultimately, congestive heart failure. Specific mechanisms leading to cardiotoxicity still remain to be elucidated. For instance, oxidative stress and DNA damage are considered key players in mediating cardiotoxicity in different treatments. microRNAs (miRNAs) act as key regulators in cell proliferation, cell death, apoptosis, and cell differentiation. Their dysregulation has been associated with adverse cardiac remodeling and toxicity. This review provides an overview of the cardiotoxicity induced by different oncologic treatments and potential miRNAs involved in this effect that could be used as possible therapeutic targets.

ACS Style

Laura Pellegrini; Sara Sileno; Marco D’Agostino; Eleonora Foglio; Maria Cristina Florio; Vincenzo Guzzanti; Matteo Antonio Russo; Federica Limana; Alessandra Magenta. MicroRNAs in Cancer Treatment-Induced Cardiotoxicity. Cancers 2020, 12, 704 .

AMA Style

Laura Pellegrini, Sara Sileno, Marco D’Agostino, Eleonora Foglio, Maria Cristina Florio, Vincenzo Guzzanti, Matteo Antonio Russo, Federica Limana, Alessandra Magenta. MicroRNAs in Cancer Treatment-Induced Cardiotoxicity. Cancers. 2020; 12 (3):704.

Chicago/Turabian Style

Laura Pellegrini; Sara Sileno; Marco D’Agostino; Eleonora Foglio; Maria Cristina Florio; Vincenzo Guzzanti; Matteo Antonio Russo; Federica Limana; Alessandra Magenta. 2020. "MicroRNAs in Cancer Treatment-Induced Cardiotoxicity." Cancers 12, no. 3: 704.

Review
Published: 31 December 2019 in Antioxidants
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In this review, special emphasis will be placed on red grape polyphenols for their antioxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of proinflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Additionally, the effects of red grape polyphenols will be analyzed in obesity, as a low-grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood–brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great antioxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites, and interaction with microbiota, deserve deeper studies.

ACS Style

Thea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies. Antioxidants 2019, 9, 35 .

AMA Style

Thea Magrone, Manrico Magrone, Matteo Antonio Russo, Emilio Jirillo. Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies. Antioxidants. 2019; 9 (1):35.

Chicago/Turabian Style

Thea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. 2019. "Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies." Antioxidants 9, no. 1: 35.

Preprint
Published: 03 December 2019
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In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.

ACS Style

Thea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. Recent Advances on the Anti-inflammatory and Anti-oxidant properties of Red Grape Polyphenols: In Vitro and in Vivo Studies. 2019, 1 .

AMA Style

Thea Magrone, Manrico Magrone, Matteo Antonio Russo, Emilio Jirillo. Recent Advances on the Anti-inflammatory and Anti-oxidant properties of Red Grape Polyphenols: In Vitro and in Vivo Studies. . 2019; ():1.

Chicago/Turabian Style

Thea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. 2019. "Recent Advances on the Anti-inflammatory and Anti-oxidant properties of Red Grape Polyphenols: In Vitro and in Vivo Studies." , no. : 1.

Journal article
Published: 14 November 2019 in JCI Insight
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Cardiomyopathies are complex heart muscle diseases that can be inherited or acquired. Dilated cardiomyopathy can result from mutations in LMNA, encoding the nuclear intermediate filament proteins lamin A/C. Some LMNA mutations lead to accumulation of the lamin A precursor, prelamin A, which is disease causing in a number of tissues, yet its impact upon the heart is unknown. Here, we discovered myocardial prelamin A accumulation occurred in a case of dilated cardiomyopathy, and we show that a potentially novel mouse model of cardiac-specific prelamin A accumulation exhibited a phenotype consistent with inflammatory cardiomyopathy, which we observed to be similar to HIV-associated cardiomyopathy, an acquired disease state. Numerous HIV protease therapies are known to inhibit ZMPSTE24, the enzyme responsible for prelamin A processing, and we confirmed that accumulation of prelamin A occurred in HIV+ patient cardiac biopsies. These findings (a) confirm a unifying pathological role for prelamin A common to genetic and acquired cardiomyopathies; (b) have implications for the management of HIV patients with cardiac disease, suggesting protease inhibitors should be replaced with alternative therapies (i.e., nonnucleoside reverse transcriptase inhibitors); and (c) suggest that targeting inflammation may be a useful treatment strategy for certain forms of inherited cardiomyopathy.

ACS Style

Daniel Brayson; Andrea Frustaci; Romina Verardo; Cristina Chimenti; Matteo Antonio Russo; Robert Hayward; Sadia Munir Ahmad; Gema Vizcay-Barrena; Andrea Protti; Peter S. Zammit; Cristobal G. Dos Remedios; Elisabeth Ehler; Ajay M. Shah; Catherine M. Shanahan. Prelamin A mediates myocardial inflammation in dilated and HIV-associated cardiomyopathies. JCI Insight 2019, 4, 1 .

AMA Style

Daniel Brayson, Andrea Frustaci, Romina Verardo, Cristina Chimenti, Matteo Antonio Russo, Robert Hayward, Sadia Munir Ahmad, Gema Vizcay-Barrena, Andrea Protti, Peter S. Zammit, Cristobal G. Dos Remedios, Elisabeth Ehler, Ajay M. Shah, Catherine M. Shanahan. Prelamin A mediates myocardial inflammation in dilated and HIV-associated cardiomyopathies. JCI Insight. 2019; 4 (22):1.

Chicago/Turabian Style

Daniel Brayson; Andrea Frustaci; Romina Verardo; Cristina Chimenti; Matteo Antonio Russo; Robert Hayward; Sadia Munir Ahmad; Gema Vizcay-Barrena; Andrea Protti; Peter S. Zammit; Cristobal G. Dos Remedios; Elisabeth Ehler; Ajay M. Shah; Catherine M. Shanahan. 2019. "Prelamin A mediates myocardial inflammation in dilated and HIV-associated cardiomyopathies." JCI Insight 4, no. 22: 1.

Review article
Published: 26 June 2019 in Oxidative Medicine and Cellular Longevity
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Amyloidoses are heterogeneous diseases that result from the deposition of toxic insoluble β-sheet fibrillar protein aggregates in different tissues. The cascade of molecular events leading to amyloidoses and to the related clinical manifestations is not completely understood. Nevertheless, it is known that tissue damage associated to this disease involves alteration of tissue architecture, interaction with cell surface receptors, inflammation elicited by the amyloid protein deposition, oxidative stress, and apoptosis. However, another important aspect to consider is that systemic protein massive deposition not only subverts tissue architecture but also determines a progressive cellular hypertrophy and dilation of the extracellular space enlarging the volume of the organ. Such an alteration increases the distance between cells and vessels with a drop in pO2 that, in turn, causes both necrotic cell death and activation of the hypoxia transcription factor HIF-1α. Herewith, we propose the hypothesis that both cell death and hypoxia represent two important events for the pathogenesis of damage and progression of amyloidoses. In fact, molecules released by necrotic cells activate inflammatory cells from one side while binding to HIF-1α-dependent membrane receptors expressed on hypoxic parenchymal cells on the other side. This latter event generates a signaling cascade triggering NFκB activation and chronic inflammation. Finally, we also suggest that this scenario, once proved and detailed, might suggest important targets for new therapeutic interventions.

ACS Style

Matteo A. Russo; Carlo Tomino; Enza Vernucci; Federica Limana; Luigi Sansone; Andrea Frustaci; Marco Tafani. Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic Targets. Oxidative Medicine and Cellular Longevity 2019, 2019, 7935310 -10.

AMA Style

Matteo A. Russo, Carlo Tomino, Enza Vernucci, Federica Limana, Luigi Sansone, Andrea Frustaci, Marco Tafani. Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic Targets. Oxidative Medicine and Cellular Longevity. 2019; 2019 ():7935310-10.

Chicago/Turabian Style

Matteo A. Russo; Carlo Tomino; Enza Vernucci; Federica Limana; Luigi Sansone; Andrea Frustaci; Marco Tafani. 2019. "Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic Targets." Oxidative Medicine and Cellular Longevity 2019, no. : 7935310-10.

Journal article
Published: 12 June 2019 in Molecules
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In mice, postnatal immune development has previously been investigated, and evidence of a delayed maturation of the adaptive immune response has been detected. In this study, the effects of red grape polyphenol oral administration on the murine immune response were explored using pregnant mice (TAG/F3 transgenic and wild type (wt) mice) as the animal model. The study was performed during pregnancy as well as during lactation until postnatal day 8. Suckling pups from polyphenol-administered dams as well as day 30 post-weaning pups (dietary-administered with polyphenols) were used. Polyphenol effects were evaluated, measuring splenic cytokine secretion. Phorbol myristate acetate-activated splenocytes underwent the highest cytokine production at day 30 in both wt and TAG/F3 mice. In the latter, release of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was found to be higher than in the wt counterpart. In this context, polyphenols exerted modulating activities on day 30 TAG/F3 mice, inducing release of interleukin (IL)-10 in hetero mice while abrogating release of IL-2, IFN-γ, TNF-α, IL-6, and IL-4 in homo and hetero mice. Polyphenols are able to prevent the development of an inflammatory/allergic profile in postnatal TAG/F3 mice.

ACS Style

Thea Magrone; Anna Spagnoletta; Antonella Bizzoca; Matteo Antonio Russo; Emilio Jirillo; Gianfranco Gennarini. Polyphenol Effects on Splenic Cytokine Response in Post-Weaning Contactin 1-Overexpressing Transgenic Mice. Molecules 2019, 24, 2205 .

AMA Style

Thea Magrone, Anna Spagnoletta, Antonella Bizzoca, Matteo Antonio Russo, Emilio Jirillo, Gianfranco Gennarini. Polyphenol Effects on Splenic Cytokine Response in Post-Weaning Contactin 1-Overexpressing Transgenic Mice. Molecules. 2019; 24 (12):2205.

Chicago/Turabian Style

Thea Magrone; Anna Spagnoletta; Antonella Bizzoca; Matteo Antonio Russo; Emilio Jirillo; Gianfranco Gennarini. 2019. "Polyphenol Effects on Splenic Cytokine Response in Post-Weaning Contactin 1-Overexpressing Transgenic Mice." Molecules 24, no. 12: 2205.

Review article
Published: 09 May 2019 in Oxidative Medicine and Cellular Longevity
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Mitochondria are the cellular center of energy production and of several important metabolic processes. Mitochondrion health is maintained with a substantial intervention of mitophagy, a process of macroautophagy that degrades selectively dysfunctional and irreversibly damaged organelles. Because of its crucial duty, alteration in mitophagy can cause functional and structural adjustment in the mitochondria, changes in energy production, loss of cellular adaptation, and cell death. In this review, we discuss the dual role that mitophagy plays in cancer and age-related pathologies, as a consequence of oxidative stress, evidencing the triggering stimuli and mechanisms and suggesting the molecular targets for its therapeutic control. Finally, a section has been dedicated to the interplay between mitophagy and therapies using nanoparticles that are the new frontier for a direct and less invasive strategy.

ACS Style

Enza Vernucci; Carlo Tomino; Francesca Molinari; Dolores Limongi; Michele Aventaggiato; Luigi Sansone; Marco Tafani; Matteo A. Russo. Mitophagy and Oxidative Stress in Cancer and Aging: Focus on Sirtuins and Nanomaterials. Oxidative Medicine and Cellular Longevity 2019, 2019, 1 -19.

AMA Style

Enza Vernucci, Carlo Tomino, Francesca Molinari, Dolores Limongi, Michele Aventaggiato, Luigi Sansone, Marco Tafani, Matteo A. Russo. Mitophagy and Oxidative Stress in Cancer and Aging: Focus on Sirtuins and Nanomaterials. Oxidative Medicine and Cellular Longevity. 2019; 2019 ():1-19.

Chicago/Turabian Style

Enza Vernucci; Carlo Tomino; Francesca Molinari; Dolores Limongi; Michele Aventaggiato; Luigi Sansone; Marco Tafani; Matteo A. Russo. 2019. "Mitophagy and Oxidative Stress in Cancer and Aging: Focus on Sirtuins and Nanomaterials." Oxidative Medicine and Cellular Longevity 2019, no. : 1-19.