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Author Emanuela Ricciotti

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Anti-Migratory Effects of 4'-Geranyloxyferulic Acid on LPS-Stimulated U937 and HCT116 Cells via MMP-9 Down-Regulation: Involvement of ROS/ERK Signaling Pathway.

Sara Franceschelli, Daniela Maria Pia Gatta, Alessio Ferrone, Giulia Mezza, Lorenza Speranza, Mirko Pesce, Alfredo Grilli, Marialucia Gallorini, Viviana Di Giacomo, Barbara Ghinassi, Serena Fiorito, Salvatore Genovese, Emanuela Ricciotti, Mario Felaco, Antonia Patruno,

Matrix metalloproteinases (MMPs) play a crucial role in tumor angiogenesis, and metastasis. 4'-geranyloxyferulic acid (GOFA) has anti-tumor and anti-inflammatory proprieties. Herein, we aimed to determine whether this compound affects cell survival, invasion, and migration through reactive oxygen species (ROS)-mediated MMPs activation of extracellular signal-regulated kinases (ERKs) and p38 signaling in ... Read more >>

Antioxidants (Basel) (Antioxidants (Basel, Switzerland))
[2020, 9(6):]

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Pharmacological Characterization of the Microsomal Prostaglandin E2 Synthase-1 Inhibitor AF3485 In Vitro and In Vivo.

Luigia Di Francesco, Annalisa Bruno, Emanuela Ricciotti, Stefania Tacconelli, Melania Dovizio, Paloma Guillem-Llobat, Maria Alessandra Alisi, Beatrice Garrone, Isabella Coletta, Giorgina Mangano, Claudio Milanese, Garret A FitzGerald, Paola Patrignani,

Rationale:The development of inhibitors of microsomal prostaglandin (PG)E2 synthase-1 (mPGES-1) was driven by the promise of attaining antiinflammatory agents with a safe cardiovascular profile because of the possible diversion of the accumulated substrate, PGH2, towards prostacyclin (PGI2). Objectives:We studied the effect of the human mPGES-1 inhibitor, AF3485 (a benzamide derivative) ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2020, 11:374]

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Sex dependent compensatory mechanisms to preserve blood pressure homeostasis in PGI2 receptor deficient mice

Soon Yew Tang, Seán Anderson, Hu Meng, Dimitra Sarantopoulou, Emanuela Ricciotti, Elizabeth Hennessy, Gregory Grant, Garret FitzGerald,

Abstract Inhibitors of microsomal prostaglandin E synthase-1 (mPges-1) are in the early phase of clinical development. Deletion of mPges-1 confers analgesia, restrains atherogenesis and fails to accelerate thrombogenesis, while suppressing prostaglandin (PG) E 2 , but increasing biosynthesis of prostacyclin (PGI 2 ). In hyperlipidemic mice, this last effect represents ... Read more >>

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Prostaglandin regulation of T cell biology.

Damian Maseda, Emanuela Ricciotti, Leslie J Crofford,

Prostaglandins (PG) are pleiotropic bioactive lipids involved in the control of many physiological processes, including key roles in regulating inflammation. This links PG to the modulation of the quality and magnitude of immune responses. T cells, as a core part of the immune system, respond readily to inflammatory cues from ... Read more >>

Pharmacol. Res. (Pharmacological research)
[2019, 149:104456]

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Platelet-Specific Deletion of Cyclooxygenase-1 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice.

Angela Sacco, Annalisa Bruno, Annalisa Contursi, Melania Dovizio, Stefania Tacconelli, Emanuela Ricciotti, Paloma Guillem-Llobat, Tania Salvatore, Luigia Di Francesco, Rosa Fullone, Patrizia Ballerini, Vincenzo Arena, Sara Alberti, Guizhu Liu, Yanjun Gong, Alessandro Sgambato, Carlo Patrono, Garret A FitzGerald, Ying Yu, Paola Patrignani,

Inflammatory bowel disease (IBD) is associated with an increased risk for thromboembolism, platelet activation, and abnormalities in platelet number and size. In colitis, platelets can extravasate into the colonic interstitium. We generated a mouse with a specific deletion of cyclooxygenase (COX)-1 in megakaryocytes/platelets [(COX-1 conditional knockout (cKO)] to clarify the ... Read more >>

J. Pharmacol. Exp. Ther. (The Journal of pharmacology and experimental therapeutics)
[2019, 370(3):416-426]

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Comparative evaluation of RNA-Seq library preparation methods for strand-specificity and low input.

Dimitra Sarantopoulou, Soon Yew Tang, Emanuela Ricciotti, Nicholas F Lahens, Damien Lekkas, Jonathan Schug, Xiaofeng S Guo, Georgios K Paschos, Garret A FitzGerald, Allan I Pack, Gregory R Grant,

Library preparation is a key step in sequencing. For RNA sequencing there are advantages to both strand specificity and working with minute starting material, yet until recently there was no kit available enabling both. The Illumina TruSeq stranded mRNA Sample Preparation kit (TruSeq) requires abundant starting material while the Takara Bio SMART-Seq ... Read more >>

Sci Rep (Scientific reports)
[2019, 9(1):13477]

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Modulation of Apoptotic Cell Death and Neuroprotective Effects of Glutathione-L-Dopa Codrug Against H2O2-Induced Cellular Toxicity.

Sara Franceschelli, Paola Lanuti, Alessio Ferrone, Daniela Maria Pia Gatta, Lorenza Speranza, Mirko Pesce, Alfredo Grilli, Ivana Cacciatore, Emanuela Ricciotti, Antonio Di Stefano, Sebastiano Miscia, Mario Felaco, Antonia Patruno,

The L-3,4-dihydroxyphenylalanine (LD) is the gold standard drug currently used to manage Parkinson's disease (PD) and to control its symptoms. However, LD could cause disease neurotoxicity due to the generation of pro-oxidant intermediates deriving from its autoxidation. In order to overcome this limitation, we have conjugated LD to the natural ... Read more >>

Antioxidants (Basel) (Antioxidants (Basel, Switzerland))
[2019, 8(8):]

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Fatty acid transport protein 2 reprograms neutrophils in cancer.

Filippo Veglia, Vladimir A Tyurin, Maria Blasi, Alessandra De Leo, Andrew V Kossenkov, Laxminarasimha Donthireddy, Tsun Ki Jerrick To, Zach Schug, Subhasree Basu, Fang Wang, Emanuela Ricciotti, Concetta DiRusso, Maureen E Murphy, Robert H Vonderheide, Paul M Lieberman, Charles Mulligan, Brian Nam, Neil Hockstein, Gregory Masters, Michael Guarino, Cindy Lin, Yulia Nefedova, Paul Black, Valerian E Kagan, Dmitry I Gabrilovich,

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are pathologically activated neutrophils that are crucial for the regulation of immune responses in cancer. These cells contribute to the failure of cancer therapies and are associated with poor clinical outcomes. Despite recent advances in the understanding of PMN-MDSC biology, the mechanisms responsible for the ... Read more >>

Nature (Nature)
[2019, 569(7754):73-78]

Cited: 8 times

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Distinct vascular genomic response of proton and gamma radiation

Ricciotti Emanuela, Dimitra Sarantopoulou, Gregory Grant, Jenine Sanzari, Gabriel Krigsfeld, Amber Kiliti, Ann Kennedy, Tilo Grosser,

Abstract Purpose . The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge. Materials and methods. We performed comparative RNA sequencing of the aorta following (4 ... Read more >>

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Lipocalin-Like Prostaglandin D Synthase but Not Hemopoietic Prostaglandin D Synthase Deletion Causes Hypertension and Accelerates Thrombogenesis in Mice.

Wen-Liang Song, Emanuela Ricciotti, Xue Liang, Tilo Grosser, Gregory R Grant, Garret A FitzGerald,

Prostaglandin (PG) D2 is formed by two distinct PGD synthases (PGDS): lipocalin-type PGDS (L-PGDS), which acts as a PGD2-producing enzyme and as extracellular lipophilic transporter, and hematopoietic PGDS (H-PGDS), a σ glutathione-S-transferase. PGD2 plays an important role in the maintenance of vascular function; however, the relative contribution of L-PGDS- and ... Read more >>

J. Pharmacol. Exp. Ther. (The Journal of pharmacology and experimental therapeutics)
[2018, 367(3):425-432]

Cited: 1 time

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COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer.

Rachana Garg, Jorge M Blando, Carlos J Perez, Priti Lal, Michael D Feldman, Emer M Smyth, Emanuela Ricciotti, Tilo Grosser, Fernando Benavides, Marcelo G Kazanietz,

The pro-oncogenic kinase PKCε is overexpressed in human prostate cancer and cooperates with loss of the tumor suppressor Pten for the development of prostatic adenocarcinoma. However, the effectors driving PKCε-mediated phenotypes remain poorly defined. Here, using cellular and mouse models, we showed that PKCε overexpression acts synergistically with Pten loss ... Read more >>

Oncogene (Oncogene)
[2018, 37(34):4735-4749]

Cited: 4 times

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ISO-RELEVANCE FUNCTIONS - A SYSTEMATIC APPROACH TO RANKING GENOMIC FEATURES BY DIFFERENTIAL EFFECT SIZE

Soumyashant Nayak, Nicholas Lahens, Eun Ji Kim, Emanuela Ricciotti, George Paschos, Sarah Tishkoff, Dimitra Sarantopoulou, Shaon Sengupta, Barry Cooperman, Tilo Grosser, Gregory Grant,

Abstract It is common to measure large numbers of features to identify those differing between experimental conditions; for example using RNA-Seq to search for differentially expressed genes. Ranking by p-value allows for statistical control, but has well known issues: unreliability without many replicates; and significance of biologically irrelevant effect sizes. ... Read more >>

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The Cardiovascular Pharmacology of Nonsteroidal Anti-Inflammatory Drugs.

Tilo Grosser, Emanuela Ricciotti, Garret A FitzGerald,

The principal molecular mechanisms underlying the cardiovascular (CV) and renal adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs), such as myocardial infarction and hypertension, are understood in more detail than most side effects of drugs. Less is known, however, about differences in the CV safety profile between chemically distinct NSAIDs and ... Read more >>

Trends Pharmacol. Sci. (Trends in pharmacological sciences)
[2017, 38(8):733-748]

Cited: 11 times

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A comparison of Illumina and Ion Torrent sequencing platforms in the context of differential gene expression.

Nicholas F Lahens, Emanuela Ricciotti, Olga Smirnova, Erik Toorens, Eun Ji Kim, Giacomo Baruzzo, Katharina E Hayer, Tapan Ganguly, Jonathan Schug, Gregory R Grant,

Though Illumina has largely dominated the RNA-Seq field, the simultaneous availability of Ion Torrent has left scientists wondering which platform is most effective for differential gene expression (DGE) analysis. Previous investigations of this question have typically used reference samples derived from cell lines and brain tissue, and do not involve ... Read more >>

BMC Genomics (BMC Genomics)
[2017, 18(1):602]

Cited: 7 times

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Aspirin prevents colorectal cancer metastasis in mice by splitting the crosstalk between platelets and tumor cells.

Paloma Guillem-Llobat, Melania Dovizio, Annalisa Bruno, Emanuela Ricciotti, Valerio Cufino, Angela Sacco, Rosalia Grande, Sara Alberti, Vincenzo Arena, Mariangela Cirillo, Carlo Patrono, Garret A FitzGerald, Dieter Steinhilber, Alessandro Sgambato, Paola Patrignani,

We investigated whether platelets prime colon cancer cells for metastasis and whether pharmacological inhibition of platelet function may prevent it. Coculturing HT29 human colon carcinoma cells with human platelets led to the induction of mesenchymal-like cancer cells characterized by downregulation of E-cadherin and upregulation of Twist1, enhanced cell mobility and ... Read more >>

Oncotarget (Oncotarget)
[2016, 7(22):32462-32477]

Cited: 47 times

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Understanding multicellular function and disease with human tissue-specific networks.

Casey S Greene, Arjun Krishnan, Aaron K Wong, Emanuela Ricciotti, Rene A Zelaya, Daniel S Himmelstein, Ran Zhang, Boris M Hartmann, Elena Zaslavsky, Stuart C Sealfon, Daniel I Chasman, Garret A FitzGerald, Kara Dolinski, Tilo Grosser, Olga G Troyanskaya,

Tissue and cell-type identity lie at the core of human physiology and disease. Understanding the genetic underpinnings of complex tissues and individual cell lineages is crucial for developing improved diagnostics and therapeutics. We present genome-wide functional interaction networks for 144 human tissues and cell types developed using a data-driven Bayesian ... Read more >>

Nat. Genet. (Nature genetics)
[2015, 47(6):569-576]

Cited: 208 times

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COX-2, the dominant source of prostacyclin.

Emanuela Ricciotti, Ying Yu, Tilo Grosser, Garret A Fitzgerald,

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2013, 110(3):E183]

Cited: 16 times

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Mechanistic and pharmacological issues of aspirin as an anticancer agent.

Melania Dovizio, Stefania Tacconelli, Carlos Sostres, Emanuela Ricciotti, Paola Patrignani,

Recent findings have shown that aspirin, taken for several years, reduces the long-term risk of some cancers, particularly colorectal cancer. The result that aspirin benefit is detectable at daily low-doses (at least 75mg), the same used for the prevention of cardiovascular disease, positions the antiplatelet action of aspirin at the ... Read more >>

Pharmaceuticals (Basel) (Pharmaceuticals (Basel, Switzerland))
[2012, 5(12):1346-1371]

Cited: 22 times

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Disruption of the 5-lipoxygenase pathway attenuates atherogenesis consequent to COX-2 deletion in mice.

Zhou Yu, Irene Crichton, Soon Yew Tang, Yiqun Hui, Emanuela Ricciotti, Mark D Levin, John A Lawson, Ellen Puré, Garret A FitzGerald,

Suppression of cyclooxygenase 2 (COX-2)-derived prostacyclin (PGI(2)) is sufficient to explain most elements of the cardiovascular hazard from nonsteroidal antinflammatory drugs (NSAIDs). However, randomized trials are consistent with the emergence of cardiovascular risk during chronic dosing with NSAIDs. Although deletion of the PGI(2) receptor fosters atherogenesis, the importance of COX-2 ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2012, 109(17):6727-6732]

Cited: 24 times

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Novel aminobenzyl-acetamidine derivative modulate the differential regulation of NOSs in LPS induced inflammatory response: role of PI3K/Akt pathway.

Antonia Patruno, Sara Franceschelli, Mirko Pesce, Cristina Maccallini, Marialuigia Fantacuzzi, Lorenza Speranza, Alessio Ferrone, Maria Anna De Lutiis, Emanuela Ricciotti, Rosa Amoroso, Mario Felaco,

Previous reports suggest that NO may contribute to the pathophysiology of septic shock. Recently, we have synthesized and characterized a series of benzyl- and dibenzyl derivative of N-(3-aminobenzyl)acetamidine, a potent and selective inhibitor of iNOS, in vitro assay. We evaluated the molecular mechanisms by which these compounds are involved in ... Read more >>

Biochim. Biophys. Acta (Biochimica et biophysica acta)
[2012, 1820(12):2095-2104]

Cited: 23 times

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Vascular COX-2 modulates blood pressure and thrombosis in mice.

Ying Yu, Emanuela Ricciotti, Rosario Scalia, Soon Yew Tang, Gregory Grant, Zhou Yu, Gavin Landesberg, Irene Crichton, Weichen Wu, Ellen Puré, Colin D Funk, Garret A FitzGerald,

Prostacyclin (PGI(2)) is a vasodilator and platelet inhibitor, properties consistent with cardioprotection. More than a decade ago, inhibition of cyclooxygenase-2 (COX-2) by the nonsteroidal anti-inflammatory drugs (NSAIDs) rofecoxib and celecoxib was found to reduce the amount of the major metabolite of PGI(2) (PGI-M) in the urine of healthy volunteers. This ... Read more >>

Sci Transl Med (Science translational medicine)
[2012, 4(132):132ra54]

Cited: 81 times

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Niacin and biosynthesis of PGD₂by platelet COX-1 in mice and humans.

Wen-Liang Song, Jane Stubbe, Emanuela Ricciotti, Naji Alamuddin, Salam Ibrahim, Irene Crichton, Maxwell Prempeh, John A Lawson, Robert L Wilensky, Lars Melholt Rasmussen, Ellen Puré, Garret A FitzGerald,

The clinical use of niacin to treat dyslipidemic conditions is limited by noxious side effects, most commonly facial flushing. In mice, niacin-induced flushing results from COX-1-dependent formation of PGD₂ and PGE₂ followed by COX-2-dependent production of PGE₂. Consistent with this, niacin-induced flushing in humans is attenuated when niacin is combined ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2012, 122(4):1459-1468]

Cited: 26 times

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Effects of celecoxib on prostanoid biosynthesis and circulating angiogenesis proteins in familial adenomatous polyposis.

Melania Dovizio, Stefania Tacconelli, Emanuela Ricciotti, Annalisa Bruno, Thorsten Jürgen Maier, Paola Anzellotti, Luigia Di Francesco, Paola Sala, Stefano Signoroni, Lucio Bertario, Dan A Dixon, John A Lawson, Dieter Steinhilber, Garret A FitzGerald, Paola Patrignani,

Vascular cyclooxygenase (COX)-2-dependent prostacyclin (PGI(2)) may affect angiogenesis by preventing endothelial activation and platelet release of angiogenic factors present in platelet α-granules. Thus, a profound inhibition of COX-2-dependent PGI(2) might be associated with changes in circulating markers of angiogenesis. We aimed to address this issue by performing a clinical study ... Read more >>

J. Pharmacol. Exp. Ther. (The Journal of pharmacology and experimental therapeutics)
[2012, 341(1):242-250]

Cited: 13 times

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Prostaglandins and inflammation.

Emanuela Ricciotti, Garret A FitzGerald,

Prostaglandins are lipid autacoids derived from arachidonic acid. They both sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. They are generated from arachidonate by the action of cyclooxygenase isoenzymes, and their biosynthesis is blocked by nonsteroidal antiinflammatory drugs, including those selective for inhibition of cyclooxygenase-2. Despite the ... Read more >>

Arterioscler. Thromb. Vasc. Biol. (Arteriosclerosis, thrombosis, and vascular biology)
[2011, 31(5):986-1000]

Cited: 823 times

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NCX 4040, a nitric oxide-donating aspirin, exerts anti-inflammatory effects through inhibition of I kappa B-alpha degradation in human monocytes.

Emanuela Ricciotti, Melania Dovizio, Luigia Di Francesco, Paola Anzellotti, Tania Salvatore, Andrea Di Francesco, Maria G Sciulli, Giuseppa Pistritto, Angela Monopoli, Paola Patrignani,

NO-donating aspirins consist of aspirin to which a NO-donating group is covalently linked via a spacer molecule. NCX 4040 and NCX 4016 are positional isomers with respect to the -CH(2)ONO(2) group (para and meta, respectively) on the benzene ring of the spacer. Because positional isomerism is critical for antitumor properties ... Read more >>

J. Immunol. (Journal of immunology (Baltimore, Md. : 1950))
[2010, 184(4):2140-2147]

Cited: 7 times

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