34 results on '"Mazzoni, Mr"'
Search Results
2. Putative Biomarkers for Malignant Pleural Mesothelioma Suggested by Proteomic Analysis of Cell Secretome.
- Author
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Lacerenza, S, Ciregia, F, Giusti, L, Bonotti, A, Greco, Viviana, Giannaccini, G, D'Antongiovanni, V, Fallahi, P, Pieroni, L, Cristaudo, A, Lucacchini, A, Mazzoni, Mr, Foddis, R, Greco V (ORCID:0000-0003-4521-0020), Lacerenza, S, Ciregia, F, Giusti, L, Bonotti, A, Greco, Viviana, Giannaccini, G, D'Antongiovanni, V, Fallahi, P, Pieroni, L, Cristaudo, A, Lucacchini, A, Mazzoni, Mr, Foddis, R, and Greco V (ORCID:0000-0003-4521-0020)
- Abstract
BACKGROUND:Malignant pleural mesothelioma (MPM) a rare neoplasm linked to asbestos exposure is characterized by a poor prognosis. Soluble mesothelin is currently considered the most specific diagnostic biomarker. The aim of the study was to identify novel biomarkers by proteomic analysis of two MPM cell lines secretome. MATERIALS AND METHODS:The protein patterns of MPM cells secretome were examined and compared to a non-malignant mesothelial cell line using two-dimensional gel electrophoresis coupled to mass spectrometry. Serum levels of candidate biomarkers were determined in MPM patients and control subjects. RESULTS:Two up-regulated proteins involved in cancer biology, prosaposin and quiescin Q6 sulfhydryl oxidase 1, were considered candidate biomarkers. Serum levels of both proteins were significantly higher in MPM patients than control subjects. Combining the data of each receiver-operating characteristic analysis predicted a good diagnostic accuracy. CONCLUSION:A panel of the putative biomarkers represents a promising tool for MPM diagnosis.
- Published
- 2020
3. Putative salivary biomarkers useful to differentiate patients with fibromyalgia
- Author
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Ciregia, F, Giacomelli, C, Giusti, L, Boldrini, C, Piga, I, Pepe, P, Consensi, A, Gori, S, Lucacchini, A, Mazzoni, M, Bazzichi, L, Mazzoni, MR, Ciregia, F, Giacomelli, C, Giusti, L, Boldrini, C, Piga, I, Pepe, P, Consensi, A, Gori, S, Lucacchini, A, Mazzoni, M, Bazzichi, L, and Mazzoni, MR
- Abstract
Fibromyalgia (FM) is a chronic pain disorder characterized by widespread pain and associated with unspecific symptoms. So far, no laboratory tests have been validated. The aim of the present study was to investigate the presence in saliva of potential diagnostic and/or prognostic biomarkers which could be useful for the management of FM patients. Specifically, the salivary profile of FM patients was compared with those of healthy subjects, subjects suffering migraine (model of non-inflammatory chronic pain), and patients affected by rheumatoid arthritis (model of inflammatory chronic pain). For proteomics analysis 2-DE and SELDI-TOF-MS were applied. From 2-DE serotransferrin and alpha-enolase were found differentially expressed in FM. Hence, their expression was validated by ELISA together with phosphoglycerate-mutase-I and transaldolase, which were found in a previous work. Moreover, ROC curve was calculated by comparing FM patients versus control subjects (healthy plus migraine) to investigate the discriminative power of biomarkers. The best performance was obtained by combining alpha-enolase, phosphoglycerate-mutase-I and serotransferrin. On the other hand, none of the candidate proteins showed a statistical correlation with clinical features. Finally, preliminary SELDI analysis highlighted two peaks whose identification need to be validated. Overall, these results could be useful in supporting the clinical diagnosis of FM. Significance: FM is one of the most common chronic pain condition which is associated with significant disability. The fibromyalgic pain is a peculiar characteristic of this disease and FM patients suffer from reduced quality of life, daily functioning and productivity. Considering the deep complexity of FM, the discovery of more objective markers is crucial for supporting clinical diagnosis. Therefore, the aim of the present study was the selection of biomarkers effectively associated with fibromyalgic pain which will enable clinicians to ach
- Published
- 2019
4. Brain mitochondrial proteome alteration driven by creatine deficiency suggests novel therapeutic venues for creatine deficiency syndromes
- Author
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Giusti, L, Molinaro, A, Alessandri, Mg, Boldrini, C, Ciregia, F, Lacerenza, S, Ronci, M, Urbani, Andrea, Cioni, G, Mazzoni, Mr, Pizzorusso, T, Lucacchini, A, Baroncelli, L, Urbani, A (ORCID:0000-0001-9168-3174), Giusti, L, Molinaro, A, Alessandri, Mg, Boldrini, C, Ciregia, F, Lacerenza, S, Ronci, M, Urbani, Andrea, Cioni, G, Mazzoni, Mr, Pizzorusso, T, Lucacchini, A, Baroncelli, L, and Urbani, A (ORCID:0000-0001-9168-3174)
- Abstract
Creatine (Cr) is a small metabolite with a central role in energy metabolism and mitochondria! function. Creatine deficiency syndromes are inborn errors of Cr metabolism causing Cr depletion in all body tissues and particularly in the nervous system. Patient symptoms involve intellectual disability, language and behavioral disturbances, seizures and movement disorders suggesting that brain cells are particularly sensitive to Cr depletion. Cr deficiency was found to affect metabolic activity and structural abnormalities of mitochondrial organelles; however a detailed analysis of molecular mechanisms linking Cr deficit, energy metabolism alterations and brain dysfunction is still missing. Using a proteomic approach we evaluated the proteome changes of the brain mitochondria! fraction induced by the deletion of the Cr transporter (CrT) in developing mutant mice. We found a marked alteration of the mitochondria! proteomic landscape in the brain of CrT deficient mice, with the overexpression of many proteins involved in energy metabolism and response to oxidative stress. Moreover, our data suggest possible abnormalities of dendritic spines, synaptic function and plasticity, network excitability and neuroinflammatory response. Intriguingly, the alterations occurred in coincidence with the developmental onset of neurological symptoms. Thus, cerebral mitochondria! alterations could represent an early response to Cr deficiency that could be targeted for therapeutic intervention.
- Published
- 2019
5. Shotgun proteomic analysis and protein lysine acetylation in cytokine exposed human pancreatic islets
- Author
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Ciregia, F, Grano, F, Mazzoni, Mr, Mossuto, S, Lucacchini, A, Suleiman, M, Giusti, L, De Luca, C, Lacerenza, S, Marselli, L, Ronci, M, Urbani, A, Marchetti, P, and Bugliani, M
- Published
- 2018
6. Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal beta cells and human pancreatic islets
- Author
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Ciregia, F, Bugliani, M, Ronci, M, Giusti, L, Boldrini, C, Mazzoni, Mr, Mossuto, S, Grano, F, Cnop, M, Marselli, L, Giannaccini, G, Urbani, Andrea, Lucacchini, A, Marchetti, P, Urbani, A (ORCID:0000-0001-9168-3174), Ciregia, F, Bugliani, M, Ronci, M, Giusti, L, Boldrini, C, Mazzoni, Mr, Mossuto, S, Grano, F, Cnop, M, Marselli, L, Giannaccini, G, Urbani, Andrea, Lucacchini, A, Marchetti, P, and Urbani, A (ORCID:0000-0001-9168-3174)
- Abstract
Type 2 diabetes is characterized by progressive beta cell dysfunction, with lipotoxicity playing a possible pathogenetic role. Palmitate is often used to examine the direct effects of lipotoxicity and it may cause mitochondrial alterations by activating protein acetylation. However, it is unknown whether palmitate influences protein acetylation in beta cells. We investigated lysine acetylation in mitochondrial proteins from INS-1E beta cells (INS-1E) and in proteins from human pancreatic islets (HPI) after 24 h palmitate exposure. First, we confirmed that palmitate damages beta cells and demonstrated that chemical inhibition of deacetylation also impairs INS-1E function and survival. Then, by 2-D gel electrophoresis, Western Blot and Liquid Chromatography-Mass Spectrometry we evaluated the effects of palmitate on protein acetylation. In mitochondrial preparations from palmitate-treated INS-1E, 32 acetylated spots were detected, with 13 proteins resulting over-acetylated. In HPI, 136 acetylated proteins were found, of which 11 were over-acetylated upon culture with palmitate. Interestingly, three proteins, glutamate dehydrogenase, mitochondrial superoxide dismutase, and SREBP-1, were over-acetylated in both INS-1E and HPI. Therefore, prolonged exposure to palmitate induces changes in beta cell protein lysine acetylation and this modification could play a role in causing beta cell damage. Dysregulated acetylation may be a target to counteract palmitate-induced beta cell lipotoxicity.
- Published
- 2017
7. Dietary Supplementation with Boswellia serrata, Verbascum thapsus, and Curcuma longa in Show Jumping Horses: Effects on Serum Proteome, Antioxidant Status, and Anti-Inflammatory Gene Expression
- Author
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Daniela Beghelli, Lorenzo Zallocco, Cristina Angeloni, Onelia Bistoni, Maurizio Ronci, Clarita Cavallucci, Maria Rosa Mazzoni, Anna Nuccitelli, Chiara Catalano, Silvana Hrelia, Antonio Lucacchini, Laura Giusti, and Beghelli D, Zallocco L, Angeloni C, Bistoni O, Ronci M, Cavallucci C, Mazzoni MR, Nuccitelli A, Catalano C, Hrelia S, Lucacchini A, Giusti L.
- Subjects
oxidative stre ,Space and Planetary Science ,Boswellia serrata (Roxb ex Colebr) ,Verbascum thapsus ,Curcuma longa ,sport horses ,serum proteome ,oxidative stress ,inflammation ,immune responses ,Paleontology ,sport horse ,Verbascum thapsu ,General Biochemistry, Genetics and Molecular Biology ,Ecology, Evolution, Behavior and Systematics - Abstract
Intense exercise can cause inflammation and oxidative stress due to the production of reactive oxygen species. These pathophysiological processes are interdependent, and each one can induce the other, creating a vicious circle. A placebo-controlled blind study was carried out in show jumping horses (n. 16) to evaluate the effects of a commercial dietary supplement (Dolhorse® N.B.F. Lanes srl, Milan, Italy) containing Verbascum thapsus leaf powder (1.42%), Curcuma longa (14.280 mg/kg), and Boswellia serrata (Roxb ex Colebr) (14.280 mg/kg) extracts. Before and after 10 days of dietary supplementation, blood samples were collected to evaluate the protein levels, antioxidants, and inflammatory responses by proteomic analysis or real-time Reverse Transcriptase-Polymerase Chain Reaction (real-time RT-PCR). A total of 36 protein spots, connected to 29 proteins, were modulated by dietary supplementation, whereas real-time RT-PCR revealed a significant downregulation of proinflammatory cytokines (interleukin 1α (p < 0.05) and interleukin-6 (0.005), toll-like receptor 4 (p < 0.05), and IKBKB (p < 0.05) in supplemented sport horses. Immunoglobulin chains, gelsolin, plasminogen, vitamin D binding protein, apolipoprotein AIV, and filamin B were overexpressed, whereas haptoglobin, α-2-HS-glycoprotein, α2-macroglobulin, afamin, amine oxidase, 60S acidic ribosomal protein, and complement fragments 3, 4, and 7 were reduced. No effect was observed on the antioxidant defense systems. The present results suggest this phytotherapy may reinforce the innate immune responses, thus representing a valid adjuvant to alleviate inflammation, which is a pathophysiological process in sport horses.
- Published
- 2023
8. Antioxidant and Neuroprotective Activity of Extra Virgin Olive Oil Extracts Obtained from Quercetano Cultivar Trees Grown in Different Areas of the Tuscany Region (Italy)
- Author
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Silvana Hrelia, Dennis Fiorini, Antonio Lucacchini, Serena Scortichini, Cristina Angeloni, Daniela Beghelli, Maria Rosa Mazzoni, Maria Cristina Barbalace, Lorenzo Zallocco, Marco Macchia, Laura Giusti, Maurizio Ronci, Maria Digiacomo, and Barbalace MC, Zallocco L, Beghelli D, Ronci M, Scortichini S, Digiacomo M, Macchia M, Mazzoni MR, Fiorini D, Lucacchini A, Hrelia S, Giusti L, Angeloni C.
- Subjects
0301 basic medicine ,antioxidant ,Antioxidant ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,Glutathione reductase ,phenols ,Author Keywords: olive oil ,medicine.disease_cause ,neurotrophins ,Biochemistry ,chemistry.chemical_compound ,0302 clinical medicine ,phenol ,oxidative stress ,chemistry.chemical_classification ,Chemistry ,neurotrophin ,NEUROTROPHIC FACTORS ,PHENOLIC-COMPOUNDS ,olive oil ,MEDITERRANEAN DIET ,ALZHEIMERS-DISEASE ,antioxidants ,neuroprotection ,OLEUROPEIN AGLYCONE ,MITOCHONDRIAL DYSFUNCTION ,NEURONAL DIFFERENTIATION ,Flavones ,Neuroprotection ,QUANTITATIVE METHOD ,Article ,03 medical and health sciences ,proteomics ,Oleocanthal ,medicine ,Phenols ,Molecular Biology ,oxidative stre ,lcsh:RM1-950 ,proteomics KeyWords Plus: BDNF MESSENGER-RNA ,OXIDATIVE STRESS ,Cell Biology ,Heme oxygenase ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
Neurodegenerative diseases are driven by several mechanisms such as inflammation, abnormal protein aggregation, excitotoxicity, mitochondrial dysfunction and oxidative stress. So far, no therapeutic strategies are available for neurodegenerative diseases and in recent years the research is focusing on bioactive molecules present in food. In particular, extra-virgin olive oil (EVOO) phenols have been associated to neuroprotection. In this study, we investigated the potential antioxidant and neuroprotective activity of two different EVOO extracts obtained from Quercetano cultivar trees grown in two different areas (plain and hill) of the Tuscany region (Italy). The different geographical origin of the orchards influenced phenol composition. Plain extract presented a higher content of phenyl ethyl alcohols, cinnammic acids, oleacein, oleocanthal and flavones, meanwhile, hill extract was richer in lignans. Hill extract was more effective in protecting differentiated SH-SY5Y cells from peroxide stress thanks to a marked upregulation of the antioxidant enzymes heme oxygenase 1, NADPH quinone oxidoreductase 1, thioredoxin Reductase 1 and glutathione reductase. Proteomic analysis revealed that hill extract plays a role in the regulation of proteins involved in neuronal plasticity and activation of neurotrophic factors such as BDNF. In conclusion, these data demonstrate that EVOOs can have important neuroprotective activities, but these effects are strictly related to their specific phenol composition.
- Published
- 2021
- Full Text
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9. Correction: Proteomic Profiling Reveals Specific Molecular Hallmarks of the Pig Claustrum.
- Author
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Pirone A, Ciregia F, Lazzarini G, Miragliotta V, Ronci M, Zuccarini M, Zallocco L, Beghelli D, Mazzoni MR, Lucacchini A, and Giusti L
- Published
- 2024
- Full Text
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10. Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells.
- Author
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Silvestri R, Zallocco L, Corrado A, Ronci M, Aceto R, Ricci B, Cipollini M, Dell'Anno I, De Simone C, De Marco G, Ferrarini E, Beghelli D, Mazzoni MR, Lucacchini A, Gemignani F, Giusti L, and Landi S
- Abstract
Introduction: The single nucleotide polymorphism (SNP) rs4644 at codon 64 of galectin-3 (gal-3, gene name: LGALS3 ), specifying the variant proline (P64) to histidine (H64), is known to affect the protein's functions and has been associated with the risk of several types of cancer, including differentiated thyroid carcinoma (DTC)., Materials and Methods: To deepen our understanding of the biological effects of this SNP, we analyzed the proteome of two isogenic cell lines (NC-P64 vs. NA-H64) derived from the immortalized non-malignant thyrocyte cell line Nthy-Ori, generated through the CRISPR-Cas9 technique to differ by rs4644 genotype. We compared the proteome of these cells to detect differentially expressed proteins and studied their proteome in relation to their transcriptome., Results: Firstly, we found, consistently with previous studies, that gal-3-H64 could be detected as a monomer, homodimer, and heterodimer composed of one cleaved and one uncleaved monomer, whereas gal-3-P64 could be found only as a monomer or uncleaved homodimer. Moreover, results indicate that rs4644 influences the expression of several proteins, predominantly upregulated in NA-H64 cells. Overall, the differential protein expression could be attributed to the altered mRNA expression, suggesting that rs4644 shapes the function of gal-3 as a transcriptional co-regulator. However, this SNP also appeared to affect post-transcriptional regulatory mechanisms for proteins whose expression was oppositely regulated compared to mRNA expression. It is conceivable that the rs4644-dependent activities of gal-3 could be ascribed to the different modalities of self-dimerization., Conclusion: Our study provided further evidence that rs4644 could affect the gal-3 functions through several routes, which could be at the base of differential susceptibility to diseases, as reported in case-control association studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Silvestri, Zallocco, Corrado, Ronci, Aceto, Ricci, Cipollini, Dell’Anno, De Simone, De Marco, Ferrarini, Beghelli, Mazzoni, Lucacchini, Gemignani, Giusti and Landi.)
- Published
- 2024
- Full Text
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11. Integrative neuro-cardiovascular dynamics in response to test anxiety: A brain-heart axis study.
- Author
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Catrambone V, Zallocco L, Ramoretti E, Mazzoni MR, Sebastiani L, and Valenza G
- Subjects
- Humans, Heart physiology, Brain physiology, Anxiety, Heart Rate physiology, Test Anxiety, Cardiovascular System
- Abstract
Test anxiety (TA), a recognized form of social anxiety, is the most prominent cause of anxiety among students and, if left unmanaged, can escalate to psychiatric disorders. TA profoundly impacts both central and autonomic nervous systems, presenting as a dual manifestation of cognitive and autonomic components. While limited studies have explored the physiological underpinnings of TA, none have directly investigated the intricate interplay between the CNS and ANS in this context. In this study, we introduce a non-invasive, integrated neuro-cardiovascular approach to comprehensively characterize the physiological responses of 27 healthy subjects subjected to test anxiety induced via a simulated exam scenario. Our experimental findings highlight that an isolated analysis of electroencephalographic and heart rate variability data fails to capture the intricate information provided by a brain-heart axis assessment, which incorporates an analysis of the dynamic interaction between the brain and heart. With respect to resting state, the simulated examination induced a decrease in the neural control onto heartbeat dynamics at all frequencies, while the studying condition induced a decrease in the ascending heart-to-brain interplay at EEG oscillations up to 12Hz. This underscores the significance of adopting a multisystem perspective in understanding the complex and especially functional directional mechanisms underlying test anxiety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
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12. Proteomic Profiling Reveals Specific Molecular Hallmarks of the Pig Claustrum.
- Author
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Pirone A, Ciregia F, Lazzarini G, Miragliotta V, Ronci M, Zuccarini M, Zallocco L, Beghelli D, Mazzoni MR, Lucacchini A, and Giusti L
- Subjects
- Humans, Animals, Swine, Endocannabinoids metabolism, Proteomics, Neurons metabolism, Brain, Claustrum metabolism
- Abstract
The present study, employing a comparative proteomic approach, analyzes the protein profile of pig claustrum (CLA), putamen (PU), and insula (IN). Pig brain is an interesting model whose key translational features are its similarities with cortical and subcortical structures of human brain. A greater difference in protein spot expression was observed in CLA vs PU as compared to CLA vs IN. The deregulated proteins identified in CLA resulted to be deeply implicated in neurodegenerative (i.e., sirtuin 2, protein disulfide-isomerase 3, transketolase) and psychiatric (i.e., copine 3 and myelin basic protein) disorders in humans. Metascape analysis of differentially expressed proteins in CLA vs PU comparison suggested activation of the α-synuclein pathway and L1 recycling pathway corroborating the involvement of these anatomical structures in neurodegenerative diseases. The expression of calcium/calmodulin-dependent protein kinase and dihydropyrimidinase like 2, which are linked to these pathways, was validated using western blot analysis. Moreover, the protein data set of CLA vs PU comparison was analyzed by Ingenuity Pathways Analysis to obtain a prediction of most significant canonical pathways, upstream regulators, human diseases, and biological functions. Interestingly, inhibition of presenilin 1 (PSEN1) upstream regulator and activation of endocannabinoid neuronal synapse pathway were observed. In conclusion, this is the first study presenting an extensive proteomic analysis of pig CLA in comparison with adjacent areas, IN and PUT. These results reinforce the common origin of CLA and IN and suggest an interesting involvement of CLA in endocannabinoid circuitry, neurodegenerative, and psychiatric disorders in humans., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
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13. Dietary Supplementation with Boswellia serrata, Verbascum thapsus, and Curcuma longa in Show Jumping Horses: Effects on Serum Proteome, Antioxidant Status, and Anti-Inflammatory Gene Expression.
- Author
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Beghelli D, Zallocco L, Angeloni C, Bistoni O, Ronci M, Cavallucci C, Mazzoni MR, Nuccitelli A, Catalano C, Hrelia S, Lucacchini A, and Giusti L
- Abstract
Intense exercise can cause inflammation and oxidative stress due to the production of reactive oxygen species. These pathophysiological processes are interdependent, and each one can induce the other, creating a vicious circle. A placebo-controlled blind study was carried out in show jumping horses (n. 16) to evaluate the effects of a commercial dietary supplement (Dolhorse
® N.B.F. Lanes srl, Milan, Italy) containing Verbascum thapsus leaf powder (1.42%), Curcuma longa (14.280 mg/kg), and Boswellia serrata (Roxb ex Colebr) (14.280 mg/kg) extracts. Before and after 10 days of dietary supplementation, blood samples were collected to evaluate the protein levels, antioxidants, and inflammatory responses by proteomic analysis or real-time Reverse Transcriptase-Polymerase Chain Reaction (real-time RT-PCR). A total of 36 protein spots, connected to 29 proteins, were modulated by dietary supplementation, whereas real-time RT-PCR revealed a significant downregulation of proinflammatory cytokines (interleukin 1α ( p < 0.05) and interleukin-6 (0.005), toll-like receptor 4 ( p < 0.05), and IKBKB ( p < 0.05) in supplemented sport horses. Immunoglobulin chains, gelsolin, plasminogen, vitamin D binding protein, apolipoprotein AIV, and filamin B were overexpressed, whereas haptoglobin, α-2-HS-glycoprotein, α2-macroglobulin, afamin, amine oxidase, 60S acidic ribosomal protein, and complement fragments 3, 4, and 7 were reduced. No effect was observed on the antioxidant defense systems. The present results suggest this phytotherapy may reinforce the innate immune responses, thus representing a valid adjuvant to alleviate inflammation, which is a pathophysiological process in sport horses.- Published
- 2023
- Full Text
- View/download PDF
14. Role of Prosaposin and Extracellular Sulfatase Sulf-1 Detection in Pleural Effusions as Diagnostic Biomarkers of Malignant Mesothelioma.
- Author
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Zallocco L, Silvestri R, Ciregia F, Bonotti A, Marino R, Foddis R, Lucacchini A, Giusti L, and Mazzoni MR
- Abstract
Malignant pleural mesothelioma is an aggressive malignancy with poor prognosis. Unilateral pleural effusion is frequently the initial clinical sign requiring therapeutic thoracentesis, which also offers a diagnostic opportunity. Detection of soluble biomarkers can support diagnosis, but few show good diagnostic accuracy. Here, we studied the expression levels and discriminative power of two putative biomarkers, prosaposin and extracellular sulfatase SULF-1, identified by proteomic and transcriptomic analysis, respectively. Pleural effusions from a total of 44 patients (23 with mesothelioma, 8 with lung cancer, and 13 with non-malignant disease) were analyzed for prosaposin and SULF-1 by enzyme-linked immunosorbent assay. Pleural effusions from mesothelioma patients had significantly higher levels of prosaposin and SULF-1 than those from non-malignant disease patients. Receiver-operating characteristic (ROC) analysis showed that both biomarkers have good discriminating power as pointed out by an AUC value of 0.853 (p = 0.0005) and 0.898 (p < 0.0001) for prosaposin and SULF-1, respectively. Combining data ensued a model predicting improvement of the diagnostic performance (AUC = 0.916, p < 0.0001). In contrast, prosaposin couldn’t discriminate mesothelioma patients from lung cancer patients while ROC analysis of SULF-1 data produced an AUC value of 0.821 (p = 0.0077) but with low sensitivity. In conclusion, prosaposin and SULF-1 levels determined in pleural effusion may be promising biomarkers for differential diagnosis between mesothelioma and non-malignant pleural disease. Instead, more patients need to be enrolled before granting the possible usefulness of these soluble proteins in differentiating mesothelioma pleural effusions from those linked to lung cancer.
- Published
- 2022
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15. The Protective Action of Metformin against Pro-Inflammatory Cytokine-Induced Human Islet Cell Damage and the Mechanisms Involved.
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Giusti L, Tesi M, Ciregia F, Marselli L, Zallocco L, Suleiman M, De Luca C, Del Guerra S, Zuccarini M, Trerotola M, Eizirik DL, Cnop M, Mazzoni MR, Marchetti P, Lucacchini A, and Ronci M
- Subjects
- Caspase 3 metabolism, Cytokines metabolism, Glucose metabolism, Glucose toxicity, Humans, Insulin metabolism, Diabetes Mellitus, Type 1 metabolism, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 metabolism, Islets of Langerhans metabolism, Metformin pharmacology
- Abstract
Metformin, a drug widely used in type 2 diabetes (T2D), has been shown to protect human β-cells exposed to gluco- and/or lipotoxic conditions and those in islets from T2D donors. We assessed whether metformin could relieve the human β-cell stress induced by pro-inflammatory cytokines (which mediate β-cells damage in type 1 diabetes, T1D) and investigated the underlying mechanisms using shotgun proteomics. Human islets were exposed to 50 U/mL interleukin-1β plus 1000 U/mL interferon-γ for 48 h, with or without 2.4 µg/mL metformin. Glucose-stimulated insulin secretion (GSIS) and caspase 3/7 activity were studied, and a shotgun label free proteomics analysis was performed. Metformin prevented the reduction of GSIS and the activation of caspase 3/7 induced by cytokines. Proteomics analysis identified more than 3000 proteins in human islets. Cytokines alone altered the expression of 244 proteins (145 up- and 99 down-regulated), while, in the presence of metformin, cytokine-exposure modified the expression of 231 proteins (128 up- and 103 downregulated). Among the proteins inversely regulated in the two conditions, we found proteins involved in vesicle motility, defense against oxidative stress (including peroxiredoxins), metabolism, protein synthesis, glycolysis and its regulation, and cytoskeletal proteins. Metformin inhibited pathways linked to inflammation, immune reactions, mammalian target of rapamycin (mTOR) signaling, and cell senescence. Some of the changes were confirmed by Western blot. Therefore, metformin prevented part of the deleterious actions of pro-inflammatory cytokines in human β-cells, which was accompanied by islet proteome modifications. This suggests that metformin, besides use in T2D, might be considered for β-cell protection in other types of diabetes, possibly including early T1D.
- Published
- 2022
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16. Parathyroid Carcinoma and Adenoma Co-existing in One Patient: Case Report and Comparative Proteomic Analysis.
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Ciregia F, Cetani F, Pardi E, Soggiu A, Piras C, Zallocco L, Borsari S, Ronci M, Caruso V, Marcocci C, Mazzoni MR, Lucacchini A, and Giusti L
- Subjects
- Adenoma pathology, Humans, Male, Middle Aged, Parathyroid Neoplasms pathology, Adenoma diagnosis, Parathyroid Neoplasms diagnosis, Proteomics methods
- Abstract
Background/aim: The lack of specific parathyroid carcinoma (PC) biomarkers in clinical practice points out the importance of analyzing the proteomic signature of this cancer. We performed a comparative proteomic analysis of PC and parathyroid adenoma (PA) co-existing in the same patient., Patients and Methods: PC and PA were taken from a 63-year-old patient. Using two-dimensional differential gel electrophoresis (2D-DIGE) coupled to mass spectrometry we examined the differences between PC and PA proteins. For validation, additional PC and PA samples were obtained from 10 patients. Western blot analysis was used to validate the difference of expression observed with 2D-DIGE analysis. Bioinfomatic analysis was performed using QIAGEN's Ingenuity Pathways Analysis (IPA) to determine the predominant canonical pathways and interaction networks involved., Results: Thirty-three differentially expressed proteins were identified in PC compared to PA. Among these, ubiquitin C-terminal hydrolase-L1 (UCH-L1) was highly overexpressed in PC. The result was confirmed by Western Blot analysis in additional PC samples., Conclusion: Our comparative proteomic analysis of co-existing neoplasms allowed detecting specific and peculiar differences between PC and PA overcoming population biological variability., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2021
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17. Salivary Proteome Changes in Response to Acute Psychological Stress Due to an Oral Exam Simulation in University Students: Effect of an Olfactory Stimulus.
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Zallocco L, Giusti L, Ronci M, Mussini A, Trerotola M, Mazzoni MR, Lucacchini A, and Sebastiani L
- Subjects
- Adult, Anxiety Disorders metabolism, Biomarkers analysis, Female, Humans, Male, Proteome analysis, Stress, Psychological metabolism, Universities, Young Adult, Anxiety Disorders diagnosis, Biomarkers metabolism, Proteome metabolism, Saliva metabolism, Salivary Proteins and Peptides metabolism, Stress, Psychological diagnosis, Students psychology
- Abstract
The autonomic nervous system (ANS) plays a crucial role both in acute and chronic psychological stress eliciting changes in many local and systemic physiological and biochemical processes. Salivary secretion is also regulated by ANS. In this study, we explored salivary proteome changes produced in thirty-eight University students by a test stress, which simulated an oral exam. Students underwent a relaxation phase followed by the stress test during which an electrocardiogram was recorded. To evaluate the effect of an olfactory stimulus, half of the students were exposed to a pleasant odor diffused in the room throughout the whole session. Saliva samples were collected after the relaxation phase (T0) and the stress test (T1). State anxiety was also evaluated at T0 and T1. Salivary proteins were separated by two-dimensional electrophoresis, and patterns at different times were compared. Spots differentially expressed were trypsin digested and identified by mass spectrometry. Western blot analysis was used to validate proteomic results. Anxiety scores and heart rate changes indicated that the fake exam induced anxiety. Significant changes of α-amylase, polymeric immunoglobulin receptor (PIGR), and immunoglobulin α chain (IGHA) secretion were observed after the stress test was performed in the two conditions. Moreover, the presence of pleasant odor reduced the acute social stress affecting salivary proteome changes. Therefore, saliva proteomic analysis was a useful approach to evaluate the rapid responses associated to an acute stress test also highlighting known biomarkers.
- Published
- 2021
- Full Text
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18. Antioxidant and Neuroprotective Activity of Extra Virgin Olive Oil Extracts Obtained from Quercetano Cultivar Trees Grown in Different Areas of the Tuscany Region (Italy).
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Barbalace MC, Zallocco L, Beghelli D, Ronci M, Scortichini S, Digiacomo M, Macchia M, Mazzoni MR, Fiorini D, Lucacchini A, Hrelia S, Giusti L, and Angeloni C
- Abstract
Neurodegenerative diseases are driven by several mechanisms such as inflammation, abnormal protein aggregation, excitotoxicity, mitochondrial dysfunction and oxidative stress. So far, no therapeutic strategies are available for neurodegenerative diseases and in recent years the research is focusing on bioactive molecules present in food. In particular, extra-virgin olive oil (EVOO) phenols have been associated to neuroprotection. In this study, we investigated the potential antioxidant and neuroprotective activity of two different EVOO extracts obtained from Quercetano cultivar trees grown in two different areas (plain and hill) of the Tuscany region (Italy). The different geographical origin of the orchards influenced phenol composition. Plain extract presented a higher content of phenyl ethyl alcohols, cinnammic acids, oleacein, oleocanthal and flavones; meanwhile, hill extract was richer in lignans. Hill extract was more effective in protecting differentiated SH-SY5Y cells from peroxide stress thanks to a marked upregulation of the antioxidant enzymes heme oxygenase 1, NADPH quinone oxidoreductase 1, thioredoxin Reductase 1 and glutathione reductase. Proteomic analysis revealed that hill extract plays a role in the regulation of proteins involved in neuronal plasticity and activation of neurotrophic factors such as BDNF. In conclusion, these data demonstrate that EVOOs can have important neuroprotective activities, but these effects are strictly related to their specific phenol composition.
- Published
- 2021
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19. Focus on Human Monoamine Transporter Selectivity. New Human DAT and NET Models, Experimental Validation, and SERT Affinity Exploration.
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Ortore G, Orlandini E, Betti L, Giannaccini G, Mazzoni MR, Camodeca C, and Nencetti S
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- Animals, Binding Sites, Dopamine Plasma Membrane Transport Proteins metabolism, Humans, Models, Theoretical, Rabbits, Norepinephrine Plasma Membrane Transport Proteins metabolism, Serotonin Plasma Membrane Transport Proteins metabolism, Selective Serotonin Reuptake Inhibitors
- Abstract
The most commonly used antidepressant drugs are the serotonin transporter inhibitors. Their effects depend strongly on the selectivity for a single monoamine transporter compared to other amine transporters or receptors, and the selectivity is roughly influenced by the spatial protein structure. Here, we provide a computational study on three human monoamine transporters, i.e., DAT, NET, and SERT. Starting from the construction of hDAT and hNET models, whose three-dimensional structure is unknown, and the prediction of the binding pose for 19 known inhibitors, 3D-QSAR models of three human transporters were built. The training set variability, which was high in structure and activity profile, was validated using a set of in-house compounds. Results concern more than one aspect. First of all, hDAT and hNET three-dimensional structures were built, validated, and compared to the hSERT one; second, the computational study highlighted the differences in binding site arrangement statistically correlated to inhibitor selectivity; third, the profiling of new inhibitors pointed out a conservation of the inhibitory activity trend between rabbit and human SERT with a difference of about 1 order of magnitude; fourth, binding and functional studies confirmed 4-(benzyloxy)-4-phenylpiperidine 20a-d and 21a-d as potent SERT inhibitors. In particular, one of the compounds (compound 20b) revealed a higher affinity for SERT than paroxetine in human platelets.
- Published
- 2020
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20. Proteomic Investigation of Malignant Major Salivary Gland Tumors.
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Seccia V, Navari E, Donadio E, Boldrini C, Ciregia F, Ronci M, Aceto A, Dallan I, Lucacchini A, Casani AP, Mazzoni MR, and Giusti L
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- Adenolymphoma diagnosis, Adenoma, Pleomorphic diagnosis, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor analysis, Biopsy, Fine-Needle, Female, Humans, Male, Middle Aged, Proteomics, Biomarkers, Tumor metabolism, Salivary Gland Neoplasms diagnosis
- Abstract
The purpose of this study was to define the proteome profile of fine needle aspiration (FNA) samples of malignant major salivary gland tumors (MSGT) compared to benign counterparts, and to evaluate potential clinical correlations and future applications. Patients affected by MSGT (n = 20), pleomorphic adenoma (PA) (n = 37) and Warthin's tumor (WT) (n = 14) were enrolled. Demographic, clinical and histopathological data were registered for all patients. FNA samples were processed to obtain the protein extracts. Protein separation was obtained by two-dimensional electrophoresis (2-DE) and proteins were identified by mass spectrometry. Western blot analysis was performed to validate the 2-DE results. Statistical differences between groups were calculated by the Mann-Whitney U test for non-normal data. Spearman's rank correlation coefficient was calculated to evaluate correlations among suggested protein biomarkers and clinical parameters. Twelve and 27 differentially expressed spots were found for MSGT versus PA and MSGT versus WT, respectively. Among these, annexin-5, cofilin-1, peptidyl-prolyl-cis-trans-isomerase-A and F-actin-capping-alpha-1 were able to differentiate MSGT from PA, WT, and healthy samples. Moreover, STRING analysis suggested cofilin-1 as a key node of protein interactions. Some of the overexpressed proteins are related to some clinical factors of our cohort, such as survival and outcome. Our results suggest potential protein biomarkers of MSGT, which could allow for more appropriate treatment plans, as well as shedding light on the molecular pathways involved.
- Published
- 2020
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21. Putative Biomarkers for Malignant Pleural Mesothelioma Suggested by Proteomic Analysis of Cell Secretome.
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Lacerenza S, Ciregia F, Giusti L, Bonotti A, Greco V, Giannaccini G, D'Antongiovanni V, Fallahi P, Pieroni L, Cristaudo A, Lucacchini A, Mazzoni MR, and Foddis R
- Subjects
- Aged, Case-Control Studies, Cell Line, Tumor, Female, GPI-Linked Proteins blood, Humans, Lung Neoplasms pathology, Male, Mesothelin, Mesothelioma pathology, Mesothelioma, Malignant, Middle Aged, Oxidoreductases Acting on Sulfur Group Donors blood, Pleural Neoplasms pathology, ROC Curve, Saposins blood, Secretory Pathway, Biomarkers, Tumor blood, Lung Neoplasms blood, Mesothelioma blood, Pleural Neoplasms blood, Proteome metabolism
- Abstract
Background: Malignant pleural mesothelioma (MPM) a rare neoplasm linked to asbestos exposure is characterized by a poor prognosis. Soluble mesothelin is currently considered the most specific diagnostic biomarker. The aim of the study was to identify novel biomarkers by proteomic analysis of two MPM cell lines secretome., Materials and Methods: The protein patterns of MPM cells secretome were examined and compared to a non-malignant mesothelial cell line using two-dimensional gel electrophoresis coupled to mass spectrometry. Serum levels of candidate biomarkers were determined in MPM patients and control subjects., Results: Two up-regulated proteins involved in cancer biology, prosaposin and quiescin Q6 sulfhydryl oxidase 1, were considered candidate biomarkers. Serum levels of both proteins were significantly higher in MPM patients than control subjects. Combining the data of each receiver-operating characteristic analysis predicted a good diagnostic accuracy., Conclusion: A panel of the putative biomarkers represents a promising tool for MPM diagnosis., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2020
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22. Brain mitochondrial proteome alteration driven by creatine deficiency suggests novel therapeutic venues for creatine deficiency syndromes.
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Giusti L, Molinaro A, Alessandrì MG, Boldrini C, Ciregia F, Lacerenza S, Ronci M, Urbani A, Cioni G, Mazzoni MR, Pizzorusso T, Lucacchini A, and Baroncelli L
- Subjects
- Animals, Energy Metabolism physiology, Membrane Transport Proteins genetics, Mice, Neuronal Plasticity physiology, Proteome, Brain metabolism, Creatine deficiency, Membrane Transport Proteins metabolism, Mitochondria metabolism, Neurons metabolism
- Abstract
Creatine (Cr) is a small metabolite with a central role in energy metabolism and mitochondrial function. Creatine deficiency syndromes are inborn errors of Cr metabolism causing Cr depletion in all body tissues and particularly in the nervous system. Patient symptoms involve intellectual disability, language and behavioral disturbances, seizures and movement disorders suggesting that brain cells are particularly sensitive to Cr depletion. Cr deficiency was found to affect metabolic activity and structural abnormalities of mitochondrial organelles; however a detailed analysis of molecular mechanisms linking Cr deficit, energy metabolism alterations and brain dysfunction is still missing. Using a proteomic approach we evaluated the proteome changes of the brain mitochondrial fraction induced by the deletion of the Cr transporter (CrT) in developing mutant mice. We found a marked alteration of the mitochondrial proteomic landscape in the brain of CrT deficient mice, with the overexpression of many proteins involved in energy metabolism and response to oxidative stress. Moreover, our data suggest possible abnormalities of dendritic spines, synaptic function and plasticity, network excitability and neuroinflammatory response. Intriguingly, the alterations occurred in coincidence with the developmental onset of neurological symptoms. Thus, cerebral mitochondrial alterations could represent an early response to Cr deficiency that could be targeted for therapeutic intervention., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2019
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23. Putative salivary biomarkers useful to differentiate patients with fibromyalgia.
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Ciregia F, Giacomelli C, Giusti L, Boldrini C, Piga I, Pepe P, Consensi A, Gori S, Lucacchini A, Mazzoni MR, and Bazzichi L
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- Adult, Arthritis, Rheumatoid diagnosis, Biomarkers analysis, Case-Control Studies, Chronic Pain, Diagnosis, Differential, Female, Fibromyalgia pathology, Humans, Male, Middle Aged, Fibromyalgia diagnosis, Proteomics methods, Salivary Proteins and Peptides analysis
- Abstract
Fibromyalgia (FM) is a chronic pain disorder characterized by widespread pain and associated with unspecific symptoms. So far, no laboratory tests have been validated. The aim of the present study was to investigate the presence in saliva of potential diagnostic and/or prognostic biomarkers which could be useful for the management of FM patients. Specifically, the salivary profile of FM patients was compared with those of healthy subjects, subjects suffering migraine (model of non-inflammatory chronic pain), and patients affected by rheumatoid arthritis (model of inflammatory chronic pain). For proteomics analysis 2-DE and SELDI-TOF-MS were applied. From 2-DE serotransferrin and alpha-enolase were found differentially expressed in FM. Hence, their expression was validated by ELISA together with phosphoglycerate-mutase-I and transaldolase, which were found in a previous work. Moreover, ROC curve was calculated by comparing FM patients versus control subjects (healthy plus migraine) to investigate the discriminative power of biomarkers. The best performance was obtained by combining alpha-enolase, phosphoglycerate-mutase-I and serotransferrin. On the other hand, none of the candidate proteins showed a statistical correlation with clinical features. Finally, preliminary SELDI analysis highlighted two peaks whose identification need to be validated. Overall, these results could be useful in supporting the clinical diagnosis of FM. SIGNIFICANCE: FM is one of the most common chronic pain condition which is associated with significant disability. The fibromyalgic pain is a peculiar characteristic of this disease and FM patients suffer from reduced quality of life, daily functioning and productivity. Considering the deep complexity of FM, the discovery of more objective markers is crucial for supporting clinical diagnosis. Therefore, the aim of the present study was the selection of biomarkers effectively associated with fibromyalgic pain which will enable clinicians to achieve an unambiguous diagnosis, and to improve approaches to patients' management. We defined a panel of 3 salivary proteins which could be one of the criteria to be taken into account. Consequently, the identification of disease salivary biomarkers could be helpful in detecting FM clusters and targeted treatment. Actually, our future perspective foresees to develop a simple, rapid and not invasive point-of-care testing which will be of use during the diagnostic process. In addition, the present results can offer a clue for shedding light upon the complex entity of such a disease like FM., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2019
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24. A Proteomic Approach to Uncover Neuroprotective Mechanisms of Oleocanthal against Oxidative Stress.
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Giusti L, Angeloni C, Barbalace MC, Lacerenza S, Ciregia F, Ronci M, Urbani A, Manera C, Digiacomo M, Macchia M, Mazzoni MR, Lucacchini A, and Hrelia S
- Subjects
- Aging drug effects, Aldehydes chemistry, Antioxidants chemistry, Antioxidants pharmacology, Apoptosis drug effects, Cell Line, Cell Survival drug effects, Cyclopentane Monoterpenes, Humans, Hydrogen Peroxide toxicity, Inflammation chemically induced, Inflammation pathology, Neurodegenerative Diseases genetics, Neurodegenerative Diseases pathology, Neuroprotective Agents pharmacology, Oxidative Stress genetics, Phenols chemistry, Plant Oils chemistry, Plant Oils pharmacology, Proteomics, Reactive Oxygen Species metabolism, Aldehydes pharmacology, Inflammation drug therapy, Neurodegenerative Diseases drug therapy, Oxidative Stress drug effects, Phenols pharmacology
- Abstract
Neurodegenerative diseases represent a heterogeneous group of disorders that share common features like abnormal protein aggregation, perturbed Ca
2+ homeostasis, excitotoxicity, impairment of mitochondrial functions, apoptosis, inflammation, and oxidative stress. Despite recent advances in the research of biomarkers, early diagnosis, and pharmacotherapy, there are no treatments that can halt the progression of these age-associated neurodegenerative diseases. Numerous epidemiological studies indicate that long-term intake of a Mediterranean diet, characterized by a high consumption of extra virgin olive oil, correlates with better cognition in aged populations. Olive oil phenolic compounds have been demonstrated to have different biological activities like antioxidant, antithrombotic, and anti-inflammatory activities. Oleocanthal, a phenolic component of extra virgin olive oil, is getting more and more scientific attention due to its interesting biological activities. The aim of this research was to characterize the neuroprotective effects of oleocanthal against H₂O₂-induced oxidative stress in neuron-like SH-SY5Y cells. Moreover, protein expression profiling, combined with pathways analyses, was used to investigate the molecular events related to the protective effects. Oleocanthal was demonstrated to counteract oxidative stress, increasing cell viability, reducing reactive oxygen species (ROS) production, and increasing reduced glutathione (GSH) intracellular level. Proteomic analysis revealed that oleocanthal significantly modulates 19 proteins in the presence of H₂O₂. In particular, oleocanthal up-regulated proteins related to the proteasome, the chaperone heat shock protein 90, the glycolytic enzyme pyruvate kinase, and the antioxidant enzyme peroxiredoxin 1. Moreover, oleocanthal protection seems to be mediated by Akt activation. These data offer new insights into the molecular mechanisms behind oleocanthal protection against oxidative stress.- Published
- 2018
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25. Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal β cells and human pancreatic islets.
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Ciregia F, Bugliani M, Ronci M, Giusti L, Boldrini C, Mazzoni MR, Mossuto S, Grano F, Cnop M, Marselli L, Giannaccini G, Urbani A, Lucacchini A, and Marchetti P
- Subjects
- Acetylation, Cell Survival drug effects, Glucose metabolism, Humans, Mitochondria drug effects, Mitochondria metabolism, Insulin-Secreting Cells drug effects, Insulin-Secreting Cells metabolism, Islets of Langerhans drug effects, Islets of Langerhans metabolism, Palmitates pharmacology, Protein Processing, Post-Translational drug effects
- Abstract
Type 2 diabetes is characterized by progressive β cell dysfunction, with lipotoxicity playing a possible pathogenetic role. Palmitate is often used to examine the direct effects of lipotoxicity and it may cause mitochondrial alterations by activating protein acetylation. However, it is unknown whether palmitate influences protein acetylation in β cells. We investigated lysine acetylation in mitochondrial proteins from INS-1E β cells (INS-1E) and in proteins from human pancreatic islets (HPI) after 24 h palmitate exposure. First, we confirmed that palmitate damages β cells and demonstrated that chemical inhibition of deacetylation also impairs INS-1E function and survival. Then, by 2-D gel electrophoresis, Western Blot and Liquid Chromatography-Mass Spectrometry we evaluated the effects of palmitate on protein acetylation. In mitochondrial preparations from palmitate-treated INS-1E, 32 acetylated spots were detected, with 13 proteins resulting over-acetylated. In HPI, 136 acetylated proteins were found, of which 11 were over-acetylated upon culture with palmitate. Interestingly, three proteins, glutamate dehydrogenase, mitochondrial superoxide dismutase, and SREBP-1, were over-acetylated in both INS-1E and HPI. Therefore, prolonged exposure to palmitate induces changes in β cell protein lysine acetylation and this modification could play a role in causing β cell damage. Dysregulated acetylation may be a target to counteract palmitate-induced β cell lipotoxicity.
- Published
- 2017
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26. Serum mesothelin, osteopontin and vimentin: useful markers for clinical monitoring of malignant pleural mesothelioma.
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Bonotti A, Simonini S, Pantani E, Giusti L, Donadio E, Mazzoni MR, Chella A, Marconi L, Ambrosino N, Lucchi M, Mussi A, Cristaudo A, and Foddis R
- Subjects
- Aged, Combined Modality Therapy, Disease Progression, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Humans, Lung Neoplasms blood, Lung Neoplasms therapy, Male, Mesothelin, Mesothelioma blood, Mesothelioma therapy, Mesothelioma, Malignant, Neoplasm Staging, Pleural Neoplasms blood, Prognosis, ROC Curve, Survival Rate, Biomarkers, Tumor blood, GPI-Linked Proteins blood, Lung Neoplasms pathology, Mesothelioma pathology, Osteopontin blood, Pleural Neoplasms pathology, Vimentin blood
- Abstract
Introduction: Malignant pleural mesothelioma (MPM) is a relatively rare tumor, with the epithelioid type occurring more frequently. Several biomarkers have been suggested for screening and early diagnosis of MPM. Currently, high levels of soluble mesothelin-related peptides (SMRP), plasma osteopontin (pOPN) and vimentin have been reported in patients with MPM as promising markers for diagnosis, but their clinical use in monitoring is still discussed. The aim of our study was to evaluate the usefulness of these substances as markers of the clinical response to treatment in patients suffering from epithelioid mesothelioma., Methods: 219 serum samples from 56 patients were collected during follow-up and the clinical response to therapy was recorded. Percentage differences between 2 consecutive measurements of SMRP, osteopontin and vimentin (Δ markers) by means of commercially available kits were correlated with changes in the clinical course., Results: Δ SMRP, Δ pOPN and Δ vimentin showed statistically significant differences between the disease categories stable disease, partial response and disease progression (p = 0.0001, p = 0.035 and p = 0.0025 for SMRP, pOPN and vimentin, respectively). Moreover, contingency table analysis showed statistically significant differences between clinical response and Δ of each marker clustered into 3 groups (<-20%, between -20% and +20%, >+20%)., Conclusions: The time course of Δ SMRP and Δ vimentin was strongly associated with disease status, and so was the time course of pOPN, albeit to a lesser extent. These markers appear to be particularly effective in cases of partial response and disease progression, while their possible use in stable disease should be better investigated.
- Published
- 2017
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27. A Novel Panel of Serum Biomarkers for MPM Diagnosis.
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Bonotti A, Foddis R, Landi S, Melaiu O, De Santi C, Giusti L, Donadio E, Ciregia F, Mazzoni MR, Lucacchini A, Bovenzi M, Comar M, Pantani E, Pistelli A, and Cristaudo A
- Subjects
- Aged, Blood Proteins metabolism, Case-Control Studies, Female, Humans, Male, Mesothelioma, Malignant, Middle Aged, Proteome metabolism, Biomarkers, Tumor blood, Lung Neoplasms blood, Mesothelioma blood
- Abstract
Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy., Competing Interests: The authors declare no competing interests.
- Published
- 2017
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28. Proteomics insight into psychiatric disorders: an update on biological fluid biomarkers.
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Giusti L, Ciregia F, Mazzoni MR, and Lucacchini A
- Abstract
Introduction: Psychiatric disorders are severe, debilitating and heterogeneous diseases with a high impact on public health. In this review we address state of the art clinical approaches to diagnose psychiatric disorders and underline the necessity to found new tools to help clinicians. Areas covered: We provide an update on proteomic studies and suggest potential biomarkers focusing on schizophrenia (SCZ), bipolar disorder (BD), and major depression (MD). In particular, we direct our attention to proteomic results obtained from studies on biological fluids. We also show an interaction analysis of differentially expressed proteins found in SCZ, BD and MD. Expert commentary: To date, there is a need to find molecular biomarkers for psychiatric disorders. The use of a proteomic approach allows protein fingerprints to be defined in normal and pathological states. We believe that saliva is an intriguing biological fluid, whose proteomic study in psychiatric disorders is still in its early stages.
- Published
- 2016
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29. Proteomic analysis of fine-needle aspiration in differential diagnosis of thyroid nodules.
- Author
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Ciregia F, Giusti L, Molinaro A, Niccolai F, Mazzoni MR, Rago T, Tonacchera M, Vitti P, Giannaccini G, and Lucacchini A
- Subjects
- Antibodies metabolism, Biomarkers blood, Biopsy, Fine-Needle, Blotting, Western, Case-Control Studies, Demography, Diagnosis, Differential, Electrophoresis, Gel, Two-Dimensional, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, ROC Curve, Reproducibility of Results, Saliva metabolism, Sensitivity and Specificity, Proteomics methods, Thyroid Gland metabolism, Thyroid Gland pathology, Thyroid Nodule diagnosis, Thyroid Nodule pathology
- Abstract
Thyroid nodules are common in the general population and vary widely in their propensity to harbor thyroid malignancies. The category of follicular lesion of undetermined significance, for instance, carries only a 15% risk of malignancy. The overarching aim of this work was the proteomic study of thyroid cancer because more effort needs to be placed on differentiating malignant thyroid nodules to avoid unnecessary thyroidectomy. We used 2-dimensional electrophoresis coupled to nano-liquid chromatography electrospray ionization tandem mass spectrometry, to examine fine-needle aspiration (FNA), which was easily attainable from the wash of the syringe used for classical FNA biopsy. Overall, we found 25 different proteins able to discriminate benign from malignant samples. The different expression of moesin; annexin A1 (ANXA1); cornulin (CRNN); lactate dehydrogenase; enolase; protein DJ-1; and superoxide dismutase was confirmed in FNA by enzyme-linked immunosorbent assay or Western blot. Receiver operating characteristic curves were calculated to investigate the discriminative power of our marker. The best performance in diagnosis was obtained by combining ANXA1, enolase, protein DJ-1, superoxide dismutase, and CRNN. In addition, the most highly ranked proteins, from the perspective of follicular lesion of undetermined significance, were ANXA1 and CRNN. The research of these candidate biomarkers has then been widened to other biological fluids, such as serum and whole saliva. In conclusion, we believe that when a decision by a thyroid nodule biopsy cannot be distinctly made, the combination of our biomarkers may be one of the criteria to be taken into account for the final decision, together with the identification of ANXA1 in serum and saliva., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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30. Bottom-up proteomics suggests an association between differential expression of mitochondrial proteins and chronic fatigue syndrome.
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Ciregia F, Kollipara L, Giusti L, Zahedi RP, Giacomelli C, Mazzoni MR, Giannaccini G, Scarpellini P, Urbani A, Sickmann A, Lucacchini A, and Bazzichi L
- Abstract
Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by unexplained fatigue not improved by rest. An area of investigation is the likely connection of CFS with defective mitochondrial function. In a previous work, we investigated the proteomic salivary profile in a couple of monozygotic twins discordant for CFS. Following this work, we analyzed mitochondrial proteins in the same couple of twins. Nano-liquid chromatography electrospray ionization mass spectrometry (nano-LC-MS) was used to study the mitochondria extracted from platelets of the twins. Subsequently, we selected three proteins that were validated using western blot analysis in a big cohort of subjects (n=45 CFS; n=45 healthy), using whole saliva (WS). The selected proteins were as follows: aconitate hydratase (ACON), ATP synthase subunit beta (ATPB) and malate dehydrogenase (MDHM). Results for ATPB and ACON confirmed their upregulation in CFS. However, the MDHM alteration was not confirmed. Thereafter, seeing the great variability of clinical features of CFS patients, we decided to analyze the expression of our proteins after splitting patients according to clinical parameters. For each marker, the values were actually higher in the group of patients who had clinical features similar to the ill twin. In conclusion, these results suggest that our potential markers could be one of the criteria to be taken into account for helping in diagnosis. Furthermore, the identification of biomarkers present in particular subgroups of CFS patients may help in shedding light upon the complex entity of CFS. Moreover, it could help in developing tailored treatments.
- Published
- 2016
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31. Salivary psoriasin (S100A7) correlates with diffusion capacity of carbon monoxide in a large cohort of systemic sclerosis patients.
- Author
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Giusti L, Sernissi F, Donadio E, Ciregia F, Giacomelli C, Giannaccini G, Mazzoni MR, Lucacchini A, and Bazzichi L
- Subjects
- Case-Control Studies, Cohort Studies, Diffusion, Female, Humans, Male, Middle Aged, ROC Curve, S100 Calcium Binding Protein A7, Carbon Monoxide metabolism, S100 Proteins metabolism, Saliva metabolism, Scleroderma, Systemic metabolism
- Abstract
Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive fibrosis of the skin and the internal organs. In a previous work we suggested a correlation between levels of salivary psoriasin (S100A7) and pulmonary involvement in SSc patients. The goals of this study are to determine the distribution characteristics of psoriasin in whole saliva (WS) of SSc and healthy donor populations and define its predictive value on diffusion capacity of carbon monoxide (DLCO), along with others clinical parameters., Methods: Salivary level of psoriasin was determined by ELISA kit in 134 SSc patients, 63 Raynaud syndrome patients, 40 patients affected by other connective diseases (non-case) and 74 healthy control subjects., Results: A significant increase of salivary psoriasin was observed in SSc patients when compared with other healthy and pathological controls. Moreover, we confirmed the efficacy of salivary psoriasin to correlate with DLCO in a large cohort of SSc patients., Conclusions: Overall our results suggest a rapid, non invasive and low costing method which can help clinicians in the evaluation of SSc pulmonary involvement.
- Published
- 2016
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32. Comparative proteomic analysis of malignant pleural mesothelioma: Focusing on the biphasic subtype.
- Author
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Giusti L, Ciregia F, Bonotti A, Da Valle Y, Donadio E, Boldrini C, Foddis R, Giannaccini G, Mazzoni MR, Canessa PA, Cristaudo A, and Lucacchini A
- Abstract
Malignant pleural mesothelioma (MPM) is a rare cancer originated from pleural mesothelial cells. MPM has been associated with long-term exposure to asbestos. In this work we performed a comparative proteomic analysis of biphasic pleural mesothelioma (B-PM). Tissue biopsies were obtained from 61 patients who were subjected to a diagnostic thoracoscopy. 2D/MS based approach was used for proteomic analysis. The 22 proteins found differentially expressed in B-PM, with respect to benign, were analyzed by Ingenuity Pathways Analysis and compared with those obtained for epitheliod pleural mesothelioma (E-PM). A different activation of transcription factors, proteins and cytokines were observed between two subtypes.
- Published
- 2016
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33. Altered protease-activated receptor-1 expression and signaling in a malignant pleural mesothelioma cell line, NCI-H28, with homozygous deletion of the β-catenin gene.
- Author
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Fazzini A, D'Antongiovanni V, Giusti L, Da Valle Y, Ciregia F, Piano I, Caputo A, D'Ursi AM, Gargini C, Lucacchini A, and Mazzoni MR
- Subjects
- Cell Line, Tumor, Cell Membrane metabolism, Cell Proliferation drug effects, Gene Expression, Gene Expression Regulation, Neoplastic, Homozygote, Humans, Intracellular Space metabolism, Mesothelioma, Malignant, Protein Transport, Receptor, PAR-1 agonists, Signal Transduction, Gene Deletion, Lung Neoplasms genetics, Lung Neoplasms metabolism, Mesothelioma genetics, Mesothelioma metabolism, Pleural Neoplasms genetics, Pleural Neoplasms metabolism, Receptor, PAR-1 genetics, Receptor, PAR-1 metabolism, beta Catenin genetics
- Abstract
Protease activated receptors (PARs) are G-protein coupled receptors that are activated by an unique proteolytic mechanism. These receptors play crucial roles in hemostasis and thrombosis but also in inflammation and vascular development. PARs have also been implicated in tumor progression, invasion and metastasis. In this study, we investigated expression and signaling of PAR1 in nonmalignant pleural mesothelial (Met-5A) and malignant pleural mesothelioma (NCI-H28) cells. We found that the expression level of PAR1 was markedly higher in NCI-H28 cells compared to Met-5A and human primary mesothelial cells. Other three malignant pleural mesothelioma cell lines, i.e. REN, Ist-Mes2, and Mero-14, did not show any significant PAR1 over-expression compared to Met-5A cell line. Thrombin and PAR1 activating peptides enhanced Met-5A and NCI-H28 cell proliferation but in NCI-H28 cells higher thrombin concentrations were required to obtain the same proliferation increase. Similarly, thrombin caused extracellular signal-regulated kinase 1/2 activation in both cell lines but NCI-H28 cells responded at higher agonist concentrations. We also determined that PAR1 signaling through Gq and G12/13 proteins is severely altered in NCI-H28 cells compared to Met-5A cells. On the contrary, PAR1 signaling through Gi proteins was persistently maintained in NCI-H28 cells. Furthermore, we demonstrated a reduction of cell surface PAR1 expression in NCI-H28 and malignant pleural mesothelioma REN cells. Thus, our results provide evidences for dysfunctional PAR1 signaling in NCI-H28 cells together with reduced plasma membrane localization. The role of PAR1 in mesothelioma progression is just emerging and our observations can promote further investigations focused on this G-protein coupled receptor.
- Published
- 2014
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34. Identifying bias in CCR1 antagonists using radiolabelled binding, receptor internalization, β-arrestin translocation and chemotaxis assays.
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Gilchrist A, Gauntner TD, Fazzini A, Alley KM, Pyen DS, Ahn J, Ha SJ, Willett A, Sansom SE, Yarfi JL, Bachovchin KA, Mazzoni MR, and Merritt JR
- Subjects
- Animals, Arrestins metabolism, CHO Cells, Cell Line, Tumor, Chemokine CCL3 metabolism, Chemotaxis, Cricetulus, HEK293 Cells, Humans, Multiple Myeloma, Phenylurea Compounds pharmacology, Piperidines pharmacology, Quinoxalines pharmacology, Radioligand Assay, Spiro Compounds pharmacology, beta-Arrestins, Receptors, CCR1 antagonists & inhibitors, Receptors, CCR1 metabolism
- Abstract
Background and Purpose: Investigators have suggested that the chemokine receptor CCR1 plays a role in multiple myeloma. Studies using antisense and neutralizing antibodies to CCR1 showed that down-regulation of the receptor altered disease progression in a mouse model. More recently, experiments utilizing scid mice injected with human myeloma cells demonstrated that the CCR1 antagonist BX471 reduced osteolytic lesions, while the CCR1 antagonist MLN-3897 prevented myeloma cell adhesion to osteoclasts. However, information is limited regarding the pharmacology of CCR1 antagonists in myeloma cells., Experimental Approach: We compared several well-studied CCR1 antagonists including AZD4818, BX471, CCX354, CP-481715, MLN-3897 and PS899877 for their ability to inhibit binding of [(125)I]-CCL3 in vitro using membranes prepared from RPMI 8226 cells, a human multiple myeloma cell line that endogenously expresses CCR1. In addition, antagonists were assessed for their ability to modulate CCL3-mediated internalization of CCR1 and CCL3-mediated cell migration using RPMI 8226 cells. As many GPCRs signal through β-arrestin-dependent pathways that are separate and distinct from those driven by G-proteins, we also evaluated the compounds for their ability to alter β-arrestin translocation., Key Results: There were clear differences between the CCR1 antagonists in their ability to inhibit CCL3 binding to myeloma cells, as well as in their ability to inhibit G-protein-dependent and -independent functional responses., Conclusions and Implications: Our studies demonstrate that tissue phenotype seems to be relevant with regards to CCR1. Moreover, it appears that for CCR1 antagonists, inhibition of β-arrestin translocation is not necessarily linked to chemotaxis or receptor internalization., (© 2014 The British Pharmacological Society.)
- Published
- 2014
- Full Text
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