431 results on '"Fagone P"'
Search Results
2. No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells
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Mijatović Sanja, Pešić Milica, Mojić Marija, Banković Jasna, Miljković Đorđe, Fagone Paolo, Mangano Katia, Nicoletti Ferdinando, Mccubrey James, Tanić Nikola, and Maksimović-Ivanić Danijela
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chemosensitization ,non-small cell lung carcinoma cells ,saquinavir ,saquinavir-no ,tumor ,Biochemistry ,QD415-436 - Abstract
Background: The NO-modified form of the HIV inhibitor saquinavir (Saq-NO) inhibited the growth of a variety of cancer cell lines in vitro and in vivo more potently than the original compound in a nontoxic fashion. In addition, chemo- and immunosensitizing properties were observed. The aim of the present study was to evaluate its anticancer action against non-small cell lung carcinoma cells in their doxorubicin (DOXO) sensitive and resistant phenotype (NCI-H460 and NCI-H460/R). Methods: The viability of cells was analyzed by MTT and crystal violet assays. DR5 expression was estimated by real time RT-PCR and flow cytometry. Activity of P-glycoprotein (P-gp) pumps was evaluated by the Rho123 accumulation assay. Results: Saq-NO diminished the viability of lung cancer cells through induction of cell cycle arrest in the G0/G1 phase independently of the overexpression of the P-gp pumps. In addition, Saq-NO elevated or completely reconstituted the doxorubicin efficacy in NCI-H460 and NCI-H460/R, respectively. The chemosensitizing effect in DOXO resistant cells was a consequence of P-gp inhibition which was found to be more potent than that observed with dex-verapamil, a conventional inhibitor of P-gp. Sensitization to DOXO upon Saq-NO was accompanied by elevated DR5 expression, but the resistance to TRAIL was not abrogated. Conclusions: The NO-modified HIV inhibitor saquinavir displayed equal antiproliferative and chemosensitizing properties in DOXO sensitive and resistant non-small cell lung carcinoma cells, suggesting the importance of the evaluation of this drug as an antineoplastic agent.
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- 2013
3. Transcriptional upregulation of galectin-3 in multiple sclerosis
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Mangano, Katia, Petralia, Maria Cristina, Bella, Rita, Pennisi, Manuela, Muñoz-Valle, José Francisco, Hernández-Bello, Jorge, Nicoletti, Ferdinando, and Fagone, Paolo
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- 2023
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4. Serum and urinary levels of MIF, CD74, DDT and CXCR4 among patients with type 1 diabetes mellitus, type 2 diabetes and healthy individuals: Implications for further research
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Katia Mangano, Aristidis Diamantopoulos, Natalia G. Vallianou, Theodora Stratigou, Fotis Panagopoulos, Dimitris Kounatidis, Maria Dalamaga, Paolo Fagone, and Ferdinando Nicoletti
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Autoimmunity ,Cytokine ,Diabetes mellitus ,D-dopachrome tautomerase ,Inflammation ,Macrophage migration inhibitory factor ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
Background: Macrophage migration inhibitory factor (MIF) is a highly conserved cytokine with pleiotropic properties, mainly pro-inflammatory. MIF seems to exert its pro-inflammatory features by binding to its transmembrane cellular receptor CD74. MIF also has CXCR4, which acts as a co-receptor in this inflammatory process. Apart from MIF, D-dopachrome tautomerase (DDT) or MIF2, which belongs to the MIF superfamily, also binds to receptor CD74. Therefore, these molecules, MIF, CD74, DDT and CXCR4 are suggested to work together orchestrating an inflammatory process. Diabetes mellitus is characterised by chronic low-grade inflammation. Therefore, the aim of the present study was to evaluate serum and urinary levels of the aforementioned molecules among patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and among healthy controls. Methods: We enrolled 13 patients with T1DM, 74 patients with T2DM and 25 healthy individuals as controls. Levels of CD74, CXCR4, DDT, and MIF were measured using ELISA Kits according to the manufacturer's instructions. Results: We documented increased serum MIF levels together with higher urinary CD74 levels among patients with T1DM, when compared to patients with T2DM and healthy adults. In particular, patients with T1DM showed significantly increased levels of MIF compared to T2DM (p = 0.011) and healthy controls (p = 0.0093). CD74 in urine were significantly higher in patients with T1DM compared to those affected with T2DM (p = 0.0302) and healthy group (p = 0.0099). On the contrary, serum CD74 were similar among the three groups. No statistical differences were identified in CXCR4 levels both in serum and in urine of all groups. Patients with T2DM and overweight/obesity had increased urinary levels of CD74, when compared to lean patients with T2DM. Conclusion: The increased serum MIF levels and urinary CD74 levels among patients with T1DM may be attributed to the autoimmune milieu, which characterises patients with T1DM, when compared to patients with T2DM. These two findings merit further attention as they could pave the way for further research regarding the potential beneficial effects of inhibitors of MIF among patients with T1DM, especially in the early stages of T1DM. Finally, the role of inhibitors of MIF could be further explored in the context of obesity among patients with T2DM.
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- 2024
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5. Identification of Poliovirus Receptor-like 3 Protein as a Prognostic Factor in Triple-Negative Breast Cancer
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Gian Marco Leone, Katia Mangano, Salvatore Caponnetto, Paolo Fagone, and Ferdinando Nicoletti
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triple-negative breast cancer ,PVRL3 ,EZH2 ,immune checkpoint ,biomarker ,Cytology ,QH573-671 - Abstract
Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, with a bad prognosis and lack of targeted therapeutic options. Characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, TNBC is often associated with a significantly lower survival rate compared to other breast cancer subtypes. Our study aimed to explore the prognostic significance of 83 immune-related genes, by using transcriptomic data from the TCGA database. Our analysis identified the Poliovirus Receptor-Like 3 protein (PVRL3) as a critical negative prognostic marker in TNBC patients. Furthermore, we found that the Enhancer of Zeste Homolog 2 (EZH2), a well-known epigenetic regulator, plays a pivotal role in modulating PVRL3 levels in TNBC cancer cell lines expressing EZH2 along with high levels of PVRL3. The elucidation of the EZH2-PVRL3 regulatory axis provides valuable insights into the molecular mechanisms underlying TNBC aggressiveness and opens up potential pathways for personalized therapeutic intervention.
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- 2024
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6. Transcriptional landscape of SARS-CoV-2 infection dismantles pathogenic pathways activated by the virus, proposes unique sex-specific differences and predicts tailored therapeutic strategies
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Fagone, Paolo, Ciurleo, Rosella, Lombardo, Salvo Danilo, Iacobello, Carmelo, Palermo, Concetta Ilenia, Shoenfeld, Yehuda, Bendtzen, Klaus, Bramanti, Placido, and Nicoletti, Ferdinando
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Quantitative Biology - Cell Behavior - Abstract
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has posed a serious threat to global health. As no specific therapeutics are yet available to control disease evolution, more in-depth understanding of the pathogenic mechanisms induced by SARS-CoV-2 will help to characterize new targets for the management of COVID-19. The present study identified a specific set of biological pathways altered in primary human lung epithelium upon SARS-CoV-2 infection, and a comparison with SARS-CoV from the 2003 pandemic was studied. The transcriptomic profiles were also exploited as possible novel therapeutic targets, and anti-signature perturbation analysis predicted potential drugs to control disease progression. Among them, Mitogen-activated protein kinase kinase (MEK), serine-threonine kinase (AKT), mammalian target of rapamycin (mTOR) and I kappa B Kinase (IKK) inhibitors emerged as candidate drugs. Finally, sex-specific differences that may underlie the higher COVID-19 mortality in men are proposed.
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- 2020
7. Experimental and numerical evaluation of the compressive and shear behavior of unstabilized rammed earth
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Ávila, Fernando, Fagone, Mario, Gallego, Rafael, Puertas, Esther, and Ranocchiai, Giovanna
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- 2023
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8. Emerging Therapeutic Potential of Polyphenols from Geranium sanguineum L. in Viral Infections, Including SARS-CoV-2
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Silviya Abarova, Ralitza Alexova, Stela Dragomanova, Ayten Solak, Paolo Fagone, Katia Mangano, Maria Cristina Petralia, Ferdinando Nicoletti, Reni Kalfin, and Lyubka Tancheva
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Geranium sanguineum ,viral infection ,COVID-19 ,poliphenols ,Microbiology ,QR1-502 - Abstract
The existing literature supports the anti-inflammatory, antioxidant, and antiviral capacities of the polyphenol extracts derived from Geranium sanguineum L. These extracts exhibit potential in hindering viral replication by inhibiting enzymes like DNA polymerase and reverse transcriptase. The antiviral properties of G. sanguineum L. seem to complement its immunomodulatory effects, contributing to infection resolution. While preclinical studies on G. sanguineum L. suggest its potential effectiveness against COVID-19, there is still a lack of clinical evidence. Therefore, the polyphenols extracted from this herb warrant further investigation as a potential alternative for preventing and treating COVID-19 infections.
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- 2024
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9. Characterization of a small molecule modulator of inflammatory cytokine production
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Sagar B Kudchodkar, Paolo Fagone, Omkar U Kawalekar, Moonsup Jeong, Christine C Roberts, Hyojin Lee, Youngran Cho, Areum Gil, Yeeun Oh, Bohyun Jeon, Gee Ho Park, Young K Park, Ferdinando Nicoletti, Joel N Maslow, and Kar Muthumani
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GLS-1027 ,Pro-inflammatory cytokines ,Inflammation ,Th17 cells ,Type 1 diabetes mellitus ,NOD mice ,Medicine - Abstract
Abstract In the present study, the effect(s) of the immunomodulatory drug GLS-1027 on various cell types involved in inflammation were investigated. GLS-1027 reduced LPS-stimulated secretion of pro-inflammatory cytokines by macrophage or monocytic cells and cell lines. This reduction was likely due in part to decreased activation of NF-κB family transcription factors and inhibition of p38 MAPK signaling in GLS-1027-treated cells. Independent from its effects on macrophages, GLS-1027 inhibited dendritic cell maturation and differentiation of naïve CD4+ T cells into Th17 cells, reducing the production of typical pro-inflammatory cytokines associated with both processes. In vivo administration of GLS-1027 prevented the development of type 1 diabetes in NOD mice which correlated with reduced serum levels of IL17A in GLS-1027 treated animals and reduced ex vivo production of IL17A from both spleen and lymph-node cells. Overall, our data show that GLS-1027 can reduce inflammation through multiple actions, including the reduction of pro-inflammatory cytokine production by innate immune cells, the inhibition of dendritic cells maturation, and the inhibition of Th17 cells polarization.
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- 2022
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10. Characterization of a small molecule modulator of inflammatory cytokine production
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Kudchodkar, Sagar B, Fagone, Paolo, Kawalekar, Omkar U, Jeong, Moonsup, Roberts, Christine C, Lee, Hyojin, Cho, Youngran, Gil, Areum, Oh, Yeeun, Jeon, Bohyun, Park, Gee Ho, Park, Young K, Nicoletti, Ferdinando, Maslow, Joel N, and Muthumani, Kar
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- 2022
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11. Evaluation of the Involvement of Heme Oxygenase-1 Expression in Discoid Lupus Erythematosus Lesions
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Paolo Fagone, Eliana Piombino, Katia Mangano, Rocco De Pasquale, Ferdinando Nicoletti, and Rosario Caltabiano
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discoid lupus erythematosus ,HMOX1 ,inflammation ,skin diseases ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Discoid lupus erythematosus (DLE) is a chronic autoimmune disease that primarily affects the skin, causing red, scaly patches that may be disfiguring and can cause permanent scarring. This study aimed to investigate the potential clinical and therapeutic applications of heme oxygenase-1 (HMOX1) in the context of DLE. Immunohistochemical staining and bioinformatics analysis were performed on skin biopsy samples from DLE patients to examine the levels of HMOX1 and to correlate with markers of inflammation. Our study revealed a negative correlation between HMOX1 levels and the inflammatory status of DLE lesions, as well as an inverse correlation between HMOX1 levels and the infiltration of M1 macrophages and activated mastocytes. These findings suggest that HMOX1 plays a crucial role in the regulation of inflammation in DLE and could be a potential therapeutic target and biomarker for DLE.
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- 2023
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12. Clinical and Prognostic Significance of p-ANCA Positivity in Idiopathic Pulmonary Fibrosis: A Retrospective Observational Study
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Alessandro Libra, Giuseppe Muscato, Giuseppe Ielo, Lucia Spicuzza, Stefano Palmucci, Evelina Fagone, Mary Fruciano, Elisa Gili, Gianluca Sambataro, and Carlo Vancheri
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idiopathic pulmonary fibrosis ,ANCA ,vasculitis ,Microscopic Polyangiitis ,Rheumatoid Factor ,UIP pattern ,Medicine (General) ,R5-920 - Abstract
Perinuclear Anti Neutrophil Cytoplasmic Antibody (p-ANCA) is a serological marker of Microscopic Polyangiitis (MPA), a vasculitis associated with lung involvement potentially mimicking Idiopathic Pulmonary Fibrosis (IPF). In this study, we evaluated the role of p-ANCA in predicting clinical evolution and prognosis in a cohort of IPF patients. In this observational, retrospective, case–control study, we compared 18 patients with an IPF diagnosis and p-ANCA positivity with 36 patients with seronegative IPF, matched for age and sex. IPF patients with and without p-ANCA showed similar lung function decline during the follow-up, but IPF p-ANCA+ showed better survival. Half of IPF p-ANCA+ patients were classified as MPA for the development of renal involvement (55%) or skin signs (45%). The progression towards MPA was associated with high levels of Rheumatoid Factor (RF) at baseline. In conclusion, p-ANCA, mainly when associated with RF, could predict the evolution of Usual Interstitial Pneumonia (UIP) towards a definite vasculitis in patients, with a better prognosis compared with IPF. In this view, ANCA testing should be included in the diagnostic workup of UIP patients.
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- 2023
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13. Anti-COVID-19 Potential of Ellagic Acid and Polyphenols of Punica granatum L.
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Ralitza Alexova, Simona Alexandrova, Stela Dragomanova, Reni Kalfin, Ayten Solak, Sidharth Mehan, Maria Cristina Petralia, Paolo Fagone, Katia Mangano, Ferdinando Nicoletti, and Lyubka Tancheva
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Punica granatum ,COVID-19 ,polyphenols ,ellagitannins ,ellagic acid ,Organic chemistry ,QD241-441 - Abstract
Pomegranate (Punica granatum L.) is a rich source of polyphenols, including ellagitannins and ellagic acid. The plant is used in traditional medicine, and its purified components can provide anti-inflammatory and antioxidant activity and support of host defenses during viral infection and recovery from disease. Current data show that pomegranate polyphenol extract and its ellagitannin components and metabolites exert their beneficial effects by controlling immune cell infiltration, regulating the cytokine secretion and reactive oxygen and nitrogen species production, and by modulating the activity of the NFκB pathway. In vitro, pomegranate extracts and ellagitannins interact with and inhibit the infectivity of a range of viruses, including SARS-CoV-2. In silico docking studies show that ellagitannins bind to several SARS-CoV-2 and human proteins, including a number of proteases. This warrants further exploration of polyphenol–viral and polyphenol–host interactions in in vitro and in vivo studies. Pomegranate extracts, ellagitannins and ellagic acid are promising agents to target the SARS-CoV-2 virus and to restrict the host inflammatory response to viral infections, as well as to supplement the depleted host antioxidant levels during the stage of recovery from COVID-19.
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- 2023
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14. Myositis-Specific and Myositis-Associated Antibodies in Fibromyalgia Patients: A Prospective Study
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Gianluca Sambataro, Martina Orlandi, Evelina Fagone, Mary Fruciano, Elisa Gili, Alessandro Libra, Stefano Palmucci, Carlo Vancheri, Lorenzo Malatino, Michele Colaci, and Domenico Sambataro
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fibromyalgia ,myositis-specific antibodies ,myositis-associated antibodies ,Sjögren’s syndrome ,antisynthetase syndrome ,idiopathic inflammatory myopathy ,Biology (General) ,QH301-705.5 - Abstract
Fibromyalgia (FM) is a common rheumatologic disorder characterised by widespread muscular pain. Myalgia is also a common clinical feature in Connective Tissue Disease (CTD), and FM should be studied for the concomitant presence of a CTD. The aim of this study is to evaluate the prevalence of Myositis-Specific and Myositis-Associated Antibodies (MSA/MAA) in a cohort of FM patients. We enrolled 233 consecutive FM patients (defined according to the 2016 criteria) that did not report clinical signs of autoimmune disorders and followed them for at least one year. The patients were tested for MSA/MAA with immunoblotting. FM patients were seropositive for Antinuclear Antibodies (ANA) in 24% of cases, for MSA in 9%, and for MAA in 6%. A specific diagnosis of CTD was made in 12 patients (5.2%), namely, 5 cases of primary Sjögren’s Syndrome and 7 of Idiopathic Inflammatory Myopathy. Seropositive patients showed clinical features similar to those who were seronegative at baseline. A CTD diagnosis was associated with ANA positivity (p = 0.03, X2 4.9), the presence of a speckled pattern (p = 0.02, X2 5.3), positivity for MAA (p = 0.004, X2 8.1), and MSA (p = 0.003, X2 9.2). In conclusion, a non-negligible proportion of FM patients may be seropositive for MSA/MAA, and that seropositivity might suggest a diagnosis of CTD.
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- 2023
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15. Preventive and Therapeutic Effects of Punica granatum L. Polyphenols in Neurological Conditions
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Simona Aleksandrova, Ralitza Alexova, Stela Dragomanova, Reni Kalfin, Ferdinando Nicoletti, Paolo Fagone, Maria Cristina Petralia, Katia Mangano, and Lyubka Tancheva
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pomegranate ,punicalagin ,ellagic acid ,mental health ,antioxidants ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Pomegranate (Punica granatum L.) is a polyphenol-rich food and medicinal plant containing flavonols, anthocyanins, and tannins. Ellagitannins (ETs) are the most abundant polyphenols in pomegranate. A growing body of research shows that polyphenol-rich pomegranate extracts and their metabolites target multiple types of brain cell and support their redox balance, proliferation and survival, as well as cell signaling. Independent studies have demonstrated that the significant neuroprotective effects of ETs are mediated by their antioxidant and anti-inflammatory effects, their chelating properties, by their ability to activate various signaling pathways, as well as the ability to influence mitochondrial damage, thus regulating autophagy, apoptosis and neurotransmitter signaling. The multitude of in vitro and in vivo studies summarized in the present review suggest that pomegranate polyphenols act on both neuronal and glial cells directly, and also affect blood–brain barrier function, restoring redox balance in the blood and brain and increasing blood flow to the brain.
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- 2023
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16. Gene Co-Expression Network Modular Analysis Reveals Altered Immune Mechanisms in HIV-HAND
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Maria Cristina Petralia, Ferdinando Nicoletti, Lyubka Tancheva, Reni Kalfin, Paolo Fagone, and Katia Mangano
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HIV ,HIV-HAND ,HIV-HAD ,HIVE neurocognitive impairment ,immune response ,National NeuroAIDS Tissue Consortium ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Although the introduction of HAART has completely changed the natural course of HIV infection, the number of chronic forms of HIV-associated neurocognitive disorder (HAND) has risen. It is estimated that up to half of subjects undergoing HAART therapy exhibit mild cognitive impairments. In the current study, we apply the gene co-expression network modular analysis, a well-established system biology approach, to the gene expression profiles of cases from the National NeuroAIDS Tissue Consortium (NNTC). We observed a negative enrichment for genes associated with the control of immune responses and putatively regulated by the transcription factors IRF8 and SPI1 and by both type I and II interferons. Our study provides evidence of altered immune responses, which are likely associated with the occurrence of HAND in the absence of HIV encephalitis (HIVE).
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- 2022
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17. Overexpression of Nudt7 decreases bile acid levels and peroxisomal fatty acid oxidation in the liver
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Stephanie A. Shumar, Evan W. Kerr, Paolo Fagone, Aniello M. Infante, and Roberta Leonardi
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beta-oxidation ,bile acid metabolism ,peroxisomes, metabolomics ,Nudix hydrolase 7 ,coenzyme A ,Biochemistry ,QD415-436 - Abstract
Lipid metabolism requires CoA, an essential cofactor found in multiple subcellular compartments, including the peroxisomes. In the liver, CoA levels are dynamically adjusted between the fed and fasted states. Elevated CoA levels in the fasted state are driven by increased synthesis; however, this also correlates with decreased expression of Nudix hydrolase (Nudt)7, the major CoA-degrading enzyme in the liver. Nudt7 resides in the peroxisomes, and we overexpressed this enzyme in mouse livers to determine its effect on the size and composition of the hepatic CoA pool in the fed and fasted states. Nudt7 overexpression did not change total CoA levels, but decreased the concentration of short-chain acyl-CoAs and choloyl-CoA in fasted livers, when endogenous Nudt7 activity was lowest. The effect on these acyl-CoAs correlated with a significant decrease in the hepatic bile acid content and in the rate of peroxisomal fatty acid oxidation, as estimated by targeted and untargeted metabolomics, combined with the measurement of fatty acid oxidation in intact hepatocytes. Identification of the CoA species and metabolic pathways affected by the overexpression on Nudt7 in vivo supports the conclusion that the nutritionally driven modulation of Nudt7 activity could contribute to the regulation of the peroxisomal CoA pool and peroxisomal lipid metabolism.
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- 2019
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18. Computational Analysis of Pathogenetic Pathways in Alzheimer’s Disease and Prediction of Potential Therapeutic Drugs
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Maria Cristina Petralia, Katia Mangano, Maria Catena Quattropani, Vittorio Lenzo, Ferdinando Nicoletti, and Paolo Fagone
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Alzheimer’s disease ,dementia ,therapeutic targets ,in silico pharmacology ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Background. Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disease which affects more than 50 million patients and represents 60–80% of all cases of dementia. Mutations in the APP gene, mostly affecting the γ-secretase site of cleavage and presenilin mutations, have been identified in inherited forms of AD. Methods. In the present study, we performed a meta-analysis of the transcriptional signatures that characterize two familial AD mutations (APPV7171F and PSEN1M146V) in order to characterize the common altered biomolecular pathways affected by these mutations. Next, an anti-signature perturbation analysis was performed using the AD meta-signature and the drug meta-signatures obtained from the L1000 database, using cosine similarity as distance metrics. Results. Overall, the meta-analysis identified 1479 differentially expressed genes (DEGs), 684 downregulated genes, and 795 upregulated genes. Additionally, we found 14 drugs with a significant anti-similarity to the AD signature, with the top five drugs being naftifine, moricizine, ketoconazole, perindopril, and fexofenadine. Conclusions. This study aimed to integrate the transcriptional profiles associated with common familial AD mutations in neurons in order to characterize the pathogenetic mechanisms involved in AD and to find more effective drugs for AD.
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- 2022
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19. Navigated Transcranial Magnetic Stimulation Motor Mapping Usefulness in the Surgical Management of Patients Affected by Brain Tumors in Eloquent Areas: A Systematic Review and Meta-Analysis
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Giuseppe Emmanuele Umana, Gianluca Scalia, Francesca Graziano, Rosario Maugeri, Nicola Alberio, Fabio Barone, Antonio Crea, Saverio Fagone, Giuseppe Roberto Giammalva, Lara Brunasso, Roberta Costanzo, Federica Paolini, Rosa Maria Gerardi, Silvana Tumbiolo, Salvatore Cicero, Giovanni Federico Nicoletti, and Domenico Gerardo Iacopino
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NTMs ,motor mapping ,surgical planning ,glioma ,craniotomy ,tractography ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: The surgical strategy for brain glioma has changed, shifting from tumor debulking to a more careful tumor dissection with the aim of a gross-total resection, extended beyond the contrast-enhancement MRI, including the hyperintensity on FLAIR MR images and defined as supratotal resection. It is possible to pursue this goal thanks to the refinement of several technological tools for pre and intraoperative planning including intraoperative neurophysiological monitoring (IONM), cortico-subcortical mapping, functional MRI (fMRI), navigated transcranial magnetic stimulation (nTMS), intraoperative CT or MRI (iCT, iMR), and intraoperative contrast-enhanced ultrasound. This systematic review provides an overview of the state of the art techniques in the application of nTMS and nTMS-based DTI-FT during brain tumor surgery.Materials and Methods: A systematic literature review was performed according to the PRISMA statement. The authors searched the PubMed and Scopus databases until July 2020 for published articles with the following Mesh terms: (Brain surgery OR surgery OR craniotomy) AND (brain mapping OR functional planning) AND (TMS OR transcranial magnetic stimulation OR rTMS OR repetitive transcranial stimulation). We only included studies regarding motor mapping in craniotomy for brain tumors, which reported data about CTS sparing.Results: A total of 335 published studies were identified through the PubMed and Scopus databases. After a detailed examination of these studies, 325 were excluded from our review because of a lack of data object in this search. TMS reported an accuracy range of 0.4–14.8 mm between the APB hotspot (n1/4 8) in nTMS and DES from the DES spot; nTMS influenced the surgical indications in 34.3–68.5%.Conclusion: We found that nTMS can be defined as a safe and non-invasive technique and in association with DES, fMRI, and IONM, improves brain mapping and the extent of resection favoring a better postoperative outcome.
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- 2021
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20. Reciprocal Interplay Between Astrocytes and CD4+ Cells Affects Blood-Brain Barrier and Neuronal Function in Response to β Amyloid
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Simona Federica Spampinato, Sara Merlo, Evelina Fagone, Mary Fruciano, Yasuteru Sano, Takashi Kanda, and Maria Angela Sortino
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BBB ,Th2 ,IL-4 ,BDNF ,synaptophysin ,neurodegeneration ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Background: In Alzheimer’s disease (AD) neuronal degeneration is associated with gliosis and infiltration of peripheral blood mononuclear cells (PBMCs), which participate in neuroinflammation. Defects at the blood-brain barrier (BBB) facilitate PBMCs migration towards the central nervous system (CNS) and in particular CD4+ T cells have been found in areas severely affected in AD. However, the role of T cells, once they migrate into the CNS, is not well defined. CD4+ cells interact with astrocytes able to release several factors and cytokines that can modulate T cell polarization; similarly, astrocytic properties are modulated after interaction with T cells.Methods: In in vitro models, astrocytes were primed with β-amyloid (Aβ; 2.5 μM, 5 h) and then co-cultured with magnetically isolated CD4+ cells. Cytokines expression was evaluated both in co-cultured CD4+ cells and astrocytes. The effects of this crosstalk were further evaluated by co-culturing CD4+ cells with the neuronal-like SH-SY5Y cell line and astrocytes with endothelial cells.Results: The pattern of cytokines and trophic factors expressed by CD4+ cells were strongly modulated in the presence of Aβ-primed astrocytes. Specifically, the percentage of IL-4+ and IFNγ+ CD4+ cells was significantly increased and reduced, respectively. Further, increased BDNF mRNA levels were observed in CD4+ cells. When SH-SY5Y cells were co-cultured with astrocyte-conditioned CD4+ cells and exposed to Aβ, the reduction of the presynaptic protein synaptophysin was prevented with a BDNF-dependent mechanism. In astrocytes co-cultured with CD4+ cells, reduced mRNA levels of inflammatory cytokines and VEGF were observed. This was paralleled by the prevention of the reduction of claudin-5 when astrocytes were co-cultured with endothelial cells.Conclusion: Following Aβ exposure, there exists reciprocal crosstalk between infiltrating peripheral cells and astrocytes that in turn affects not only endothelial function and thus BBB properties, but also neuronal behavior. Since astrocytes are the first cells that lymphocytes interact with and are among the principal players in neuroinflammation occurring in AD, understanding this crosstalk may disclose new potential targets of intervention in the treatment of neurodegeneration.
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- 2020
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21. Giant cystic brain metastasis from ovarian papillary serous adenocarcinoma: Case report and review of the literature
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Giuseppe Emmanuele Umana, Nicola Alberio, Paolo Amico, Anna Maria Lavecchia, Saverio Fagone, Marco Fricia, Giovanni Nicoletti, Salvatore Cicero, and Gianluca Scalia
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Surgery ,RD1-811 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Ovarian brain metastases represent a very rare occurrence and without treatment, prognosis is very poor, with a median survival of one month. We present a unique case of a patient affected by a giant cystic intracerebral metastasis (>7 cm) secondary to an ovarian papillary serous adenocarcinoma, along with a review of the literature regarding large cystic ovarian metastases and their management. Case description: A 49-years-old female patient was admitted to our institution because she presented progressive headache and altered consciousness. Brain computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed the presence of a giant left frontal intracerebral cystic lesion. The patient underwent a surgical removal of an ovarian high-grade papillary serous adenocarcinoma three years before. We performed a left frontal craniotomy and microsurgical removal of the brain lesion, achieving a safe macroscopic total resection, thanks to intraoperative neurophysiological monitoring (IONM). The post-operative period was uneventful with a complete recovery. Post-operative brain MRI showed a complete removal of the lesion. Conclusions: The presence of a giant cystic metastasis with symptoms of intracranial hypertension needs a radical and safe surgical removal, along with the management of a multidisciplinary oncologic group. Keywords: Brain metastasis, Ovarian carcinoma, Cystic, Giant
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- 2020
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22. Modeling of the Tensile Behavior FRCM Systems for Repair and Strengthening Interventions of Masonry Structures
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Ernesto Grande, Gabriele Milani, Elisa Bertolesi, Mario Fagone, and Tommaso Rotunno
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FRCM ,tensile test ,cracking ,de-bonding ,modeling ,Engineering (General). Civil engineering (General) ,TA1-2040 ,City planning ,HT165.5-169.9 - Abstract
Fiber Reinforced Cementitious Matrix (FRCM) systems are an innovative solution for strengthening interventions of existing masonry and concrete constructions. The current literature provides interesting experimental and numerical studies which underline the potentialities of FRCMs and their specific features. Direct tensile tests are generally used for characterizing the behavior of FRCM strengthening systems. These tests particularly underline the occurrence of both matrix cracking and debonding of the reinforcement from the matrix, phenomena which particularly influence the performance of FRCM systems. The present paper aims at numerically analyzing the response of FRCM strengthening systems during tensile tests carried out throughout different setup configurations. To this end, a simple model carried out from literature and opportunely modified is presented in the paper and validated with reference to experimental case studies. Moreover, the obtained results are critically examined to emphasize the role of the proposed model for the interpretation of the results carried out from standard tensile tests.
- Published
- 2020
- Full Text
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23. Immunobiology of Uveal Melanoma: State of the Art and Therapeutic Targets
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Maria Sofia Basile, Emanuela Mazzon, Paolo Fagone, Antonio Longo, Andrea Russo, Matteo Fallico, Vincenza Bonfiglio, Ferdinando Nicoletti, Teresio Avitabile, and Michele Reibaldi
- Subjects
uveal melanoma ,inhibitory checkpoints ,immunotherapy ,immune-escape ,immune-privilege ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Uveal Melanoma (UM) represents the most common primary intraocular malignant tumor in adults. Although it originates from melanocytes as cutaneous melanoma, it shows significant clinical and biological differences with the latter, including high resistance to immune therapy. Indeed, UM can evade immune surveillance via multiple mechanisms, such as the expression of inhibitory checkpoints (e.g., PD-L1, CD47, CD200) and the production of IDO-1 and soluble FasL, among others. More in-depth understanding of these mechanisms will suggest potential targets for the design of novel and more effective management strategies for UM patients.
- Published
- 2019
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- View/download PDF
24. Therapeutic Potential of Alpha-Lipoic Acid in Viral Infections, including COVID-19
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Stela Dragomanova, Simona Miteva, Ferdinando Nicoletti, Katia Mangano, Paolo Fagone, Salvatore Pricoco, Hristian Staykov, and Lyubka Tancheva
- Subjects
alfa-lipoic acid ,antioxidants ,natural products ,oxidative responses ,viral infections ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Oxidative stress (OS), resulting from a disrupted balance between reactive oxygen species (ROS) and protective antioxidants, is thought to play an important pathogenetic role in several diseases, including viral infections. Alpha-lipoic acid (LA) is one of the most-studied and used natural compounds, as it is endowed with a well-defined antioxidant and immunomodulatory profile. Owing to these properties, LA has been tested in several chronic immunoinflammatory conditions, such as diabetic neuropathy and metabolic syndrome. In addition, a pharmacological antiviral profile of LA is emerging, that has attracted attention on the possible use of this compound for the cotreatment of several viral infections. Here, we will review the emerging literature on the potential use of LA in viral infections, including COVID-19.
- Published
- 2021
- Full Text
- View/download PDF
25. Transcriptomic Data Analysis Reveals a Down-Expression of Galectin-8 in Schizophrenia Hippocampus
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Maria Cristina Petralia, Rosella Ciurleo, Alessia Bramanti, Placido Bramanti, Andrea Saraceno, Katia Mangano, Maria Catena Quattropani, Ferdinando Nicoletti, and Paolo Fagone
- Subjects
schizophrenia ,hippocampus ,galectins ,LGALS8 ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Schizophrenia (SCZ) is a severe psychiatric disorder with several clinical manifestations that include cognitive dysfunction, decline in motivation, and psychosis. Current standards of care treatment with antipsychotic agents are often ineffective in controlling the disease, as only one-third of SCZ patients respond to medications. The mechanisms underlying the pathogenesis of SCZ remain elusive. It is believed that inflammatory processes may play a role as contributing factors to the etiology of SCZ. Galectins are a family of β-galactoside-binding lectins that contribute to the regulation of immune and inflammatory responses, and previous reports have shown their role in the maintenance of central nervous system (CNS) homeostasis and neuroinflammation. In the current study, we evaluated the expression levels of the galectin gene family in post-mortem samples of the hippocampus, associative striatum, and dorsolateral prefrontal cortex from SCZ patients. We found a significant downregulation of LGALS8 (Galectin-8) in the hippocampus of SCZ patients as compared to otherwise healthy donors. Interestingly, the reduction of LGALS8 was disease-specific, as no modulation was observed in the hippocampus from bipolar nor major depressive disorder (MDD) patients. Prediction analysis identified TBL1XR1, BRF2, and TAF7 as potential transcription factors controlling LGALS8 expression. In addition, MIR3681HG and MIR4296 were negatively correlated with LGALS8 expression, suggesting a role for epigenetics in the regulation of LGALS8 levels. On the other hand, no differences in the methylation levels of LGALS8 were observed between SCZ and matched control hippocampus. Finally, ontology analysis of the genes negatively correlated with LGALS8 expression identified an enrichment of the NGF-stimulated transcription pathway and of the oligodendrocyte differentiation pathway. Our study identified LGALS8 as a disease-specific gene, characterizing SCZ patients, that may in the future be exploited as a potential therapeutic target.
- Published
- 2021
- Full Text
- View/download PDF
26. Differential modulation and prognostic values of immune-escape genes in uveal melanoma.
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Maria Sofia Basile, Emanuela Mazzon, Andrea Russo, Santa Mammana, Antonio Longo, Vincenza Bonfiglio, Matteo Fallico, Rosario Caltabiano, Paolo Fagone, Ferdinando Nicoletti, Teresio Avitabile, and Michele Reibaldi
- Subjects
Medicine ,Science - Abstract
Uveal melanoma (UM) is the most common primary intraocular cancer in adults. In the present study, we aimed to characterize the immunological features of primary UM cancer and to provide an association with prognostic markers and outcome. Also, we assessed the influence of the microenvironment on the expression of inhibitory immune checkpoints in UM. Genes of interest included MHC Class I and Class II molecules, as well as inhibitory immune-checkpoints, i.e. PDL1, PDL2, B7-H3, B7-H4, TBFRSF6B, CD47, CD155, GAL9, HVEM and CD200. We observed significant lower levels of MHC genes in UM cells as compared to normal uveal melanocytes. Unexpectedly however, the expression levels of most of the analyzed inhibitory immune-checkpoint genes were not different in cancer cells as compared to normal melanocytes, with the exception of CD200 and HVEM, that resulted significantly reduced. On the other hand, PDL1 inversely correlated with OS, PFS and thickness of the tumor. Also, PDL1, along with PDL2, expression significantly increased under inflammatory conditions. Finally, for the first time, we propose a possible role for CD47 in the immune evasive properties of UM. We show here that CD47 is significantly upregulated by UM cells following inflammatory stimuli and that it represents a good independent predictor of disease progression. The results from this study may propel advances in the development of immune-based therapies for UM patients.
- Published
- 2019
- Full Text
- View/download PDF
27. Macrophage Migration Inhibitory Factor (MIF) and Its Homologue D-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus
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Rosario Caltabiano, Rocco De Pasquale, Eliana Piombino, Giorgia Campo, Ferdinando Nicoletti, Eugenio Cavalli, Katia Mangano, and Paolo Fagone
- Subjects
discoid lupus erythematosus ,macrophage migration inhibitory factor ,d-dopachrome tautomerase ,Organic chemistry ,QD241-441 - Abstract
Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.
- Published
- 2021
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- View/download PDF
28. Cognitive Decline in Rheumatoid Arthritis: Insight into the Molecular Pathogenetic Mechanisms
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Maria Sofia Basile, Rosella Ciurleo, Alessia Bramanti, Maria Cristina Petralia, Paolo Fagone, Ferdinando Nicoletti, and Eugenio Cavalli
- Subjects
rheumatoid arthritis ,cognitive decline ,pathogenesis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Cognitive decline refers to a deterioration of intellectual and learning abilities and related memory problems, and is often associated with behavioral alterations, which prevents sufferers from carrying out the most common daily activities, such as maintaining normal productive interpersonal relationships, communicating, and leading an autonomous life. Numerous studies have highlighted the association between cognitive decline and autoimmune disorders, including rheumatoid arthritis (RA). RA is a chronic, inflammatory, autoimmune disease that involves systems and organs other than the bones and joints, with varying severity among patients. Here, we review the studies investigating the link between cognitive decline and RA, focusing on the main molecular pathogenetic mechanisms involved. The emerging body of data suggests that clinical, psychological, and biological factors may contribute to the pathogenesis of cognitive decline in RA, including cardiovascular complications, chronic pain, depression, inflammatory factors, changes in hormone levels, drug side effects, and genetics. Further studies are warranted in order to fully clarify the basis underlying the association between cognitive decline and RA and to find new possible diagnostic strategies and therapeutic targets for RA patients.
- Published
- 2021
- Full Text
- View/download PDF
29. Soil contaminated with PAHs and nitro-PAHs: contamination levels in an urban area of Catania (Sicily, southern Italy) and experimental results from simulated decontamination treatment
- Author
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De Guidi, Guido, Falciglia, Pietro P., Catalfo, Alfio, De Guidi, Giorgio, Fagone, Sonia, and Vagliasindi, Federico G. A.
- Published
- 2017
- Full Text
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30. Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis
- Author
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Antonio Pesce, Rosella Ciurleo, Alessia Bramanti, Eliana Concetta Armeli Iapichino, Maria Cristina Petralia, Gaetano Giuseppe Magro, Paolo Fagone, Placido Bramanti, Ferdinando Nicoletti, and Katia Mangano
- Subjects
liver fibrosis ,imatinib ,sorafenib ,traumatic spinal cord injury ,Organic chemistry ,QD241-441 - Abstract
Liver fibrosis is defined as excessive extracellular matrix deposition in the hepatic parenchyma as a consequence of complex interactions among matrix-producing hepatic stellate cells (HSCs) and liver-resident and infiltrating cells. In addition to the liver, the process of fibrosis may represent end-stage disease of several diseases including kidneys, lungs, spleens, heart, muscles and at certain extent, the central nervous system and the peripheral nerves. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development. The aim of the present study was to test the efficacy of a new drug combination for the treatment of hepatic fibrosis in order to provide a proof-of-concept for the use of therapeutic agents in clinical practice. For this purpose, we have studied the effects of the PDGF inhibitor imatinib and the angiogenesis inhibitor sorafenib, administered alone or in combination, in reducing the progression of the fibrogenetic process in a pre-clinical model of liver damage induced in mice by repeated administration of Concanavalin A (ConA), resembling long-tern autoimmune hepatitis. Our results suggest that treatments with imatinib and sorafenib can modulate potently and, in a superimposable fashion, the fibrinogenic process when administered alone. However, and in agreement with the computational data presently generated, they only exert partial overlapping antifibrotic effects in modulating the main pathways involved in the process of liver fibrosis, without significant additive or synergist effects, when administered in combination.
- Published
- 2020
- Full Text
- View/download PDF
31. Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis
- Author
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Milica Lazarević, Giuseppe Battaglia, Bojan Jevtić, Neda Djedovic, Valeria Bruno, Eugenio Cavalli, Đorđe Miljković, Ferdinando Nicoletti, Miljana Momčilović, and Paolo Fagone
- Subjects
carbon monoxide ,dendritic cells ,experimental autoimmune encephalomyelitis ,hydrogen sulfide ,multiple sclerosis ,nitric oxide ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The aim of this study was to examine the in vitro effects of the slow-releasing H2S donor GYY4137 on the immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-β expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17+ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, the peripheral blood mononuclear cells obtained from the MS patients had a lower expression of the H2S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted.
- Published
- 2020
- Full Text
- View/download PDF
32. The Dichotomic Role of Macrophage Migration Inhibitory Factor in Neurodegeneration
- Author
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Maria Sofia Basile, Giuseppe Battaglia, Valeria Bruno, Katia Mangano, Paolo Fagone, Maria Cristina Petralia, Ferdinando Nicoletti, and Eugenio Cavalli
- Subjects
macrophage migration inhibitory factor ,neurodegeneration ,amyotrophic lateral sclerosis ,Parkinson disease ,Huntington disease ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine expressed by different cell types and exerting multiple biological functions. It has been shown that MIF may be involved in several disorders, including neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Parkinson disease (PD), and Huntington disease (HD), that represent an unmet medical need. Therefore, further studies are needed to identify novel pathogenetic mechanisms that may translate into tailored therapeutic approaches so to improve patients’ survival and quality of life. Here, we reviewed the preclinical and clinical studies investigating the role of MIF in ALS, PD, and HD. The emerging results suggest that MIF might play a dichotomic role in these disorders, exerting a protective action in ALS, a pathogenetic action in HD, and a yet undefined and debated role in PD. The better understanding of the role of MIF in these diseases could allow its use as a novel diagnostic and therapeutic tool for the monitoring and treatment of the patients and for eventual biomarker-driven therapeutic approaches.
- Published
- 2020
- Full Text
- View/download PDF
33. Nailfold Videocapillaroscopy Is a Useful Tool to Recognize Definite Forms of Systemic Sclerosis and Idiopathic Inflammatory Myositis in Interstitial Lung Disease Patients
- Author
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Domenico Sambataro, Gianluca Sambataro, Alessandro Libra, Giovanna Vignigni, Fabio Pino, Evelina Fagone, Mary Fruciano, Elisa Gili, Francesca Pignataro, Nicoletta Del Papa, and Carlo Vancheri
- Subjects
nailfold videocapillaroscopy ,multidisciplinary team ,interstitial lung disease ,idiopathic pulmonary fibrosis ,interstitial pneumonia with autoimmune features ,systemic sclerosis ,Medicine (General) ,R5-920 - Abstract
Nailfold videocapillaroscopy (NVC) is an easy tool used for the assessment of patients with Raynaud’s phenomenon (RP) as possibly associated with systemic sclerosis (SSc). Recent insights have also highlighted its role in the diagnostic assessment of idiopathic inflammatory myopathies (IIMs). The aim of this study is to describe the diagnostic role of NVC in a series of 361 consecutive patients with interstitial lung disease (ILD). All the patients were assessed by clinical pulmonary and rheumatic examinations, blood exams, high-resolution computed tomography and NVC. NVC was considered positive only in the presence of avascular areas or giant capillaries, but also, the presence of bushy capillaries (BCs) was recorded. NVC was positive in 17.7% of ILD patients and in 78.1% of ILD patients associated with a diagnosis of connective tissue disease (CTD). In 25% of SSc-ILD patients, NVC proved necessary for a correct diagnosis. The presence of BCs and/or NVC positivity in ILD patients with normal levels of creatine phosphokinase is associated with amyopathic IIM, regardless the presence of RP. In conclusion, NVC is useful for the diagnostic assessment of incomplete forms of CTD and in amyopathic IIMs. NVC should be considered in the diagnostic assessment of ILD patients regardless of the presence of RP.
- Published
- 2020
- Full Text
- View/download PDF
34. Patients with Interstitial Lung Disease Secondary to Autoimmune Diseases: How to Recognize Them?
- Author
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Domenico Sambataro, Gianluca Sambataro, Francesca Pignataro, Giovanni Zanframundo, Veronica Codullo, Evelina Fagone, Emanuele Martorana, Francesco Ferro, Martina Orlandi, Nicoletta Del Papa, Lorenzo Cavagna, Lorenzo Malatino, Michele Colaci, and Carlo Vancheri
- Subjects
interstitial lung disease ,idiopathic pulmonary fibrosis ,interstitial pneumonia with autoimmune features ,systemic sclerosis ,myositis ,antisynthetase syndrome ,Medicine (General) ,R5-920 - Abstract
The diagnostic assessment of patients with Interstitial Lung Disease (ILD) can be challenging due to the large number of possible causes. Moreover, the diagnostic approach can be limited by the severity of the disease, which may not allow invasive exams. To overcome this issue, the referral centers for ILD organized Multidisciplinary Teams (MDTs), including physicians and experts in complementary discipline, to discuss the management of doubtful cases of ILD. MDT is currently considered the gold standard for ILD diagnosis, but it is not often simple to organize and, furthermore, rheumatologists are still not always included. In fact, even if rheumatologic conditions represent a common cause of ILD, they are sometimes difficult to recognize, considering the variegated clinical features and their association with all possible radiographic patterns of ILD. The first objective of this review is to describe the clinical, laboratory, and instrumental tests that can drive a diagnosis toward a possible rheumatic disease. The secondary objective is to propose a set of first-line tests to perform in all patients in order to recognize any possible rheumatic conditions underlying ILD.
- Published
- 2020
- Full Text
- View/download PDF
35. Vitamin D3 inhibits TNFα-induced latent HIV reactivation in J-LAT cells
- Author
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Nunnari, G., Fagone, P., Lazzara, F., Longo, A., Cambria, D., Di Stefano, G., Palumbo, M., Malaguarnera, L., and Di Rosa, Michelino
- Published
- 2016
- Full Text
- View/download PDF
36. Characterization of the Pathophysiological Role of CD47 in Uveal Melanoma
- Author
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Maria Cristina Petralia, Emanuela Mazzon, Paolo Fagone, Andrea Russo, Antonio Longo, Teresio Avitabile, Ferdinando Nicoletti, Michele Reibaldi, and Maria Sofia Basile
- Subjects
uveal melanoma ,immune checkpoints ,immunotherapy ,CD47 ,Organic chemistry ,QD241-441 - Abstract
Uveal melanoma (UM) represents the most frequent primary intraocular tumor, however, limited therapeutic options are still available. We have previously shown that cluster of differentiation 47 (CD47) is significantly upregulated in UM cells following inflammatory stimuli and that it represents a predictor of disease progression. Here, we aimed to better characterize the pathophysiological role of CD47 in UM. We show that CD47 is not modulated at different cancer stages, although patients with the lowest expression of CD47 show significant better progression-free survival, after correcting for the presence of BAP1, GNAQ, and GNA11 mutations. By stratifying patients based on the expression of CD47 in the tumor, we observed that patients with high levels of CD47 have a significant increase in immune score as compared to patients with low levels of CD47. In particular, deconvolution analysis of infiltrating immune cell populations revealed that a significantly higher number of CD4+ and CD8+ T cells can be found in patients with high CD47 levels, with the most enriched populations being the Th2, Treg, and CD8+ Tcm cells. We also show that a large number of transcripts are significantly modulated between the groups of patients with high and low levels of CD47, with a significant enrichment of interferon IFN-alpha regulated genes. The results from this study may propel the development of anti-CD47 therapies for UM patients.
- Published
- 2019
- Full Text
- View/download PDF
37. Identification of novel chemotherapeutic strategies for metastatic uveal melanoma
- Author
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Fagone, Paolo, Caltabiano, Rosario, Russo, Andrea, Lupo, Gabriella, Anfuso, Carmelina Daniela, Basile, Maria Sofia, Longo, Antonio, Nicoletti, Ferdinando, De Pasquale, Rocco, Libra, Massimo, and Reibaldi, Michele
- Published
- 2017
- Full Text
- View/download PDF
38. CD4+ T-cell gene expression of healthy donors, HIV-1 and elite controllers: Immunological chaos
- Author
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Nunnari, G., Fagone, P., Condorelli, F., Nicoletti, F., Malaguarnera, L., and Di Rosa, M.
- Published
- 2016
- Full Text
- View/download PDF
39. Induction of OAS gene family in HIV monocyte infected patients with high and low viral load
- Author
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Fagone, P., Nunnari, G., Lazzara, F., Longo, A., Cambria, D., Distefano, G., Palumbo, M., Nicoletti, F., Malaguarnera, L., and Di Rosa, M.
- Published
- 2016
- Full Text
- View/download PDF
40. Modulation of heat shock proteins during macrophage differentiation
- Author
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Fagone, Paolo, Di Rosa, Michelino, Palumbo, Maria, De Gregorio, Corinne, Nicoletti, Ferdinando, and Malaguarnera, Lucia
- Published
- 2012
- Full Text
- View/download PDF
41. Molecular adjuvant HMGB1 enhances anti-influenza immunity during DNA vaccination
- Author
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Fagone, P, Shedlock, D J, Bao, H, Kawalekar, O U, Yan, J, Gupta, D, Morrow, M P, Patel, A, Kobinger, G P, Muthumani, K, and Weiner, D B
- Published
- 2011
- Full Text
- View/download PDF
42. Targeting the translational apparatus to improve leukemia therapy: roles of the PI3K/PTEN/Akt/mTOR pathway
- Author
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Martelli, A M, Evangelisti, C, Chappell, W, Abrams, S L, Bäsecke, J, Stivala, F, Donia, M, Fagone, P, Nicoletti, F, Libra, M, Ruvolo, V, Ruvolo, P, Kempf, C R, Steelman, L S, and McCubrey, J A
- Published
- 2011
- Full Text
- View/download PDF
43. Roles of the Ras/Raf/MEK/ERK pathway in leukemia therapy
- Author
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Steelman, L S, Franklin, R A, Abrams, S L, Chappell, W, Kempf, C R, Bäsecke, J, Stivala, F, Donia, M, Fagone, P, Nicoletti, F, Libra, M, Ruvolo, P, Ruvolo, V, Evangelisti, C, Martelli, A M, and McCubrey, J A
- Published
- 2011
- Full Text
- View/download PDF
44. Curved masonry supports strengthened with TRM materials: Advanced Fe modelling
- Author
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Grande, E., Bertolesi, E., Milani, G., Rotunno, T., and Fagone, M.
- Published
- 2022
- Full Text
- View/download PDF
45. Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat
- Author
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Celasco, Giuseppe, Moro, Luigi, Bozzella, Roberta, Mangano, Katia, Quattrocchi, Cinzia, Aiello, Caterina, Donia, Marco, Fagone, Paolo, and Di Marco, Roberto
- Published
- 2008
- Full Text
- View/download PDF
46. A DNA vaccine against chikungunya virus is protective in mice and induces neutralizing antibodies in mice and nonhuman primates.
- Author
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Karthik Mallilankaraman, Devon J Shedlock, Huihui Bao, Omkar U Kawalekar, Paolo Fagone, Aarthi A Ramanathan, Bernadette Ferraro, Jennifer Stabenow, Paluru Vijayachari, Senthil G Sundaram, Nagarajan Muruganandam, Gopalsamy Sarangan, Padma Srikanth, Amir S Khan, Mark G Lewis, J Joseph Kim, Niranjan Y Sardesai, Karuppiah Muthumani, and David B Weiner
- Subjects
Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus indigenous to tropical Africa and Asia. Acute illness is characterized by fever, arthralgias, conjunctivitis, rash, and sometimes arthritis. Relatively little is known about the antigenic targets for immunity, and no licensed vaccines or therapeutics are currently available for the pathogen. While the Aedes aegypti mosquito is its primary vector, recent evidence suggests that other carriers can transmit CHIKV thus raising concerns about its spread outside of natural endemic areas to new countries including the U.S. and Europe. Considering the potential for pandemic spread, understanding the development of immunity is paramount to the development of effective counter measures against CHIKV. In this study, we isolated a new CHIKV virus from an acutely infected human patient and developed a defined viral challenge stock in mice that allowed us to study viral pathogenesis and develop a viral neutralization assay. We then constructed a synthetic DNA vaccine delivered by in vivo electroporation (EP) that expresses a component of the CHIKV envelope glycoprotein and used this model to evaluate its efficacy. Vaccination induced robust antigen-specific cellular and humoral immune responses, which individually were capable of providing protection against CHIKV challenge in mice. Furthermore, vaccine studies in rhesus macaques demonstrated induction of nAb responses, which mimicked those induced in convalescent human patient sera. These data suggest a protective role for nAb against CHIKV disease and support further study of envelope-based CHIKV DNA vaccines.
- Published
- 2011
- Full Text
- View/download PDF
47. Reactive oxygen species are required for maintenance and differentiation of primary lung fibroblasts in idiopathic pulmonary fibrosis.
- Author
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Marialuisa Bocchino, Savina Agnese, Evelina Fagone, Silvia Svegliati, Domenico Grieco, Carlo Vancheri, Armando Gabrielli, Alessandro Sanduzzi, and Enrico V Avvedimento
- Subjects
Medicine ,Science - Abstract
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal illness whose pathogenesis remains poorly understood. Recent evidence suggests oxidative stress as a key player in the establishment/progression of lung fibrosis in animal models and possibly in human IPF. The aim of the present study was to characterize the cellular phenotype of fibroblasts derived from IPF patients and identify underlying molecular mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We first analyzed the baseline differentiation features and growth ability of primary lung fibroblasts derived from 7 histology proven IPF patients and 4 control subjects at different culture passages. Then, we focused on the redox state and related molecular pathways of IPF fibroblasts and investigated the impact of oxidative stress in the establishment of the IPF phenotype. IPF fibroblasts were differentiated into alpha-smooth muscle actin (SMA)-positive myofibroblasts, displayed a pro-fibrotic phenotype as expressing type-I collagen, and proliferated lower than controls cells. The IPF phenotype was inducible upon oxidative stress in control cells and was sensitive to ROS scavenging. IPF fibroblasts also contained large excess of reactive oxygen species (ROS) due to the activation of an NADPH oxidase-like system, displayed higher levels of tyrosine phosphorylated proteins and were more resistant to oxidative-stress induced cell death. Interestingly, the IPF traits disappeared with time in culture, indicating a transient effect of the initial trigger. CONCLUSIONS/SIGNIFICANCE: Robust expression of α-SMA and type-I collagen, high and uniformly-distributed ROS levels, resistance to oxidative-stress induced cell death and constitutive activation of tyrosine kinase(s) signalling are distinctive features of the IPF phenotype. We suggest that this phenotype can be used as a model to identify the initial trigger of IPF.
- Published
- 2010
- Full Text
- View/download PDF
48. Membrane phospholipid synthesis and endoplasmic reticulum function
- Author
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Paolo Fagone and Suzanne Jackowski
- Subjects
phospholipids ,sphingolipids ,plasmalogens ,unfolded protein response ,Biochemistry ,QD415-436 - Abstract
This review presents an overview of mammalian phospholipid synthesis and the cellular locations of the biochemical activities that produce membrane lipid molecular species. The generalized endoplasmic reticulum compartment is a central site for membrane lipid biogenesis, and examples of the emerging relationships between alterations in lipid composition, regulation of membrane lipid biogenesis, and cellular secretory function are discussed.
- Published
- 2009
- Full Text
- View/download PDF
49. The immunobiology of apotransferrin in type 1 diabetes
- Author
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Mangano, K., Fagone, P., Di Mauro, M., Ascione, E., Maiello, V., Milicic, T., Jotic, A., Lalic, N. M., Saksida, T., Stojanovic, I., Selmi, C., Farina, C., Stosic-Grujicic, S., Meroni, P., and Nicoletti, F.
- Published
- 2012
- Full Text
- View/download PDF
50. Therapeutic potential of carbon monoxide in multiple sclerosis
- Author
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Fagone, P., Mangano, K., Coco, M., Perciavalle, V., Garotta, G., Romao, C. C., and Nicoletti, F.
- Published
- 2012
- Full Text
- View/download PDF
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