112 results on '"Dechecchi, Maria Cristina"'
Search Results
2. Sphingolipids and plasma membrane hydrolases in human primary bronchial cells during differentiation and their altered patterns in cystic fibrosis
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Loberto, Nicoletta, Mancini, Giulia, Bassi, Rosaria, Carsana, Emma Veronica, Tamanini, Anna, Pedemonte, Nicoletta, Dechecchi, Maria Cristina, Sonnino, Sandro, and Aureli, Massimo
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- 2020
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3. Exploring the effect of chirality on the therapeutic potential of N-alkyl-deoxyiminosugars: anti-inflammatory response to Pseudomonas aeruginosa infections for application in CF lung disease
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De Fenza, Maria, D'Alonzo, Daniele, Esposito, Anna, Munari, Silvia, Loberto, Nicoletta, Santangelo, Alessandra, Lampronti, Ilaria, Tamanini, Anna, Rossi, Alice, Ranucci, Serena, De Fino, Ida, Bragonzi, Alessandra, Aureli, Massimo, Bassi, Rosaria, Tironi, Matteo, Lippi, Giuseppe, Gambari, Roberto, Cabrini, Giulio, Palumbo, Giovanni, Dechecchi, Maria Cristina, and Guaragna, Annalisa
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- 2019
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4. A microRNA signature from serum exosomes of patients with glioma as complementary diagnostic biomarker
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Santangelo, Alessandra, Imbrucè, Pietro, Gardenghi, Beatrice, Belli, Laura, Agushi, Rina, Tamanini, Anna, Munari, Silvia, Bossi, Alessandra Maria, Scambi, Ilaria, Benati, Donatella, Mariotti, Raffaella, Di Gennaro, Gianfranco, Sbarbati, Andrea, Eccher, Albino, Ricciardi, Giuseppe Kenneth, Ciceri, Elisa Maria, Sala, Francesco, Pinna, Giampietro, Lippi, Giuseppe, Cabrini, Giulio, and Dechecchi, Maria Cristina
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- 2017
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5. β-sitosterol ameliorates inflammation and Pseudomonas aeruginosa lung infection in a mouse model
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Rossi, Alice, Bragonzi, Alessandra, Medede, Melessike, De Fino, Ida, Lippi, Giuseppe, Prosdocimi, Marco, Tamanini, Anna, Cabrini, Giulio, and Dechecchi, Maria Cristina
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- 2023
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6. New TMA (4,6,4′-Trimethyl angelicin) Analogues as Anti-Inflammatory Agents in the Treatment of Cystic Fibrosis Lung Disease.
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Tupini, Chiara, Chilin, Adriana, Rossi, Alice, De Fino, Ida, Bragonzi, Alessandra, D'Aversa, Elisabetta, Cosenza, Lucia Carmela, Vaccarin, Christian, Sacchetti, Gianni, Borgatti, Monica, Tamanini, Anna, Dechecchi, Maria Cristina, Sanvito, Francesca, Gambari, Roberto, Cabrini, Giulio, and Lampronti, Ilaria
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LUNGS ,CYSTIC fibrosis ,PULMONARY fibrosis ,LUNG diseases ,ANTI-inflammatory agents ,CYSTIC fibrosis transmembrane conductance regulator ,LUTEINIZING hormone releasing hormone - Abstract
A series of new-generation TMA (4,6,4′-trimethyl angelicin) analogues was projected and synthetized in order to ameliorate anti-inflammatory activity, with reduced or absent toxicity. Since the NF-κB transcription factor (TF) plays a critical role in the expression of IL-8 (Interluekin 8), a typical marker of lung inflammation in Cystic Fibrosis (CF), the use of agents able to interfere with the NF-κB pathway represents an interesting therapeutic strategy. Through preliminary EMSA experiments, we identified several new TMA derivatives able to inhibit the NF-κB/DNA complex. The selected active molecules were then analyzed to evaluate the anti-inflammatory effect using both Pseudomonas aeruginosa (PAO1) infection and TNF-alpha stimulus on the CF IB3-1 cell line. It was demonstrated that mainly two TMA analogues, GY971a mesylate salt (6-p-minophenyl-4,4′-dimethyl-angelicin) and GY964 (4-phenyl-6,4′-dimethyl-angelicin), were able to decrease the IL-8 gene expression. At the same time, these molecules were found to have no pro-apoptotic, mutagenic and phototoxic effects, facilitating our decision to test the efficacy in vivo by using a mouse model of acute P. aeruginosa lung infection. The anti-inflammatory effect of GY971a was confirmed in vivo; this derivative was able to deeply decrease the total number of inflammatory cells, the neutrophil count and the cytokine/chemokine profile in the P. aeruginosa acute infection model, without evident toxicity. Considering all the obtained and reported in vitro and in vivo pre-clinical results, GY971a seems to have interesting anti-inflammatory effects, modulating the NF-κB pathway, as well as the starting lead compound TMA, but without side effects. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Improved Trimethylangelicin Analogs for Cystic Fibrosis: Design, Synthesis and Preliminary Screening.
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Vaccarin, Christian, Gabbia, Daniela, Franceschinis, Erica, De Martin, Sara, Roverso, Marco, Bogialli, Sara, Sacchetti, Gianni, Tupini, Chiara, Lampronti, Ilaria, Gambari, Roberto, Cabrini, Giulio, Dechecchi, Maria Cristina, Tamanini, Anna, Marzaro, Giovanni, and Chilin, Adriana
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CYSTIC fibrosis ,CHEMICAL synthesis ,PHOTOCHEMISTRY ,MUTAGENS - Abstract
A small library of new angelicin derivatives was designed and synthesized with the aim of bypassing the side effects of trimethylangelicin (TMA), a promising agent for the treatment of cystic fibrosis. To prevent photoreactions with DNA, hindered substituents were inserted at the 4 and/or 6 positions. Unlike the parent TMA, none of the new derivatives exhibited significant cytotoxicity or mutagenic effects. Among the synthesized compounds, the 4-phenylderivative 12 and the 6-phenylderivative 25 exerted a promising F508del CFTR rescue ability. On these compounds, preliminary in vivo pharmacokinetic (PK) studies were carried out, evidencing a favorable PK profile per se or after incorporation into lipid formulations. Therefore, the selected compounds are good candidates for future extensive investigation to evaluate and develop novel CFTR correctors based on the angelicin structure. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Serum Exosomal microRNA-21, 222 and 124-3p as Noninvasive Predictive Biomarkers in Newly Diagnosed High-Grade Gliomas: A Prospective Study
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Olioso, Debora, Caccese, Mario, Santangelo, Alessandra, Lippi, Giuseppe, Zagonel, Vittorina, Cabrini, Giulio, Lombardi, Giuseppe, and Dechecchi, Maria Cristina
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Exosom, microRNA, Biomarkers, Glioma ,microRNA ,liquid biopsy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,circulating miRNAs ,Exosom ,Glioma ,exosomes ,Biomarkers ,RC254-282 ,Article ,high-grade glioma - Abstract
Background: High-grade gliomas (HGG) are malignant brain tumors associated with frequent recurrent disease. Clinical management of HGG patients is currently devoid of blood biomarkers for early diagnosis, monitoring therapeutic effects and predicting recurrence. Different circulating miRNAs, both free and associated with exosomes, are described in patients with HGG. We previously identified miR-21, miR-222 and miR-124-3p purified from serum exosomes as molecular signature to help pre-operative clinical diagnosis and grading of gliomas. The aim of the present study was to verify this signature as a tool to assess the effect of treatment and for the early identification of progression in newly diagnosed HGG patients. Material and Methods: Major inclusion criteria were newly diagnosed, histologically confirmed HGG patients, no prior chemotherapy, ECOG PS 0-2 and patients scheduled for radiochemotherapy with temozolomide as first-line treatment after surgery. RANO criteria were used for response assessment. Serum was collected at baseline and subsequently at each neuroradiological assessment. mir-21, -222 and -124-3p expression in serum exosomes was measured in all samples. Results: A total number of 57 patients were enrolled, 41 were male, 52 with glioblastoma and 5 with anaplastic astrocytoma, 18 received radical surgery. HGG patients with higher exosomal miRNA expression displayed a statistically significant lower progression-free survival and overall survival. Increased expression of miR-21, -222 and -124-3p during post-operative follow-up was associated with HGG progression. Conclusions: These data indicate that miR-21, -222 and -124-3p in serum exosomes may be useful molecular biomarkers for complementing clinical evaluation of early tumor progression during post-surgical therapy in patients with HGG.
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- 2021
9. Regulation of expression of O6-methylguanine-DNA methyltransferase and the treatment of glioblastoma (Review)
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CABRINI, GIULIO, FABBRI, ENRICA, NIGRO, CRISTIANA LO, DECHECCHI, MARIA CRISTINA, and GAMBARI, ROBERTO
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- 2015
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10. miRNAs in Serum Exosomes for Differential Diagnosis of Brain Metastases.
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Catelan, Silvia, Olioso, Debora, Santangelo, Alessandra, Scapoli, Chiara, Tamanini, Anna, Pinna, Giampietro, Sala, Francesco, Lippi, Giuseppe, Nicolato, Antonio, Cabrini, Giulio, and Dechecchi, Maria Cristina
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BRAIN tumor diagnosis ,KRUSKAL-Wallis Test ,STATISTICS ,EXOSOMES ,CONFIDENCE intervals ,SERUM ,MELANOMA ,NEUROSURGERY ,GLIOMAS ,METASTASIS ,DIFFERENTIAL diagnosis ,MICRORNA ,LUNG tumors ,CASE-control method ,BLOOD collection ,CANCER patients ,DESCRIPTIVE statistics ,KIDNEY tumors ,TUMOR markers ,RADIOSURGERY ,RECEIVER operating characteristic curves ,SENSITIVITY & specificity (Statistics) ,DATA analysis ,DATA analysis software ,BREAST tumors - Abstract
Simple Summary: Current methods for the detection of brain malignancies often display low sensitivity and specificity. Noninvasive biomarkers can complement imaging techniques to improve the diagnosis of these tumors. The aim of this study was to identify circulating miRNAs in serum exosomes useful in all phases of the diagnostic and therapeutic path of patients with malignant brain lesions. Our data show a signature of exosomal miRNAs useful for the differential diagnosis of brain metastases and for monitoring tumor evolution over time. Circulating miRNAs are increasingly studied and proposed as tumor markers with the aim of investigating their role in monitoring the response to therapy as well as the natural evolution of primary or secondary brain tumors. This study aimed to evaluate the modulation of the expression of three miRNAs, miR-21, miR-222 and miR-124-3p, in the serum exosomes of patients with high-grade gliomas (HGGs) and brain metastases (BMs) to verify their usefulness in the differential diagnosis of brain masses; then, it focused on their variations following the surgical and/or radiosurgical treatment of the BMs. A total of 105 patients with BMs from primary lung or breast cancer, or melanoma underwent neurosurgery or radiosurgery treatment, and 91 patients with HGGs were enrolled, along with 30 healthy controls. A significant increase in miR-21 expression in serum exosomes was observed in both HGGs and BMs compared with healthy controls; on the other hand, miR-124-3p was significantly decreased in BMs, and it was increased in HGGs. After the surgical or radiosurgical treatment of patients with BMs, a significant reduction in miR-21 was noted with both types of treatments. This study identified a signature of exosomal miRNAs that could be useful as a noninvasive complementary analysis both in the differential diagnosis of BMs from glial tumors and in providing information on tumor evolution over time. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Anti-inflammatory effect of miglustat in bronchial epithelial cells
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Dechecchi, Maria Cristina, Nicolis, Elena, Norez, Caroline, Bezzerri, Valentino, Borgatti, Monica, Mancini, Irene, Rizzotti, Paolo, Ribeiro, Carla M.P., Gambari, Roberto, Becq, Frederic, and Cabrini, Giulio
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- 2008
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12. Expression of microRNA-93 and Interleukin-8 during Pseudomonas aeruginosa-Mediated Induction of Proinflammatory Responses
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Fabbri, Enrica, Borgatti, Monica, Montagner, Giulia, Bianchi, Nicoletta, Finotti, Alessia, Lampronti, Ilaria, Bezzerri, Valentino, Dechecchi, Maria Cristina, Cabrini, Giulio, and Gambari, Roberto
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- 2014
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13. Modulators of Sphingolipid Metabolism Reduce Lung Inflammation
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Dechecchi, Maria Cristina, Nicolis, Elena, Mazzi, Paola, Cioffi, Federica, Bezzerri, Valentino, Lampronti, Ilaria, Huang, Song, Wiszniewski, Ludovic, Gambari, Roberto, Scupoli, Maria Teresa, Berton, Giorgio, and Cabrini, Giulio
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- 2011
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14. Decoy oligodeoxyribonucleotides and peptide nucleic acids-DNA chimeras targeting nuclear factor kappa-B: Inhibition of IL-8 gene expression in cystic fibrosis cells infected with Pseudomonas aeruginosa
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Gambari, Roberto, Borgatti, Monica, Bezzerri, Valentino, Nicolis, Elena, Lampronti, Ilaria, Dechecchi, Maria Cristina, Mancini, Irene, Tamanini, Anna, and Cabrini, Giulio
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- 2010
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15. Pyrogallol, an active compound from the medicinal plant Emblica officinalis, regulates expression of pro-inflammatory genes in bronchial epithelial cells
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Nicolis, Elena, Lampronti, Ilaria, Dechecchi, Maria Cristina, Borgatti, Monica, Tamanini, Anna, Bianchi, Nicoletta, Bezzerri, Valentino, Mancini, Irene, Grazia Giri, Maria, Rizzotti, Paolo, Gambari, Roberto, and Cabrini, Giulio
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- 2008
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16. Transcription Factor Oligodeoxynucleotides to NF-κB Inhibit Transcription of IL-8 in Bronchial Cells
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Bezzerri, Valentino, Borgatti, Monica, Nicolis, Elena, Lampronti, Ilaria, Dechecchi, Maria Cristina, Mancini, Irene, Rizzotti, Paolo, Gambari, Roberto, and Cabrini, Giulio
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- 2008
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17. MPB-07 Reduces the Inflammatory Response to Pseudomonas aeruginosa in Cystic Fibrosis Bronchial Cells
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Dechecchi, Maria Cristina, Nicolis, Elena, Bezzerri, Valentino, Vella, Antonio, Colombatti, Marco, Assael, Baroukh Maurice, Mettey, Yvette, Borgatti, Monica, Mancini, Irene, Gambari, Roberto, Becq, Frederic, and Cabrini, Giulio
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- 2007
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18. Design, synthesis and biological evaluation of novel trimethylangelicin analogues targeting nuclear factor kB (NF-kB)
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Marzaro, Giovanni, Lampronti, Ilaria, D'Aversa, Elisabetta, Sacchetti, Gianni, Miolo, Giorgia, Vaccarin, Christian, Cabrini, Giulio, Dechecchi, Maria Cristina, Gambari, Roberto, and Chilin, Adriana
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- 2018
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19. PLCB3 Loss-of-function Reduces P. aeruginosa-dependent IL-8 Release in Cystic Fibrosis
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Rimessi, Alessandro, Bezzerri, Valentino, Salvatori, Francesca, Tamanini, Anna, Nigro, Federica, Dechecchi, Maria Cristina, Santangelo, Alessandra, Prandini, Paola, Munari, Silvia, Provezza, Lisa, Garreau de Loubresse, Nicolas, Muller, Jean, Ribeiro, Carla M P, Lippi, Giuseppe, Gambari, Roberto, Pinton, Paolo, and Cabrini, Giulio
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IL-8 ,Phospholipase C Beta 3 ,airway inflammation ,calcium signaling ,cystic fibrosis - Published
- 2018
20. A molecular signature associated with prolonged survival in glioblastoma patients treated with regorafenib.
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Santangelo, Alessandra, Rossato, Marzia, Lombardi, Giuseppe, Benfatto, Salvatore, Lavezzari, Denise, Salvo, Gian Luca De, Indraccolo, Stefano, Dechecchi, Maria Cristina, Prandini, Paola, Gambari, Roberto, Scapoli, Chiara, Gennaro, Gianfranco Di, Caccese, Mario, Eoli, Marica, Rudà, Roberta, Brandes, Alba Ariela, Ibrahim, Toni, Rizzato, Simona, Lolli, Ivan, and Lippi, Giuseppe
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- 2021
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21. Heparan Sulfate Glycosaminoglycans Are Involved in Adenovirus Type 5 and 2-Host Cell Interactions
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Dechecchi, Maria Cristina, Tamanini, Anna, Bonizzato, Alberto, and Cabrini, Giulio
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- 2000
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22. Targeting miR-155-5p and miR-221-3p by peptide nucleic acids induces caspase-3 activation and apoptosis in temozolomide-resistant T98G glioma cells.
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Milani, Roberta, Brognara, Eleonora, Fabbri, Enrica, Manicardi, Alex, Corradini, Roberto, Finotti, Alessia, Gasparello, Jessica, Borgatti, Monica, Cosenza, Lucia Carmela, Lampronti, Ilaria, Dechecchi, Maria Cristina, Cabrini, Giulio, and Gambari, Roberto
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- 2019
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23. Sphingolipids role in the regulation of inflammatory response: From leukocyte biology to bacterial infection.
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Chiricozzi, Elena, Loberto, Nicoletta, Schiumarini, Domitilla, Samarani, Maura, Mancini, Giulia, Tamanini, Anna, Lippi, Giuseppe, Dechecchi, Maria Cristina, Bassi, Rosaria, Giussani, Paola, and Aureli, Massimo
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BACTERIOLOGY ,SPHINGOLIPIDS ,BACTERIAL diseases ,LEUCOCYTES ,CELL physiology - Abstract
Abstract: Sphingolipids (SLs) are amphiphilic molecules mainly associated with the external leaflet of eukaryotic plasma membrane, and are structural membrane components with key signaling properties. Since the beginning of the last century, a large number of papers described the involvement of these molecules in several aspects of cell physiology and pathology. Several lines of evidence support the critical role of SLs in inflammatory diseases, by acting as anti‐ or pro‐inflammatory mediators. They are involved in control of leukocyte activation and migration, and are recognized as essential players in host response to pathogenic infection. We propose here a critical overview of current knowledge on involvement of different classes of SLs in inflammation, focusing on the role of simple and complex SLs in pathogen‐mediated inflammatory response. [ABSTRACT FROM AUTHOR]
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- 2018
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24. A Peptide Nucleic Acid against MicroRNA miR-145-5p Enhances the Expression of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Calu-3 Cells.
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Fabbri, Enrica, Tamanini, Anna, Jakova, Tiziana, Gasparello, Jessica, Manicardi, Alex, Corradini, Roberto, Sabbioni, Giuseppe, Finotti, Alessia, Borgatti, Monica, Lampronti, Ilaria, Munari, Silvia, Dechecchi, Maria Cristina, Cabrini, Giulio, and Gambari, Roberto
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PEPTIDE nucleic acids ,MICRORNA ,GENE expression ,CYSTIC fibrosis transmembrane conductance regulator ,AIR pollutants - Abstract
Peptide nucleic acids (PNAs) are very useful tools for gene regulation at different levels, but in particular in the last years their use for targeting microRNA (anti-miR PNAs) has provided impressive advancements. In this respect, microRNAs related to the repression of cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is defective in cystic fibrosis, are of great importance in the development of new type of treatments. In this paper we propose the use of an anti-miR PNA for targeting miR-145, a microRNA reported to suppress CFTR expression. Octaarginine-anti-miR PNA conjugates were delivered to Calu-3 cells, exerting sequence dependent targeting of miR-145-5p. This allowed to enhance expression of the miR-145 regulated CFTR gene, analyzed at mRNA (RT-qPCR, Reverse Transcription quantitative Polymerase Chain Reaction) and CFTR protein (Western blotting) level. [ABSTRACT FROM AUTHOR]
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- 2018
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25. Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial Cells.
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Schiumarini, Domitilla, Loberto, Nicoletta, Mancini, Giulia, Bassi, Rosaria, Giussani, Paola, Chiricozzi, Elena, Samarani, Maura, Munari, Silvia, Tamanini, Anna, Cabrini, Giulio, Lippi, Giuseppe, Dechecchi, Maria Cristina, Sonnino, Sandro, and Aureli, Massimo
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LIPID rafts ,PSEUDOMONAS aeruginosa infections ,CELL membranes ,SPHINGOLIPIDS ,HYDROLASES ,CYSTIC fibrosis ,EPITHELIAL cells - Abstract
Cystic fibrosis (CF) is the most common autosomal genetic recessive disease caused by mutations of gene encoding for the cystic fibrosis transmembrane conductance regulator. Patients with CF display a wide spectrum of symptoms, the most severe being chronic lung infection and inflammation, which lead to onset of cystic fibrosis lung disease. Several studies indicate that sphingolipids play a regulatory role in airway inflammation. The inhibition and downregulation of GBA2, the enzyme catabolizing glucosylceramide to ceramide, are associated with a significant reduction of IL-8 production in CF bronchial epithelial cells. Herein, we demonstrate that GBA2 plays a role in the proinflammatory state characterizing CF cells. We also report for the first time that Pseudomonas aeruginosa infection causes a recruitment of plasma membrane-associated glycosphingolipid hydrolases into lipid rafts of CuFi-1-infected cells. This reorganization of cell membrane may be responsible for activation of a signaling cascade, culminating in aberrant inflammatory response in CF bronchial epithelial cells upon bacterial infection. Taken together, the presented data further support the role of sphingolipids and their metabolic enzymes in controlling the inflammatory response in CF. [ABSTRACT FROM AUTHOR]
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- 2017
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26. MPB-07 Reduces the Inflammatory Response to Pseudomonas aeruginosa in CF Bronchial Cells
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Dechecchi, Maria Cristina, Nicolis, Elena, Bezzerri, Valentino, Vella, Antonio, Colombatti, Marco, Assael, Baroukh Maurice, Mettey, Yvette, Borgatti, Monica, Mancini, Irene, Gambari, Roberto, Becq, Frédéric, Cabrini, Giulio, Laboratory of Molecular Pathology, University Hospital of Verona, Laboratory of Clinical Immunology, University of Verona (UNIVR), Department of Pathology, Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry an Molecular Biology, Università degli Studi di Ferrara (UniFE), and Vaincre la Mucoviscidose
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cystic fibrosis • inflammation • Pseudomonas aeruginosa ,[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,respiratory system ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,respiratory tract diseases - Abstract
(IF : 4,608); International audience; Chronic lung inflammation in cystic fibrosis (CF) is specifically characterized by predominant endobronchial neutrophil infiltrates, colonization by Pseudomonas aeruginosa, and elevated levels of cytokines and chemokines, first of all IL-8. The extensive inflammatory process in CF lungs is the basis of progressive tissue damage and is largely considered detrimental, making antiinflammatory approaches a relevant therapeutic target. This neutrophil-dominated inflammation seems to be related to an excessive proinflammatory signaling, originating from the same surface epithelial cells expressing the defective CF transmembrane conductance regulator (CFTR) protein, although the underlying mechanisms have not been completely elucidated. To investigate the relationship between defective CFTR and the inflammatory response to P. aeruginosa in CF airway cells, we studied the effect of the DeltaF508 CFTR corrector, benzo(c)quinolizinium (MPB)-07 (Dormer et al., J Cell Science 2001;114:4073-4081). CF bronchial epithelial IB3-1 and CuFi-1 cells overproduced the inflammatory molecules, IL-8 and intercellular adhesion molecule (ICAM)-1, in response to P. aeruginosa, compared with the wild-type, CFTR-expressing bronchial cells, S9, and NuLi-1 cells. In both IB3-1 and CuFi-1 cells, the corrector MPB-07 dramatically reduces the IL-8 and ICAM-1 mRNA expression elicited by P. aeruginosa infection. Correction of CFTR-dependent Cl- efflux was confirmed in MPB-07-treated IB3-1 and CuFi-1 cells. In conclusion, the DeltaF508 CFTR corrector MPB-07 produces an antiinflammatory effect in CF bronchial cells exposed to P. aeruginosa in vitro.
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- 2007
27. Differential Effects of Angelicin Analogues on NF-κB Activity and IL-8 Gene Expression in Cystic Fibrosis IB3-1 Cells.
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Lampronti, Ilaria, Manzione, Maria Giulia, Sacchetti, Gianni, Ferrari, Davide, Spisani, Susanna, Bezzerri, Valentino, Finotti, Alessia, Borgatti, Monica, Dechecchi, Maria Cristina, Miolo, Giorgia, Marzaro, Giovanni, Cabrini, Giulio, Gambari, Roberto, and Chilin, Adriana
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GENE expression ,EPITHELIAL cells ,INTERLEUKIN-8 ,CYSTIC fibrosis ,ANTI-inflammatory agents ,PREVENTION - Abstract
The angelicin analogue 4,6,4′-trimethylangelicin (TMA) was recently reported as a strong inhibitor of nuclear factor-κB (NF-κB) activity and of the expression of the interleukin-8 (IL-8) gene in bronchial epithelial cells in which the inflammatory response has been challenged with P. aeruginosa, the most common bacterium found in the airways of patients affected by cystic fibrosis (CF). These findings encouraged us to analyze new synthetic analogues of TMA in order to evaluate their biological activities on human bronchial epithelial CF IB3-1 cells and to find more potent anti-NF-κB agents exhibiting only minor antiproliferative effects. Analogues able to inhibit NF-κB/DNA interaction at lower concentration than TMA were found and selected to investigate their biological activity on IB3-1 cells induced with TNF-α. In this biological system, NF-κB-mediated IL-8 gene expression was investigated. Some analogues showed similar activity to the lead compound TMA. Other analogues displayed higher activities; in particular, the most interesting compounds showing relevant anti-inflammatory effects were found to cause 56–83% reduction of IL-8 mRNA expression at low concentrations (1–10 μM), without changes in cell proliferation pattern, demonstrating their potential interest for a possible development of anti-inflammatory therapy of cystic fibrosis. [ABSTRACT FROM AUTHOR]
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- 2017
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28. Transient Receptor Potential Ankyrin 1 Channels Modulate Inflammatory Response in Respiratory Cells from Patients with Cystic Fibrosis.
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Prandini, Paola, De Logu, Francesco, Fusi, Camilla, Provezza, Lisa, Nassini, Romina, Montagner, Giulia, Materazzi, Serena, Munari, Silvia, Gilioli, Eliana, Bezzerri, Valentino, Finotti, Alessia, Lampronti, Ilaria, Tamanini, Anna, Dechecchi, Maria Cristina, Lippi, Giuseppe, Ribeiro, Carla M., Rimessi, Alessandro, Pinton, Paolo, Gambari, Roberto, and Geppetti, Pierangelo
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- 2016
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29. Regulation of expression of O6-methylguanine-DNA methyltransferase and the treatment of glioblastoma (Review).
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CABRINI, GIULIO, FABBRI, ENRICA, LO NIGRO, CRISTIANA, DECHECCHI, MARIA CRISTINA, and GAMBARI, ROBERTO
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- 2015
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30. Antibacterial and anti-inflammatory activity of a temporin B peptide analogue on an in vitro model of cystic fibrosis.
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Bezzerri, Valentino, Avitabile, Concetta, Dechecchi, Maria Cristina, Lampronti, Ilaria, Borgatti, Monica, Montagner, Giulia, Cabrini, Giulio, Gambari, Roberto, and Romanelli, Alessandra
- Abstract
Natural peptides with antimicrobial properties are deeply investigated as tools to fight bacteria resistant to common antibiotics. Small peptides, as those belonging to the temporin family, are very attractive because their activity can easily be tuned after small modification to their primary sequence. Structure-activity studies previously reported by us allowed the identification of one peptide, analogue of temporin B, TB_KKG6A, showing, unlike temporin B, antimicrobial activity against both Gram-positive and Gram-negative bacteria. In this paper, we investigated the antimicrobial and anti-inflammatory activity of the peptide TB_KKG6A against Pseudomonas aeruginosa. Interestingly, we found that the peptide exhibits antimicrobial activity at low concentrations, being able to downregulate the pro-inflammatory chemokines and cytokines interleukin (IL)-8, IL-1 β, IL-6 and tumor necrosis factor- α produced downstream infected human bronchial epithelial cells. Experiments were carried out also with temporin B, which was found to show pro-inflammatory activity. Details on the interaction between TB_KKG6A and the P. aeruginosa LPS were obtained by circular dichroism and fluorescence studies. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
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- 2014
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31. GBA2-Encoded β-Glucosidase Activity Is Involved in the Inflammatory Response to Pseudomonas aeruginosa.
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Loberto, Nicoletta, Tebon, Maela, Lampronti, Ilaria, Marchetti, Nicola, Aureli, Massimo, Bassi, Rosaria, Giri, Maria Grazia, Bezzerri, Valentino, Lovato, Valentina, Cantù, Cinzia, Munari, Silvia, Cheng, Seng H., Cavazzini, Alberto, Gambari, Roberto, Sonnino, Sandro, Cabrini, Giulio, and Dechecchi, Maria Cristina
- Subjects
GLUCOSIDASES ,CERAMIDASES ,PSEUDOMONAS aeruginosa ,CLINICAL medicine ,GLYCOMICS ,PEDIATRIC pulmonology - Abstract
Current anti-inflammatory strategies for the treatment of pulmonary disease in cystic fibrosis (CF) are limited; thus, there is continued interest in identifying additional molecular targets for therapeutic intervention. Given the emerging role of sphingolipids (SLs) in various respiratory disorders, including CF, drugs that selectively target the enzymes associated with SL metabolism are under development. Miglustat, a well-characterized iminosugar-based inhibitor of β-glucosidase 2 (GBA2), has shown promise in CF treatment because it reduces the inflammatory response to infection by P. aeruginosa and restores F508del-CFTR chloride channel activity. This study aimed to probe the molecular basis for the anti-inflammatory activity of miglustat by examining specifically the role of GBA2 following the infection of CF bronchial epithelial cells by P. aeruginosa. We also report the anti-inflammatory activity of another potent inhibitor of GBA2 activity, namely N-(5-adamantane-1-yl-methoxy)pentyl)-deoxynojirimycin (Genz-529648). In CF bronchial cells, inhibition of GBA2 by miglustat or Genz-529648 significantly reduced the induction of IL-8 mRNA levels and protein release following infection by P. aeruginosa. Hence, the present data demonstrate that the anti-inflammatory effects of miglustat and Genz-529648 are likely exerted through inhibition of GBA2. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
32. Effects of decoy molecules targeting NFkappaB transcription factors in cystic fibrosis IB3-1 cells.
- Author
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Finotti, Alessia, Borgatti, Monica, Bezzerri, Valentino, Nicolis, Elena, Lampronti, Ilaria, Dechecchi, Maria Cristina, Mancini, Irene, Cabrini, Giulio, Saviano, Michele, Avitabile, Concetta, Romanelli, Alessandra, and Gambari, Roberto
- Subjects
CYSTIC fibrosis ,CYTOKINES ,CHEMOKINES ,INTERLEUKIN-8 ,TRANSCRIPTION factors - Abstract
One of the clinical feature of cystic fibrosis (CF) is a deep inflammatory process, which is characterized by production and release of cytokines and chemokines, among which interleukin 8 (IL-8) represents one of the most important. Accordingly, there is a growing interest in developing therapies against CF to reduce the excessive inflammatory response in the airways of CF patients. Since transcription factor NFkappaB plays a critical role in IL-8 expression, the transcription factor decoy (TFD) strategy might be of interest. In order to demonstrate that TFD against NFkappaB interferes with the NFkappaB pathway we proved, by chromatin immunoprecipitation (ChIP) that treatment with TFD oligodeoxyribonucleotides of cystic fibrosis IB3-1 cells infected with Pseudomonas aeruginosa leads to a decrease occupancy of the Il-8 gene promoter by NFkappaB factors. In order to develop more stable therapeutic molecules, peptide nucleic acids (PNAs) based agents were considered. In this respect PNA-DNA-PNA (PDP) chimeras are molecules of great interest from several points of view: (1) they can be complexed with liposomes and microspheres; (2) they are resistant to DNases, serum and cytoplasmic extracts; (3) they are potent decoy molecules. By using electrophoretic mobility shift assay and RT-PCR analysis we have demonstrated that (1) the effects of PDP/PDP NFkappaB decoy chimera on accumulation of pro-inflammatory mRNAs in P. aeruginosa infected IB3-1 cells reproduce that of decoy oligonucleotides; in particular (2) the PDP/PDP chimera is a strong inhibitor of IL-8 gene expression; (3) the effect of PDP/PDP chimeras, unlike those of ODN-based decoys, are observed even in the absence of protection with lipofectamine. These informations are of great impact, in our opinion, for the development of stable molecules to be used in non-viral gene therapy of cystic fibrosis. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
33. Chemical conjugation of ΔF508-CFTR corrector deoxyspergualin to transporter human serum albumin enhances its ability to rescue C1-channel functions.
- Author
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Norez, Caroline, Pasetto, Matteo, Dechecchi, Maria Cristina, Barison, Erika, Anselmi, Cristina, Tamanini, Anna, Quiri, Federica, Cattel, Luigi, Rizzotti, Paolo, Dosio, Franco, Cabrini, Giulio, and Colombatti, Marco
- Subjects
CYSTIC fibrosis ,SERUM albumin ,MOLECULAR chaperones ,ENDOPLASMIC reticulum ,UBIQUITIN ,OXIDOREDUCTASES ,PHYSIOLOGICAL research - Abstract
The most common mutation of the cystic fibrosis (CF) gene, the deletion of Phe508, encodes a protein (ΔF508-CFTR) that fails to fold properly, thus mutated ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR) is recognized and degraded via the ubiquitin-proteasome endoplasmic reticulum-associated degradation pathway. Chemical and pharmacological chaperones and ligand-induced transport open options for designing specific drugs to control protein (mis)folding or transport. A class of compounds that has been proposed as having potential utility in ΔF508-CFTR is that which targets the molecular chaperone and proteasome systems. In this study, we have selected deoxyspergualin (DSG) as a reference molecule for this class of compounds and for ease of cross-linking to human serum albumin (HSA) as a protein transporter. Chemical cross-linking of DSG to HSA via a disulfide- based cross-linker and its administration to cells carrying ΔF508- CFTR resulted in a greater enhancement of ΔF508-CFTR function than when free DSG was used. Function of the selenium-dependent oxidoreductase system was required to allow intracellular activation of HSA-DSG conjugates. The principle that carrier proteins can deliver pharmacological chaperones to cells leading to correction of defective CFTR functions is therefore proven and warrants further investigations. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
34. Cationic trypsinogen and pancreatic secretory trypsin inhibitor gene mutations in neonatal hypertrypsinaemia.
- Author
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Patuzzo, Cristina, Castellani, Carlo, Sagramoso, Carlo, Gomez-Lira, Macarena, Bonamini, Deborah, Belpinati, Francesca, Dechecchi, Maria Cristina, Assael, Aroukh Maurice, and Pignatti, Pier Franco
- Subjects
NEONATAL diseases ,GENETIC mutation ,GENETICS - Abstract
Neonatal hypertrypsinaemia with normal sweat chloride detected during CF screening may be related to trypsin activation. We have looked for mutations of the cationic trypsinogen (PRSS1) and pancreatic secretory trypsin inhibitor (PSTI) genes in 50 hypertrypsinaemic neonates with known CFTR genotypes and negative sweat test. No mutations were found in either gene. Two silent polymorphisms were detected in the PRSS1 gene. A polymorphism in the promoter region and an intronic polymorphism of the PSTI gene were found. No difference was observed in the frequency of PRSS1 or PSTI polymorphisms in neonates carrying or not carrying CF mutations. These results do not provide an indication for an increased frequency of mutations in the PRSS1 and PSTI genes in this group of neonates with transient hypertrypsinaemia. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
35. Enhancing the Expression of CFTR Using Antisense Molecules against MicroRNA miR-145-5p.
- Author
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Finotti, Alessia, Gasparello, Jessica, Fabbri, Enrica, Tamanini, Anna, Corradini, Roberto, Dechecchi, Maria Cristina, Cabrini, Giulio, and Gambari, Roberto
- Published
- 2019
- Full Text
- View/download PDF
36. A Peptide-Nucleic Acid Targeting miR-335-5p Enhances Expression of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene with the Possible Involvement of the CFTR Scaffolding Protein NHERF1.
- Author
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Tamanini, Anna, Fabbri, Enrica, Jakova, Tiziana, Gasparello, Jessica, Manicardi, Alex, Corradini, Roberto, Finotti, Alessia, Borgatti, Monica, Lampronti, Ilaria, Munari, Silvia, Dechecchi, Maria Cristina, Cabrini, Giulio, Gambari, Roberto, and Blasi, Francesco B.
- Subjects
CYSTIC fibrosis transmembrane conductance regulator ,SCAFFOLD proteins ,PEPTIDE nucleic acids ,REGULATOR genes - Abstract
(1) Background: Up-regulation of the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) might be of great relevance for the development of therapeutic protocols for cystic fibrosis (CF). MicroRNAs are deeply involved in the regulation of CFTR and scaffolding proteins (such as NHERF1, NHERF2 and Ezrin). (2) Methods: Content of miRNAs and mRNAs was analyzed by RT-qPCR, while the CFTR and NHERF1 production was analyzed by Western blotting. (3) Results: The results here described show that the CFTR scaffolding protein NHERF1 can be up-regulated in bronchial epithelial Calu-3 cells by a peptide-nucleic acid (PNA) targeting miR-335-5p, predicted to bind to the 3′-UTR sequence of the NHERF1 mRNA. Treatment of Calu-3 cells with this PNA (R8-PNA-a335) causes also up-regulation of CFTR. (4) Conclusions: We propose miR-335-5p targeting as a strategy to increase CFTR. While the efficiency of PNA-based targeting of miR-335-5p should be verified as a therapeutic strategy in CF caused by stop-codon mutation of the CFTR gene, this approach might give appreciable results in CF cells carrying other mutations impairing the processing or stability of CFTR protein, supporting its application in personalized therapy for precision medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
37. GM1 as Adjuvant of Innovative Therapies for Cystic Fibrosis Disease.
- Author
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Mancini, Giulia, Loberto, Nicoletta, Olioso, Debora, Dechecchi, Maria Cristina, Cabrini, Giulio, Mauri, Laura, Bassi, Rosaria, Schiumarini, Domitilla, Chiricozzi, Elena, Lippi, Giuseppe, Pesce, Emanuela, Sonnino, Sandro, Pedemonte, Nicoletta, Tamanini, Anna, and Aureli, Massimo
- Subjects
CYSTIC fibrosis transmembrane conductance regulator ,CYSTIC fibrosis ,MEMBRANE proteins ,CARRIER proteins ,BURKHOLDERIA infections ,CELL membranes - Abstract
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is expressed at the apical plasma membrane (PM) of different epithelial cells. The most common mutation responsible for the onset of cystic fibrosis (CF), F508del, inhibits the biosynthesis and transport of the protein at PM, and also presents gating and stability defects of the membrane anion channel upon its rescue by the use of correctors and potentiators. This prompted a multiple drug strategy for F508delCFTR aimed simultaneously at its rescue, functional potentiation and PM stabilization. Since ganglioside GM1 is involved in the functional stabilization of transmembrane proteins, we investigated its role as an adjuvant to increase the effectiveness of CFTR modulators. According to our results, we found that GM1 resides in the same PM microenvironment as CFTR. In CF cells, the expression of the mutated channel is accompanied by a decrease in the PM GM1 content. Interestingly, by the exogenous administration of GM1, it becomes a component of the PM, reducing the destabilizing effect of the potentiator VX-770 on rescued CFTR protein expression/function and improving its stabilization. This evidence could represent a starting point for developing innovative therapeutic strategies based on the co-administration of GM1, correctors and potentiators, with the aim of improving F508del CFTR function. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
38. Synthesis and Therapeutic Applications of Iminosugars in Cystic Fibrosis.
- Author
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Esposito, Anna, D'Alonzo, Daniele, De Fenza, Maria, De Gregorio, Eliana, Tamanini, Anna, Lippi, Giuseppe, Dechecchi, Maria Cristina, and Guaragna, Annalisa
- Subjects
CYSTIC fibrosis ,IMINOSUGARS ,CYSTIC fibrosis transmembrane conductance regulator - Abstract
Iminosugars are sugar analogues endowed with a high pharmacological potential. The wide range of biological activities exhibited by these glycomimetics associated with their excellent drug profile make them attractive therapeutic candidates for several medical interventions. The ability of iminosugars to act as inhibitors or enhancers of carbohydrate-processing enzymes suggests their potential use as therapeutics for the treatment of cystic fibrosis (CF). Herein we review the most relevant advances in the field, paying attention to both the chemical synthesis of the iminosugars and their biological evaluations, resulting from in vitro and in vivo assays. Starting from the example of the marketed drug NBDNJ (N-butyl deoxynojirimycin), a variety of iminosugars have exhibited the capacity to rescue the trafficking of F508del-CFTR (deletion of F508 residue in the CF transmembrane conductance regulator), either alone or in combination with other correctors. Interesting results have also been obtained when iminosugars were considered as anti-inflammatory agents in CF lung disease. The data herein reported demonstrate that iminosugars hold considerable potential to be applied for both therapeutic purposes. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
39. Modulation of expression of IL-8 gene in bronchial epithelial cells by 5-methoxypsoralen
- Author
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Nicolis, Elena, Lampronti, Ilaria, Dechecchi, Maria Cristina, Borgatti, Monica, Tamanini, Anna, Bezzerri, Valentino, Bianchi, Nicoletta, Mazzon, Martina, Mancini, Irene, Giri, Maria Grazia, Rizzotti, Paolo, Gambari, Roberto, and Cabrini, Giulio
- Subjects
- *
GENETIC regulation , *INTERLEUKIN-8 , *BRONCHI , *EPITHELIAL cells , *PSORALENS , *NEUTROPHILS , *CYSTIC fibrosis , *RESPIRATORY diseases , *PSEUDOMONAS aeruginosa , *PATIENTS ,RESPIRATORY organ microbiology - Abstract
Abstract: Persistent recruitment of neutrophils in the bronchi of cystic fibrosis patients contributes to airway tissue damage, suggesting the importance of intervening on the expression of the neutrophil chemokine IL-8. Extracts from plants have been investigated to select components able to reduce IL-8 expression in bronchial epithelial cells challenged with Pseudomonas aeruginosa. Extracts and purified components have been added to cells 24h before pro-inflammatory challenge with P. aeruginosa and IL-8 transcription was quantified in the IB3-1 CF cells in vitro. P. aeruginosa-dependent IL-8 mRNA induction was increased by Argemone mexicana and Vernonia anthelmintica whereas no significant modification of transcription was observed with Aphanamixis polystachya, Lagerstroemia speciosa and Hemidesmus indicus. Finally, inhibition of IL-8 was observed with Polyalthia longifolia (IC50 =200μg/ml) and Aegle marmelos (IC50 =20μg/ml). Compounds from A. marmelos were isolated and identified by GC–MS. No significant effect was observed with butyl-p-tolyl sulphate, whereas the inhibition obtained with 6-methyl-4-chromanone concentration was accompanied by an anti-proliferative effect. On the contrary, 5-methoxypsoralen resulted in IL-8 inhibition at 10μM concentration, without effects on cell proliferation. In synthesis, 5-methoxypsoralen can be taken into consideration to investigate mechanisms of neutrophil chemotactic signalling and for its potential application in modulating the excessive CF lung inflammation. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
40. Unravelling the role of sphingolipids in cystic fibrosis lung disease.
- Author
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Aureli, Massimo, Schiumarini, Domitilla, Loberto, Nicoletta, Bassi, Rosaria, Tamanini, Anna, Mancini, Giulia, Tironi, Matteo, Munari, Silvia, Cabrini, Giulio, Dechecchi, Maria Cristina, and Sonnino, Sandro
- Subjects
- *
CYSTIC fibrosis , *LUNG diseases , *SPHINGOLIPIDS , *CAUSES of death , *GLYCOSPHINGOLIPIDS - Abstract
Cystic fibrosis (CF), one of the most common lethal hereditary diseases of white European populations, is caused by loss-of-function mutations in the CF Transmembrane conductance Regulator (CFTR) gene. One of the main causes of mortality is the onset of CF lung disease, which is characterized by chronic infection and inflammation resulting in the progressive remodelling, irreversible damage and fibrosis of the airways. An increasing number of studies indicate that sphingolipids are crucial players in pulmonary manifestations of CF, even if their direct involvement in CF lung disease is still unclear. In this review, we give an overview of the role of sphingolipids in CF pulmonary disease, focusing on the relationship between glycosphingolipids and lung inflammation, which represents the main hallmark of this disease. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
41. GBA2-Encoded β-Glucosidase Activity Is Involved in the Inflammatory Response to Pseudomonas aeruginosa.
- Author
-
Loberto, Nicoletta, Tebon, Maela, Lampronti, Ilaria, Marchetti, Nicola, Aureli, Massimo, Bassi, Rosaria, Giri, Maria Grazia, Bezzerri, Valentino, Lovato, Valentina, Cantù, Cinzia, Munari, Silvia, Cheng, Seng H., Cavazzini, Alberto, Gambari, Roberto, Sonnino, Sandro, Cabrini, Giulio, and Dechecchi, Maria Cristina
- Subjects
- *
GLUCOSIDASES , *CERAMIDASES , *PSEUDOMONAS aeruginosa , *CLINICAL medicine , *GLYCOMICS , *PEDIATRIC pulmonology - Abstract
Current anti-inflammatory strategies for the treatment of pulmonary disease in cystic fibrosis (CF) are limited; thus, there is continued interest in identifying additional molecular targets for therapeutic intervention. Given the emerging role of sphingolipids (SLs) in various respiratory disorders, including CF, drugs that selectively target the enzymes associated with SL metabolism are under development. Miglustat, a well-characterized iminosugar-based inhibitor of β-glucosidase 2 (GBA2), has shown promise in CF treatment because it reduces the inflammatory response to infection by P. aeruginosa and restores F508del-CFTR chloride channel activity. This study aimed to probe the molecular basis for the anti-inflammatory activity of miglustat by examining specifically the role of GBA2 following the infection of CF bronchial epithelial cells by P. aeruginosa. We also report the anti-inflammatory activity of another potent inhibitor of GBA2 activity, namely N-(5-adamantane-1-yl-methoxy)pentyl)-deoxynojirimycin (Genz-529648). In CF bronchial cells, inhibition of GBA2 by miglustat or Genz-529648 significantly reduced the induction of IL-8 mRNA levels and protein release following infection by P. aeruginosa. Hence, the present data demonstrate that the anti-inflammatory effects of miglustat and Genz-529648 are likely exerted through inhibition of GBA2. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
42. Oxidative stress and antioxidant therapy in cystic fibrosis
- Author
-
Galli, Francesco, Battistoni, Andrea, Gambari, Roberto, Pompella, Alfonso, Bragonzi, Alessandra, Pilolli, Francesca, Iuliano, Luigi, Piroddi, Marta, Dechecchi, Maria Cristina, and Cabrini, Giulio
- Subjects
- *
ANTIOXIDANTS , *OXIDATIVE stress , *CYSTIC fibrosis , *GENETIC disorders , *GENETIC regulation , *HOMEOSTASIS - Abstract
Abstract: Cystic fibrosis is a lethal autosomal recessive condition caused by a defect of the transmembrane conductance regulator gene that has a key role in cell homeostasis. A dysfunctional cystic fibrosis transmembrane conductance regulator impairs the efflux of cell anions such as chloride and bicarbonate, and also that of other solutes such as reduced glutathione. This defect produces an increased viscosity of secretions together with other metabolic defects of epithelia that ultimately promote the obstruction and fibrosis of organs. Recurrent pulmonary infections and respiratory dysfunction are main clinical consequences of these pathogenetic events, followed by pancreatic and liver insufficiency, diabetes, protein-energy malnutrition, etc. This complex comorbidity is associated with the extensive injury of different biomolecular targets by reactive oxygen species, which is the biochemical hallmark of oxidative stress. These biological lesions are particularly pronounced in the lung, in which the extent of oxidative markers parallels that of inflammatory markers between chronic events and acute exacerbations along the progression of the disease. Herein, an abnormal flux of reactive oxygen species is present by the sustained activation of neutrophils and other cystic fibrosis-derived defects in the homeostatic processes of pulmonary epithelia and lining fluids. A sub-optimal antioxidant protection is believed to represent a main contributor to oxidative stress and to the poor control of immuno-inflammatory pathways in these patients. Observed defects include an impaired reduced glutathione metabolism and lowered intake and absorption of fat-soluble antioxidants (vitamin E, carotenoids, coenzyme Q-10, some polyunsaturated fatty acids, etc.) and oligoelements (such as Se, Cu and Zn) that are involved in reactive oxygen species detoxification by means of enzymatic defenses. Oral supplements and aerosolized formulations of thiols have been used in the antioxidant therapy of this inherited disease with the main aim of reducing the extent of oxidative lesions and the rate of lung deterioration. Despite positive effects on laboratory end points, poor evidence was obtained on the side of clinical outcome so far. These aspects examined in this critical review of the literature clearly suggest that further and more rigorous trials are needed together with new generations of pharmacological tools to a more effective antioxidant and anti-inflammatory therapy of cystic fibrosis patients. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
43. Induction of IL-6 gene expression in a CF bronchial epithelial cell line by Pseudomonas aeruginosa is dependent on transcription factors belonging to the Sp1 superfamily
- Author
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Borgatti, Monica, Bezzerri, Valentino, Mancini, Irene, Nicolis, Elena, Dechecchi, Maria Cristina, Lampronti, Ilaria, Rizzotti, Paolo, Cabrini, Giulio, and Gambari, Roberto
- Subjects
- *
GENE expression , *CELL lines , *PSEUDOMONAS aeruginosa , *GRAM-negative bacteria - Abstract
Abstract: Cystic fibrosis (CF) is a genetic disease characterized by chronic bacterial lung infection, most commonly sustained by Pseudomonas aeruginosa. Upon infection, elevated concentrations of pro-inflammatory cytokines (i.e. IL-6 and IL1β) and chemokines (i.e. IL-8 and GROγ) are found in the bronchoalveolar fluid of CF patients. We report in this paper that: (a) IL-8, IL-6, IL-1β, ICAM-1, and GRO-γ genes are upregulated following infection of CF bronchial epithelial IB3-1 cells with P. aeruginosa; (b) Sp1 transcription factor activity is induced following infection of the cystic fibrosis IB3-1 and CuFi-1 cell lines; (c) inhibition of Sp1 activity using transcription factor decoy molecules leads to inhibition of the expression of IL-6 gene. From the theoretical point of view, our results demonstrate that Sp1 transcription factor activity is induced following infection of CF cells with P. aeruginosa, and that this effect is important in the activation of IL-6 gene transcription. From the practical point of view, our data sustain the potential use of decoy molecules targeting the transcription factor Sp1 to control a relevant molecule involved in the inflammatory process associated with the cystic fibrosis airway pathology. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
44. Corrigendum to “Oxidative stress and antioxidant therapy in cystic fibrosis” [Biochim. Biophys. Acta 1822 (2012) 690–713].
- Author
-
Galli, Francesco, Battistoni, Andrea, Gambari, Roberto, Pompella, Alfonso, Bragonzi, Alessandra, Pilolli, Francesca, Iuliano, Luigi, Piroddi, Marta, Dechecchi, Maria Cristina, and Cabrini, Giulio
- Subjects
- *
PUBLISHED errata , *PUBLISHED articles , *PUBLISHING , *PERIODICAL articles , *CYSTIC fibrosis treatment , *OXIDATIVE stress , *ANTIOXIDANTS - Published
- 2014
- Full Text
- View/download PDF
45. Assessing the Potential of N -Butyl-l-deoxynojirimycin (l-NBDNJ) in Models of Cystic Fibrosis as a Promising Antibacterial Agent.
- Author
-
Esposito A, Rossi A, Stabile M, Pinto G, De Fino I, Melessike M, Tamanini A, Cabrini G, Lippi G, Aureli M, Loberto N, Renda M, Galietta LJV, Amoresano A, Dechecchi MC, De Gregorio E, Bragonzi A, and Guaragna A
- Abstract
Over the past few years, l-iminosugars have revealed attractive pharmacological properties for managing rare diseases including Cystic Fibrosis (CF). The iminosugar N -butyl-l-deoxynojirimycin (l-NBDNJ, ent - 1 ), prepared by a carbohydrate-based route, was herein evaluated for its anti-inflammatory and anti-infective potential in models of CF lung disease infection. A significant decrease in the bacterial load in the airways was observed in the murine model of Pseudomonas aeruginosa chronic infection in the presence of l-NBDNJ, also accompanied by a modest reduction of inflammatory cells. Mechanistic insights into the observed activity revealed that l-NBDNJ interferes with the expression of proteins regulating cytoskeleton assembly and organization of the host cell, downregulates the main virulence factors of P. aeruginosa involved in the host response, and affects pathogen adhesion to human cells. These findings along with the observation of the absence of an in vitro bacteriostatic/bactericidal action of l-NBDNJ suggest the potential use of this glycomimetic as an antivirulence agent in the management of CF lung disease., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)
- Published
- 2024
- Full Text
- View/download PDF
46. PLCB3 Loss of Function Reduces Pseudomonas aeruginosa-Dependent IL-8 Release in Cystic Fibrosis.
- Author
-
Rimessi A, Bezzerri V, Salvatori F, Tamanini A, Nigro F, Dechecchi MC, Santangelo A, Prandini P, Munari S, Provezza L, Garreau de Loubresse N, Muller J, Ribeiro CMP, Lippi G, Gambari R, Pinton P, and Cabrini G
- Subjects
- Bronchi pathology, Calcium Signaling, Cell Line, Computer Simulation, Humans, Mucus metabolism, Mutation genetics, Phospholipase C beta chemistry, Phospholipase C beta genetics, Phospholipase C beta metabolism, Serine metabolism, Structure-Activity Relationship, Cystic Fibrosis metabolism, Cystic Fibrosis pathology, Interleukin-8 metabolism, Phospholipase C beta deficiency, Pseudomonas aeruginosa physiology
- Abstract
The lungs of patients with cystic fibrosis (CF) are characterized by an exaggerated inflammation driven by secretion of IL-8 from bronchial epithelial cells and worsened by Pseudomonas aeruginosa infection. To identify novel antiinflammatory molecular targets, we previously performed a genetic study of 135 genes of the immune response, which identified the c.2534C>T (p.S845L) variant of phospholipase C-β3 (PLCB3) as being significantly associated with mild progression of pulmonary disease. Silencing PLCB3 revealed that it potentiates the Toll-like receptor's inflammatory signaling cascade originating from CF bronchial epithelial cells. In the present study, we investigated the role of the PLCB3-S845L variant together with two synthetic mutants paradigmatic of impaired catalytic activity or lacking functional activation in CF bronchial epithelial cells. In experiments in which cells were exposed to P. aeruginosa, the supernatant of mucopurulent material from the airways of patients with CF or different agonists revealed that PLCB3-S845L has defects of 1) agonist-induced Ca
2+ release from endoplasmic reticulum and rise of Ca2+ concentration, 2) activation of conventional protein kinase C isoform β, and 3) induction of IL-8 release. These results, besides identifying S845L as a loss-of-function variant, strengthen the importance of targeting PLCB3 to mitigate the CF inflammatory response in bronchial epithelial cells without blunting the immune response.- Published
- 2018
- Full Text
- View/download PDF
47. Molecular basis of cystic fibrosis: from bench to bedside.
- Author
-
Dechecchi MC, Tamanini A, and Cabrini G
- Abstract
Cystic fibrosis (CF), is an autosomal recessive disease affecting different organs. The lung disease, characterized by recurrent and chronic bacterial infection and inflammation since infancy, is the main cause of morbidity and precocious mortality of these individuals. The innovative therapies directed to repair the defective CF gene should account for the presence of more than 200 disease-causing mutations of the CF transmembrane conductance regulator ( CFTR ) gene. The review will recall the different experimental approaches in discovering CFTR protein targeted molecules, such as the high throughput screening on chemical libraries to discover correctors and potentiators of CFTR protein, dual-acting compounds, read-through molecules, splicing defects repairing tools, CFTR "amplifiers"., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.
- Published
- 2018
- Full Text
- View/download PDF
48. A microRNA signature from serum exosomes of patients with glioma as complementary diagnostic biomarker.
- Author
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Santangelo A, Imbrucè P, Gardenghi B, Belli L, Agushi R, Tamanini A, Munari S, Bossi AM, Scambi I, Benati D, Mariotti R, Di Gennaro G, Sbarbati A, Eccher A, Ricciardi GK, Ciceri EM, Sala F, Pinna G, Lippi G, Cabrini G, and Dechecchi MC
- Subjects
- Adult, Aged, Biomarkers, Tumor, Brain Neoplasms surgery, Diagnosis, Differential, Female, Glioma surgery, Humans, Male, Middle Aged, Sensitivity and Specificity, Brain Neoplasms blood, Brain Neoplasms diagnosis, Exosomes metabolism, Glioma blood, Glioma diagnosis, MicroRNAs blood
- Abstract
Malignant gliomas, the most frequent primary brain tumors, are characterized by a dismal prognosis. Reliable biomarkers complementary to neuroradiology in the differential diagnosis of gliomas and monitoring for post-surgical progression are unmet needs. Altered expression of several microRNAs in tumour tissues from patients with gliomas compared to normal brain tissue have been described, thus supporting the rationale of using microRNA-based biomarkers. Although different circulating microRNAs were proposed in association with gliomas, they have not been introduced into clinical practice so far. Blood samples were collected from patients with high and low grade gliomas, both before and after surgical resection, and the expression of miR-21, miR-222 and miR-124-3p was measured in exosomes isolated from serum. The expression levels of miR-21, miR-222 and miR-124-3p in serum exosomes of patients with high grade gliomas were significantly higher than those of low grade gliomas and healthy controls and were sharply decreased in samples obtained after surgery. The analysis of miR-21, miR-222 and miR-124-3p in serum exosomes of patients affected by gliomas can provide a minimally invasive and innovative tool to help the differential diagnosis of gliomas at their onset in the brain and predict glioma grading and non glial metastases before surgery.
- Published
- 2018
- Full Text
- View/download PDF
49. A Peptide Nucleic Acid against MicroRNA miR-145-5p Enhances the Expression of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Calu-3 Cells.
- Author
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Fabbri E, Tamanini A, Jakova T, Gasparello J, Manicardi A, Corradini R, Sabbioni G, Finotti A, Borgatti M, Lampronti I, Munari S, Dechecchi MC, Cabrini G, and Gambari R
- Subjects
- 3' Untranslated Regions genetics, Apoptosis drug effects, Base Sequence, Binding Sites, Cell Line, Cell Proliferation drug effects, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Evolution, Molecular, Humans, MicroRNAs genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Up-Regulation drug effects, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Gene Expression Regulation drug effects, MicroRNAs metabolism, Peptide Nucleic Acids pharmacology
- Abstract
Peptide nucleic acids (PNAs) are very useful tools for gene regulation at different levels, but in particular in the last years their use for targeting microRNA (anti-miR PNAs) has provided impressive advancements. In this respect, microRNAs related to the repression of cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is defective in cystic fibrosis, are of great importance in the development of new type of treatments. In this paper we propose the use of an anti-miR PNA for targeting miR-145, a microRNA reported to suppress CFTR expression. Octaarginine-anti-miR PNA conjugates were delivered to Calu-3 cells, exerting sequence dependent targeting of miR-145-5p. This allowed to enhance expression of the miR-145 regulated CFTR gene, analyzed at mRNA (RT-qPCR, Reverse Transcription quantitative Polymerase Chain Reaction) and CFTR protein (Western blotting) level., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.
- Published
- 2017
- Full Text
- View/download PDF
50. Circulating microRNAs as emerging non-invasive biomarkers for gliomas.
- Author
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Santangelo A, Tamanini A, Cabrini G, and Dechecchi MC
- Abstract
No single circulating biomarker has been put to practice for malignant gliomas so far, the most lethal primary brain tumors. Many promising protein biomarkers such as the mutant EGFRvIII or glial fibrillary acidic protein (GFAP) have already been detected in the blood and cerebrospinal fluid (CSF) of patients with gliomas, but their clinical value is still pending validation. Furthermore, these and other proteins seem to lack sufficient sensitivity and specificity required for a successful biomarker in this clinical setting. The expression profiling of microRNAs (miRNAs) has already entered cancer clinics as diagnostic and prognostic biomarkers, for assessing tumor initiation, progression and response to treatment. Large-scale miRNA expression analyses reported both up-regulation and down-regulation of several miRNAs in tumour tissues from patients with gliomas compared to normal brain tissue, thus supporting the development of miRNA-based biomarkers. Using comprehensive high-throughput approaches, such as microarrays, different circulating miRNAs were proposed as potential biomarkers of gliomas. This review is aimed to summarize the clinical evidence about circulating miRNA biomarkers discovered to date. Mandatory issues to develop clinically validated biomarkers to improve time of diagnosis, predicting response to treatment and prognosis of patients with gliomas are also herein addresses., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.
- Published
- 2017
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