864 results on '"Rimessi A"'
Search Results
2. SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation
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Bezzerri, Valentino, Gentili, Valentina, Api, Martina, Finotti, Alessia, Papi, Chiara, Tamanini, Anna, Boni, Christian, Baldisseri, Elena, Olioso, Debora, Duca, Martina, Tedesco, Erika, Leo, Sara, Borgatti, Monica, Volpi, Sonia, Pinton, Paolo, Cabrini, Giulio, Gambari, Roberto, Blasi, Francesco, Lippi, Giuseppe, Rimessi, Alessandro, Rizzo, Roberta, and Cipolli, Marco
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- 2023
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3. Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit cancer growth
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Costantino, Luca, Ferrari, Stefania, Santucci, Matteo, Salo-Ahen, Outi MH, Carosati, Emanuele, Franchini, Silvia, Lauriola, Angela, Pozzi, Cecilia, Trande, Matteo, Gozzi, Gaia, Saxena, Puneet, Cannazza, Giuseppe, Losi, Lorena, Cardinale, Daniela, Venturelli, Alberto, Quotadamo, Antonio, Linciano, Pasquale, Tagliazucchi, Lorenzo, Moschella, Maria Gaetana, Guerrini, Remo, Pacifico, Salvatore, Luciani, Rosaria, Genovese, Filippo, Henrich, Stefan, Alboni, Silvia, Santarem, Nuno, da Silva Cordeiro, Anabela, Giovannetti, Elisa, Peters, Godefridus J, Pinton, Paolo, Rimessi, Alessandro, Cruciani, Gabriele, Stroud, Robert M, Wade, Rebecca C, Mangani, Stefano, Marverti, Gaetano, D'Arca, Domenico, Ponterini, Glauco, and Costi, Maria Paola
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Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biological Sciences ,Women's Health ,Biotechnology ,Orphan Drug ,Rare Diseases ,Cancer ,Digestive Diseases ,Ovarian Cancer ,5.1 Pharmaceuticals ,Female ,Animals ,Mice ,Humans ,Binding Sites ,Thymidylate Synthase ,Fluorouracil ,Ovarian Neoplasms ,Enzyme Inhibitors ,thymidylate synthase ,protein dimer destabilizers ,cancer growth inhibition ,proteasomal degradation ,enzyme dissociative inhibition mechanism ,target engagement ,Human ,biochemistry ,cancer biology ,chemical biology ,human ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces over-expression of this protein and development of drug resistance. We thus pursued an alternative strategy that led us to the discovery of TS-dimer destabilizers. These compounds bind at the monomer-monomer interface and shift the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers. A structural, spectroscopic, and kinetic investigation has provided evidence and quantitative information on the effects of the interaction of these small molecules with hTS. Focusing on the best among them, E7, we have shown that it inhibits hTS in cancer cells and accelerates its proteasomal degradation, thus causing a decrease in the enzyme intracellular level. E7 also showed a superior anticancer profile to fluorouracil in a mouse model of human pancreatic and ovarian cancer. Thus, over sixty years after the discovery of the first TS prodrug inhibitor, fluorouracil, E7 breaks the link between TS inhibition and enhanced expression in response, providing a strategy to fight drug-resistant cancers.
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- 2022
4. Calcium signaling around Mitochondria Associated Membranes (MAMs)
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Rimessi Alessandro, Poletti Federica, Missiroli Sonia, Marchi Saverio, Giorgi Carlotta, De Marchi Elena, Bonora Massimo, Bononi Angela, Agnoletto Chiara, Suski Jan M, Patergnani Simone, Duszynski Jerzy, Wieckowski Mariusz R, and Pinton Paolo
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Medicine ,Cytology ,QH573-671 - Abstract
Abstract Calcium (Ca2+) homeostasis is fundamental for cell metabolism, proliferation, differentiation, and cell death. Elevation in intracellular Ca2+ concentration is dependent either on Ca2+ influx from the extracellular space through the plasma membrane, or on Ca2+ release from intracellular Ca2+ stores, such as the endoplasmic/sarcoplasmic reticulum (ER/SR). Mitochondria are also major components of calcium signalling, capable of modulating both the amplitude and the spatio-temporal patterns of Ca2+ signals. Recent studies revealed zones of close contact between the ER and mitochondria called MAMs (Mitochondria Associated Membranes) crucial for a correct communication between the two organelles, including the selective transmission of physiological and pathological Ca2+ signals from the ER to mitochondria. In this review, we summarize the most up-to-date findings on the modulation of intracellular Ca2+ release and Ca2+ uptake mechanisms. We also explore the tight interplay between ER- and mitochondria-mediated Ca2+ signalling, covering the structural and molecular properties of the zones of close contact between these two networks.
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- 2011
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5. SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation
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Valentino Bezzerri, Valentina Gentili, Martina Api, Alessia Finotti, Chiara Papi, Anna Tamanini, Christian Boni, Elena Baldisseri, Debora Olioso, Martina Duca, Erika Tedesco, Sara Leo, Monica Borgatti, Sonia Volpi, Paolo Pinton, Giulio Cabrini, Roberto Gambari, Francesco Blasi, Giuseppe Lippi, Alessandro Rimessi, Roberta Rizzo, and Marco Cipolli
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Science - Abstract
Patients with cystic fibrosis are not reporting particularly sever outcomes upon SARS-CoV-2 infection. Here, the authors demonstrate decreased ACE2 levels is cystic fibrosis airway epithelia associated with impaired viral entry and replication.
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- 2023
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6. Control of mitochondrial functions by Pseudomonas aeruginosa in cystic fibrosis
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Pellielo, Giulia, primary, Agyapong, Esther Densu, additional, Pinton, Paolo, additional, and Rimessi, Alessandro, additional
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- 2023
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7. Management of COVID-19 related tracheal stenosis: The state of art
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Riccardo Orlandi, Federico Raveglia, Matteo Calderoni, Enrico Mario Cassina, Ugo Cioffi, Angelo Guttadauro, Lidia Libretti, Emanuele Pirondini, Arianna Rimessi, Antonio Tuoro, and Eliseo Passera
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tracheal stenosis ,thoracic surgery ,endoscopic thoracic surgery ,COVID-19 ,tracheal procedures ,Surgery ,RD1-811 - Abstract
Tracheal stenosis (TS) is a debilitating disease promoted by pathologic narrowing of the trachea. The acute respiratory distress syndrome caused by COVID-19 has been demonstrated to trigger enhanced inflammatory response and to require prolonged invasive mechanical ventilation as well as high frequency of re-intubation or emergency intubation, thus increasing the rate and complexity of TS. The standard-of-care of COVID-19-related tracheal complications has yet to be established and this is a matter of concern. This review aims at collecting latest evidence on this disease, providing an exhaustive overview on its distinctive features and open issues, and investigating different diagnostic and therapeutic strategies to handle COVID-19-induced TS, focusing on endoscopic versus open surgical approach. The former encompasses bronchoscopic procedures: electrocautery or laser-assisted incisions, ballooning dilation, submucosal steroid injection, endoluminal stenting. The latter consists of tracheal resection with end-to-end anastomosis. As a rule, traditionally, the endoscopic management is restricted to short, low-grade, and simple TS, whereas the open techniques are employed in long, high-grade, and complex TS. However, the critical conditions or extreme comorbidities of several COVID-19 patients, as well as the marked inflammation in tracheal mucosa, have led some authors to apply endoscopic management also in complex TS, recording acceptable results. Although severe COVID-19 seems to be an issue of the past, its long-term complications are still unknown and considering the increased rate and complexity of TS in these patients, we strongly believe that it is worth to focus on it, attempting to find the best management strategy for COVID-19-related TS.
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- 2023
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8. Post-intubation iatrogenic tracheobronchial injuries: The state of art
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Eliseo Passera, Riccardo Orlandi, Matteo Calderoni, Enrico Mario Cassina, Ugo Cioffi, Angelo Guttadauro, Lidia Libretti, Emanuele Pirondini, Arianna Rimessi, Antonio Tuoro, and Federico Raveglia
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iatrogenic tracheal injury ,tracheal surgery ,thoracic surgery ,endoscopy ,tracheobronchial laceration ,Surgery ,RD1-811 - Abstract
Iatrogenic tracheobronchial injury (ITI) is an infrequent but potentially life-threatening disease, with significant morbidity and mortality rates. Its incidence is presumably underestimated since several cases are underrecognized and underreported. Causes of ITI include endotracheal intubation (EI) or percutaneous tracheostomy (PT). Most frequent clinical manifestations are subcutaneous emphysema, pneumomediastinum and unilateral or bilateral pneumothorax, even if occasionally ITI can occur without significant symptoms. Diagnosis mainly relies on clinical suspicion and CT scan, although flexible bronchoscopy remains the gold standard, allowing to identify location and size of the injury. EI and PT related ITIs more commonly consist of longitudinal tear involving the pars membranacea. Based on the depth of tracheal wall injury, Cardillo and colleagues proposed a morphologic classification of ITIs, attempting to standardize their management. Nevertheless, in literature there are no unambiguous guidelines on the best therapeutic modality: management and its timing remain controversial. Historically, surgical repair was considered the gold standard, mainly in high-grade lesions (IIIa-IIIb), carrying high morbi-mortality rates, but currently the development of promising endoscopic techniques through rigid bronchoscopy and stenting could allow for bridge treatment, delaying surgical approach after improving general conditions of the patient, or even for definitive repair, ensuring lower morbi-mortality rates especially in high-risk surgical candidates. Our perspective review will cover all the above issues, aiming at providing an updated and clear diagnostic-therapeutic pathway protocol, which could be applied in case of unexpected ITI.
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- 2023
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9. Overview of CF lung pathophysiology
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Cabrini, Giulio, Rimessi, Alessandro, Borgatti, Monica, Pinton, Paolo, and Gambari, Roberto
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- 2022
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10. Calcium dysregulation in heart diseases: Targeting calcium channels to achieve a correct calcium homeostasis
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Morciano, Giampaolo, Rimessi, Alessandro, Patergnani, Simone, Vitto, Veronica A.M., Danese, Alberto, Kahsay, Asrat, Palumbo, Laura, Bonora, Massimo, Wieckowski, Mariusz R., Giorgi, Carlotta, and Pinton, Paolo
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- 2022
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11. The NLRP3 Inflammasome in Neurodegenerative Disorders: Insights from Epileptic Models
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Laura Palumbo, Marianna Carinci, Annunziata Guarino, Laila Asth, Silvia Zucchini, Sonia Missiroli, Alessandro Rimessi, Paolo Pinton, and Carlotta Giorgi
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neuroinflammation ,neurodegeneration ,NLRP3 inflammasome ,epilepsy ,epileptogenesis ,kainic acid ,Biology (General) ,QH301-705.5 - Abstract
Neuroinflammation represents a dynamic process of defense and protection against the harmful action of infectious agents or other detrimental stimuli in the central nervous system (CNS). However, the uncontrolled regulation of this physiological process is strongly associated with serious dysfunctional neuronal issues linked to the progression of CNS disorders. Moreover, it has been widely demonstrated that neuroinflammation is linked to epilepsy, one of the most prevalent and serious brain disorders worldwide. Indeed, NLRP3, one of the most well-studied inflammasomes, is involved in the generation of epileptic seizures, events that characterize this pathological condition. In this context, several pieces of evidence have shown that the NLRP3 inflammasome plays a central role in the pathophysiology of mesial temporal lobe epilepsy (mTLE). Based on an extensive review of the literature on the role of NLRP3-dependent inflammation in epilepsy, in this review we discuss our current understanding of the connection between NLRP3 inflammasome activation and progressive neurodegeneration in epilepsy. The goal of the review is to cover as many of the various known epilepsy models as possible, providing a broad overview of the current literature. Lastly, we also propose some of the present therapeutic strategies targeting NLRP3, aiming to provide potential insights for future studies.
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- 2023
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12. RNA-seq in DMD urinary stem cells recognized muscle-related transcription signatures and addressed the identification of atypical mutations by whole-genome sequencing
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Falzarano, Maria S., Grilli, Andrea, Zia, Silvia, Fang, Mingyan, Rossi, Rachele, Gualandi, Francesca, Rimessi, Paola, El Dani, Reem, Fabris, Marina, Lu, Zhiyuan, Li, Wenyan, Mongini, Tiziana, Ricci, Federica, Pegoraro, Elena, Bello, Luca, Barp, Andrea, Sansone, Valeria A., Hegde, Madhuri, Roda, Barbara, Reschiglian, Pierluigi, Bicciato, Silvio, Selvatici, Rita, and Ferlini, Alessandra
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- 2022
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13. The 'mitochondrial stress responses': the 'Dr. Jekyll and Mr. Hyde' of neuronal disorders
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Simone Patergnani, Giampaolo Morciano, Marianna Carinci, Sara Leo, Paolo Pinton, and Alessandro Rimessi
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alzheimer’s disease ,apoptosis ,mitochondrial dynamics ,mito-inflammation ,mitophagy ,multiple sclerosis ,neurodegeneration ,parkinson’s disease ,uprmt ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Neuronal disorders are associated with a profound loss of mitochondrial functions caused by various stress conditions, such as oxidative and metabolic stress, protein folding or import defects, and mitochondrial DNA alteration. Cells engage in different coordinated responses to safeguard mitochondrial homeostasis. In this review, we will explore the contribution of mitochondrial stress responses that are activated by the organelle to perceive these dangerous conditions, keep them under control and rescue the physiological condition of nervous cells. In the sections to come, particular attention will be dedicated to analyzing how compensatory mitochondrial hyperfusion, mitophagy, mitochondrial unfolding protein response, and apoptosis impact human neuronal diseases. Finally, we will discuss the relevance of the new concept: the “mito-inflammation”, a mitochondria-mediated inflammatory response that is recently found to cover a relevant role in the pathogenesis of diverse inflammatory-related diseases, including neuronal disorders.
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- 2022
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14. Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit cancer growth
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Luca Costantino, Stefania Ferrari, Matteo Santucci, Outi MH Salo-Ahen, Emanuele Carosati, Silvia Franchini, Angela Lauriola, Cecilia Pozzi, Matteo Trande, Gaia Gozzi, Puneet Saxena, Giuseppe Cannazza, Lorena Losi, Daniela Cardinale, Alberto Venturelli, Antonio Quotadamo, Pasquale Linciano, Lorenzo Tagliazucchi, Maria Gaetana Moschella, Remo Guerrini, Salvatore Pacifico, Rosaria Luciani, Filippo Genovese, Stefan Henrich, Silvia Alboni, Nuno Santarem, Anabela da Silva Cordeiro, Elisa Giovannetti, Godefridus J Peters, Paolo Pinton, Alessandro Rimessi, Gabriele Cruciani, Robert M Stroud, Rebecca C Wade, Stefano Mangani, Gaetano Marverti, Domenico D'Arca, Glauco Ponterini, and Maria Paola Costi
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thymidylate synthase ,protein dimer destabilizers ,cancer growth inhibition ,proteasomal degradation ,enzyme dissociative inhibition mechanism ,target engagement ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces over-expression of this protein and development of drug resistance. We thus pursued an alternative strategy that led us to the discovery of TS-dimer destabilizers. These compounds bind at the monomer-monomer interface and shift the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers. A structural, spectroscopic, and kinetic investigation has provided evidence and quantitative information on the effects of the interaction of these small molecules with hTS. Focusing on the best among them, E7, we have shown that it inhibits hTS in cancer cells and accelerates its proteasomal degradation, thus causing a decrease in the enzyme intracellular level. E7 also showed a superior anticancer profile to fluorouracil in a mouse model of human pancreatic and ovarian cancer. Thus, over sixty years after the discovery of the first TS prodrug inhibitor, fluorouracil, E7 breaks the link between TS inhibition and enhanced expression in response, providing a strategy to fight drug-resistant cancers.
- Published
- 2022
- Full Text
- View/download PDF
15. The Tricky Connection between Extracellular Vesicles and Mitochondria in Inflammatory-Related Diseases
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Tommaso Di Mambro, Giulia Pellielo, Esther Densu Agyapong, Marianna Carinci, Diego Chianese, Carlotta Giorgi, Giampaolo Morciano, Simone Patergnani, Paolo Pinton, and Alessandro Rimessi
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mitochondria ,extracellular vesicles ,mitochondria-derived vesicles ,mitovesicles ,inflammation ,intercellular communication ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Mitochondria are organelles present in almost all eukaryotic cells, where they represent the main site of energy production. Mitochondria are involved in several important cell processes, such as calcium homeostasis, OXPHOS, autophagy, and apoptosis. Moreover, they play a pivotal role also in inflammation through the inter-organelle and inter-cellular communications, mediated by the release of mitochondrial damage-associated molecular patterns (mtDAMPs). It is currently well-documented that in addition to traditional endocrine and paracrine communication, the cells converse via extracellular vesicles (EVs). These small membrane-bound particles are released from cells in the extracellular milieu under physio-pathological conditions. Importantly, EVs have gained much attention for their crucial role in inter-cellular communication, translating inflammatory signals into recipient cells. EVs cargo includes plasma membrane and endosomal proteins, but EVs also contain material from other cellular compartments, including mitochondria. Studies have shown that EVs may transport mitochondrial portions, proteins, and/or mtDAMPs to modulate the metabolic and inflammatory responses of recipient cells. Overall, the relationship between EVs and mitochondria in inflammation is an active area of research, although further studies are needed to fully understand the mechanisms involved and how they may be targeted for therapeutic purposes. Here, we have reported and discussed the latest studies focused on this fascinating and recent area of research, discussing of tricky connection between mitochondria and EVs in inflammatory-related diseases.
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- 2023
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16. The Role of Surgery in Patients with COVID-19-Related Thoracic Complications
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Federico Raveglia, Marco Scarci, Arianna Rimessi, Riccardo Orlandi, Paola Rebora, Ugo Cioffi, Angelo Guttadauro, Enrico Ruffini, Mauro Benvenuti, Giuseppe Cardillo, Davide Patrini, Fernando Vannucci, Nasser Yusuf, Pramoj Jindal, and Robert Cerfolio
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COVID-19 ,complications ,thoracic surgery ,mortality ,surgery ,Surgery ,RD1-811 - Abstract
ObjectivePatients with several thoracic complications induced by SARS-CoV-2 infection may benefit from surgery, but its role in this condition is largely unknown, and many surgeons’ advice against any surgical referrals. Our aim is to investigate the efficacy and safety of surgery in COVID-19 patients with thoracic complications requiring surgery.MethodsWe designed a multicenter observational study, involving nine thoracic surgery departments, evaluating patients who developed thoracic complications in hospital, surgically managed from March 1, 2020, to May 31, 2021. An overall 30-day mortality was obtained by using the Kaplan–Meier method. Multivariable Cox regression model and logistic models were applied to identify the variables associated with mortality and postoperative complications.ResultsAmong 83 patients, 33 (40%) underwent surgery for complicated pneumothorax, 17 (20.5%) for pleural empyema, 13 (15.5%) for hemothorax, 8 (9.5%) for hemoptysis, 5 patients (6%) for lung abscess, 4 (5%) for infected pneumatoceles, and 3 (3.5%) for other causes. Within 30 days of surgery, 60 patients (72%) survived. At multivariable analysis, age (HR 1.05 [95% CI, 1.01, 1.09], p = 0.022), pulmonary hypertension (HR 3.98 [95% CI, 1.09, 14.5], p = 0.036), renal failure (HR 2.91 [95% CI, 1.19, 7.10], p-value 0.019), thoracotomy (HR 4.90 [95% CI, 1.84, 13.1], p-value 0.001) and infective affections (HR 0.17 [95% CI, 0.05, 0.58], p-value 0.004) were found to be independent prognostic risk factors for 30-day mortality. Age (OR 1.05 [95% CI, 1.01, 1.10], p = 0.023) and thoracotomy (OR 3.85 [95% CI, 1.35, 12.0] p = 0.014) became significant predictors for 30-day morbidity.ConclusionSurgical management of COVID-19-related thoracic complications is affected by high mortality and morbidity rates, but a 72% survival rate still seems to be satisfactory with a rescue intent. Younger patients without pulmonary hypertension, without renal insufficiency and undergoing surgery for infectious complications appear to have a better prognosis.
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- 2022
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17. Testing seed germination from herbaria: Application of seed quality enhancement techniques and implication for plant resurrection and conservation.
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Albani Rocchetti, Giulia, Brancaleoni, Lisa, Caneva, Giulia, Cona, Alessandra, Fabrini, Giuseppe, Fraudentali, Ilaria, Galasso, Gabriele, Godefroid, Sandrine, Iberite, Mauro, Lastrucci, Lorenzo, Loze, Laurence, Mayer, Alfred, Mondoni, Andrea, Orsenigo, Simone, Porro, Francesco, Stauffer, Fred, Rimessi, Alice, Tilia, Agnese, Volpi, Annarita, and Abeli, Thomas
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BOTANICAL specimens ,GERMINATION ,PLANT conservation ,BIOLOGICAL extinction ,HERBARIA ,SEED quality ,NATURAL history - Abstract
Herbaria are an important source of data and material useful in many fields, including plant conservation. Seeds preserved in herbarium specimens may have the potential to germinate, although few studies focused on this topic. Here, the first systematic assessment of six techniques, including priming techniques and melatonin application, aimed at improving the germination of seeds from herbarium specimens is presented. Seed germination of 26 species common in Europe, some of which congeneric to extinct species, collected in herbaria and in the wild (20,549 seeds in total, including 19,509 from 297 herbarium specimens from 8 different herbaria) was tested with the following treatments: exogenous melatonin addition to the germination medium, priming with melatonin, osmopriming, hydropriming for 24 and 48 hours, standard soil, heat sterilization and gibberellins addition. More than 85% of the fresh seeds and 1% of the seeds collected in herbaria germinated, including seeds older than 50 years. Data show that treatment with exogenous melatonin had a positive effect on the germination of fresh seeds, but a negative effect on the germination of herbarium‐derived seeds. Furthermore, osmopriming treatment had a slightly positive effect on the germination of herbarium‐derived seeds. Osmopriming and exogenous melatonin addition seem to be promising techniques that need further investigation and improvement and might be useful for the development of an optimal germination protocol for old and herbarium‐derived seeds. The germination of seeds from herbaria could be an important tool in plant conservation, with the aim of reversing the extinction trend of many species through de‐extinction, safeguarding biodiversity, and genetic variability. This study provides preliminary data for the development of germination protocols, especially for old seeds of species of conservation interest, to maximise the chance of recovering lost genetic diversity and leading to the first de‐extinction ever. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus
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M. Grandis, L. Obici, M. Luigetti, C. Briani, F. Benedicenti, G. Bisogni, M. Canepa, F. Cappelli, C. Danesino, G. M. Fabrizi, S. Fenu, G. Ferrandes, C. Gemelli, F. Manganelli, A. Mazzeo, L. Melchiorri, F. Perfetto, L. G. Pradotto, P. Rimessi, G. Tini, S. Tozza, L. Trevisan, D. Pareyson, and P. Mandich
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Attrv ,Hereditary transthyretin amyloidosis ,Pre-symptomatic genetic testing ,PST ,Medicine - Abstract
Abstract Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington’s disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients’ characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.
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- 2020
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19. Calcium dysregulation in heart diseases: Targeting calcium channels to achieve a correct calcium homeostasis
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Giampaolo Morciano, Alessandro Rimessi, Simone Patergnani, Veronica A.M. Vitto, Alberto Danese, Asrat Kahsay, Laura Palumbo, Massimo Bonora, Mariusz R. Wieckowski, Carlotta Giorgi, and Paolo Pinton
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Calcium channels ,Mitochondria ,Sarcoplasmic reticulum ,Heart disease ,Therapy ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Intracellular calcium signaling is a universal language source shared by the most part of biological entities inside cells that, all together, give rise to physiological and functional anatomical units, the organ. Although preferentially recognized as signaling between cell life and death processes, in the heart it assumes additional relevance considered the importance of calcium cycling coupled to ATP consumption in excitation-contraction coupling. The concerted action of a plethora of exchangers, channels and pumps inward and outward calcium fluxes where needed, to convert energy and electric impulses in muscle contraction. All this without realizing it, thousands of times, every day. An improper function of those proteins (i.e., variation in expression, mutations onset, dysregulated channeling, differential protein-protein interactions) being part of this signaling network triggers a short circuit with severe acute and chronic pathological consequences reported as arrhythmias, cardiac remodeling, heart failure, reperfusion injury and cardiomyopathies. By acting with chemical, peptide-based and pharmacological modulators of these players, a correction of calcium homeostasis can be achieved accompanied by an amelioration of clinical symptoms.This review will focus on all those defects in calcium homeostasis which occur in the most common cardiac diseases, including myocardial infarction, arrhythmia, hypertrophy, heart failure and cardiomyopathies. This part will be introduced by the state of the art on the proteins involved in calcium homeostasis in cardiomyocytes and followed by the therapeutic treatments that to date, are able to target them and to revert the pathological phenotype.
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- 2022
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20. PLCγ1 suppression promotes the adaptation of KRAS-mutant lung adenocarcinomas to hypoxia
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Saliakoura, Maria, Rossi Sebastiano, Matteo, Pozzato, Chiara, Heidel, Florian H., Schnöder, Tina M., Savic Prince, Spasenija, Bubendorf, Lukas, Pinton, Paolo, A. Schmid, Ralph, Baumgartner, Johanna, Freigang, Stefan, Berezowska, Sabina A., Rimessi, Alessandro, and Konstantinidou, Georgia
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- 2020
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21. RNA-seq in DMD urinary stem cells recognized muscle-related transcription signatures and addressed the identification of atypical mutations by whole-genome sequencing
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Maria S. Falzarano, Andrea Grilli, Silvia Zia, Mingyan Fang, Rachele Rossi, Francesca Gualandi, Paola Rimessi, Reem El Dani, Marina Fabris, Zhiyuan Lu, Wenyan Li, Tiziana Mongini, Federica Ricci, Elena Pegoraro, Luca Bello, Andrea Barp, Valeria A. Sansone, Madhuri Hegde, Barbara Roda, Pierluigi Reschiglian, Silvio Bicciato, Rita Selvatici, and Alessandra Ferlini
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Genetics ,QH426-470 - Abstract
Summary: Urinary stem cells (USCs) are a non-invasive, simple, and affordable cell source to study human diseases. Here we show that USCs are a versatile tool for studying Duchenne muscular dystrophy (DMD), since they are able to address RNA signatures and atypical mutation identification. Gene expression profiling of DMD individuals’ USCs revealed a profound deregulation of inflammation, muscle development, and metabolic pathways that mirrors the known transcriptional landscape of DMD muscle and worsens following USCs’ myogenic transformation. This pathogenic transcription signature was reverted by an exon-skipping corrective approach, suggesting the utility of USCs in monitoring DMD antisense therapy. The full DMD transcript profile performed in USCs from three undiagnosed DMD individuals addressed three splicing abnormalities, which were decrypted and confirmed as pathogenic variations by whole-genome sequencing (WGS). This combined genomic approach allowed the identification of three atypical and complex DMD mutations due to a deep intronic variation and two large inversions, respectively. All three mutations affect DMD gene splicing and cause a lack of dystrophin protein production, and one of these also generates unique fusion genes and transcripts. Further characterization of USCs using a novel cell-sorting technology (Celector) highlighted cell-type variability and the representation of cell-specific DMD isoforms. Our comprehensive approach to USCs unraveled RNA, DNA, and cell-specific features and demonstrated that USCs are a robust tool for studying and diagnosing DMD.
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- 2022
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22. Post-intubation iatrogenic tracheobronchial injuries: The state of art
- Author
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Passera, E, Orlandi, R, Calderoni, M, Cassina, E, Cioffi, U, Guttadauro, A, Libretti, L, Pirondini, E, Rimessi, A, Tuoro, A, Raveglia, F, Passera E., Orlandi R., Calderoni M., Cassina E. M., Cioffi U., Guttadauro A., Libretti L., Pirondini E., Rimessi A., Tuoro A., Raveglia F., Passera, E, Orlandi, R, Calderoni, M, Cassina, E, Cioffi, U, Guttadauro, A, Libretti, L, Pirondini, E, Rimessi, A, Tuoro, A, Raveglia, F, Passera E., Orlandi R., Calderoni M., Cassina E. M., Cioffi U., Guttadauro A., Libretti L., Pirondini E., Rimessi A., Tuoro A., and Raveglia F.
- Abstract
Iatrogenic tracheobronchial injury (ITI) is an infrequent but potentially life-threatening disease, with significant morbidity and mortality rates. Its incidence is presumably underestimated since several cases are underrecognized and underreported. Causes of ITI include endotracheal intubation (EI) or percutaneous tracheostomy (PT). Most frequent clinical manifestations are subcutaneous emphysema, pneumomediastinum and unilateral or bilateral pneumothorax, even if occasionally ITI can occur without significant symptoms. Diagnosis mainly relies on clinical suspicion and CT scan, although flexible bronchoscopy remains the gold standard, allowing to identify location and size of the injury. EI and PT related ITIs more commonly consist of longitudinal tear involving the pars membranacea. Based on the depth of tracheal wall injury, Cardillo and colleagues proposed a morphologic classification of ITIs, attempting to standardize their management. Nevertheless, in literature there are no unambiguous guidelines on the best therapeutic modality: management and its timing remain controversial. Historically, surgical repair was considered the gold standard, mainly in high-grade lesions (IIIa-IIIb), carrying high morbi-mortality rates, but currently the development of promising endoscopic techniques through rigid bronchoscopy and stenting could allow for bridge treatment, delaying surgical approach after improving general conditions of the patient, or even for definitive repair, ensuring lower morbi-mortality rates especially in high-risk surgical candidates. Our perspective review will cover all the above issues, aiming at providing an updated and clear diagnostic-therapeutic pathway protocol, which could be applied in case of unexpected ITI.
- Published
- 2023
23. Management of COVID-19 related tracheal stenosis: The state of art
- Author
-
Orlandi, R, Raveglia, F, Calderoni, M, Cassina, E, Cioffi, U, Guttadauro, A, Libretti, L, Pirondini, E, Rimessi, A, Tuoro, A, Passera, E, Orlandi R., Raveglia F., Calderoni M., Cassina E. M., Cioffi U., Guttadauro A., Libretti L., Pirondini E., Rimessi A., Tuoro A., Passera E., Orlandi, R, Raveglia, F, Calderoni, M, Cassina, E, Cioffi, U, Guttadauro, A, Libretti, L, Pirondini, E, Rimessi, A, Tuoro, A, Passera, E, Orlandi R., Raveglia F., Calderoni M., Cassina E. M., Cioffi U., Guttadauro A., Libretti L., Pirondini E., Rimessi A., Tuoro A., and Passera E.
- Abstract
Tracheal stenosis (TS) is a debilitating disease promoted by pathologic narrowing of the trachea. The acute respiratory distress syndrome caused by COVID-19 has been demonstrated to trigger enhanced inflammatory response and to require prolonged invasive mechanical ventilation as well as high frequency of re-intubation or emergency intubation, thus increasing the rate and complexity of TS. The standard-of-care of COVID-19-related tracheal complications has yet to be established and this is a matter of concern. This review aims at collecting latest evidence on this disease, providing an exhaustive overview on its distinctive features and open issues, and investigating different diagnostic and therapeutic strategies to handle COVID-19-induced TS, focusing on endoscopic versus open surgical approach. The former encompasses bronchoscopic procedures: electrocautery or laser-assisted incisions, ballooning dilation, submucosal steroid injection, endoluminal stenting. The latter consists of tracheal resection with end-to-end anastomosis. As a rule, traditionally, the endoscopic management is restricted to short, low-grade, and simple TS, whereas the open techniques are employed in long, high-grade, and complex TS. However, the critical conditions or extreme comorbidities of several COVID-19 patients, as well as the marked inflammation in tracheal mucosa, have led some authors to apply endoscopic management also in complex TS, recording acceptable results. Although severe COVID-19 seems to be an issue of the past, its long-term complications are still unknown and considering the increased rate and complexity of TS in these patients, we strongly believe that it is worth to focus on it, attempting to find the best management strategy for COVID-19-related TS.
- Published
- 2023
24. Metformin prevents liver tumourigenesis by attenuating fibrosis in a transgenic mouse model of hepatocellular carcinoma
- Author
-
Shankaraiah, Ram C., Callegari, Elisa, Guerriero, Paola, Rimessi, Alessandro, Pinton, Paolo, Gramantieri, Laura, Silini, Enrico M., Sabbioni, Silvia, and Negrini, Massimo
- Published
- 2019
- Full Text
- View/download PDF
25. Methods to Monitor Mitophagy and Mitochondrial Quality: Implications in Cancer, Neurodegeneration, and Cardiovascular Diseases
- Author
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Patergnani, Simone, primary, Bonora, Massimo, additional, Bouhamida, Esmaa, additional, Danese, Alberto, additional, Marchi, Saverio, additional, Morciano, Giampaolo, additional, Previati, Maurizio, additional, Pedriali, Gaia, additional, Rimessi, Alessandro, additional, Anania, Gabriele, additional, Giorgi, Carlotta, additional, and Pinton, Paolo, additional
- Published
- 2021
- Full Text
- View/download PDF
26. The Multifaceted Roles of Autophagy in Infectious, Obstructive, and Malignant Airway Diseases
- Author
-
Marianna Carinci, Laura Palumbo, Giulia Pellielo, Esther Densu Agyapong, Giampaolo Morciano, Simone Patergnani, Carlotta Giorgi, Paolo Pinton, and Alessandro Rimessi
- Subjects
lung disease ,lung infectious ,autophagy ,xenophagy SARS-CoV-2 ,Respiratory Syncytial Virus ,Mycobacterium tuberculosis ,Biology (General) ,QH301-705.5 - Abstract
Autophagy is a highly conserved dynamic process by which cells deliver their contents to lysosomes for degradation, thus ensuring cell homeostasis. In response to environmental stress, the induction of autophagy is crucial for cell survival. The dysregulation of this degradative process has been implicated in a wide range of pathologies, including lung diseases, representing a relevant potential target with significant clinical outcomes. During lung disease progression and infections, autophagy may exert both protective and harmful effects on cells. In this review, we will explore the implications of autophagy and its selective forms in several lung infections, such as SARS-CoV-2, Respiratory Syncytial Virus (RSV) and Mycobacterium tuberculosis (Mtb) infections, and different lung diseases such as Cystic Fibrosis (CF), Chronic Obstructive Pulmonary Disease (COPD), and Malignant Mesothelioma (MM).
- Published
- 2022
- Full Text
- View/download PDF
27. Autosomal recessive Bethlem myopathy: A clinical, genetic and functional study
- Author
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Caria, Filomena, Cescon, Matilde, Gualandi, Francesca, Pichiecchio, Anna, Rossi, Rachele, Rimessi, Paola, Piccinelli, Stefano Cotti, Cassarino, Serena Gallo, Gregorio, Ilaria, Galvagni, Anna, Ferlini, Alessandra, Padovani, Alessandro, Bonaldo, Paolo, and Filosto, Massimiliano
- Published
- 2019
- Full Text
- View/download PDF
28. Standardization of Procedures to Contain Cost and Reduce Variability of Care After the Pandemic
- Author
-
Federico Raveglia, Riccardo Orlandi, Arianna Rimessi, Fabrizio Minervini, Ugo Cioffi, Matilde De Simone, Angelo Guttadauro, and Marco Scarci
- Subjects
thoracic surgery ,lean ,pandemic (COVID-19) ,lobectomy (lung) ,sigma six ,lean six sigma ,Surgery ,RD1-811 - Abstract
The coronavirus disease 2019 (COVID-19) pandemic has changed many aspects of our private and professional routine. In particular, the lockdowns have severely affected the entire healthcare system and hospital activities, forcing it to rethink the protocols in force. We suggest that this scenario, in spite of the new challenges involving so far complex healthcare providers, may lead to the unique opportunity to rethink pathways and management of patients. Indeed, having to resume institutional activity after a long interruption that has completely canceled the previously existing schemes, healthcare providers have the unique opportunity to overcome obsolete and “we have always done in this way” model on the wave of the general desire to resume a normal life. Furthermore, the pandemic has highlighted some flaws in our health system, highlighting those critical issues that most need to be addressed. This article is a review of pre-pandemic literature addressing the use of Lean Six Sigma (LSS) and standardization processes in thoracic surgery to improve efficiency. Our goal is to identify the main issues that could be successfully improved along the entire pathway of a patient from the first referral to diagnosis, hospitalization, and surgical operation up to convalescence. Furthermore, we aim to identify the standardization processes that have been implemented to achieve significant improvements in patient outcomes while reducing costs. The methods and goals that could be used in the near future to modernize our healthcare systems are drawn up from a careful reading and interpretation in light of the pandemic of the most significant review articles in the literature.
- Published
- 2021
- Full Text
- View/download PDF
29. The NLRP3 Inflammasome in Neurodegenerative Disorders: Insights from Epileptic Models
- Author
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Palumbo, Laura, primary, Carinci, Marianna, additional, Guarino, Annunziata, additional, Asth, Laila, additional, Zucchini, Silvia, additional, Missiroli, Sonia, additional, Rimessi, Alessandro, additional, Pinton, Paolo, additional, and Giorgi, Carlotta, additional
- Published
- 2023
- Full Text
- View/download PDF
30. Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy
- Author
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Veronica Angela Maria Vitto, Silvia Bianchin, Alicia Ann Zolondick, Giulia Pellielo, Alessandro Rimessi, Diego Chianese, Haining Yang, Michele Carbone, Paolo Pinton, Carlotta Giorgi, and Simone Patergnani
- Subjects
autophagy ,cancer ,tumor suppression ,tumor promotion ,anoikis ,therapy ,Biology (General) ,QH301-705.5 - Abstract
Autophagy is an evolutionarily conserved and tightly regulated process that plays an important role in maintaining cellular homeostasis. It involves regulation of various genes that function to degrade unnecessary or dysfunctional cellular components, and to recycle metabolic substrates. Autophagy is modulated by many factors, such as nutritional status, energy level, hypoxic conditions, endoplasmic reticulum stress, hormonal stimulation and drugs, and these factors can regulate autophagy both upstream and downstream of the pathway. In cancer, autophagy acts as a double-edged sword depending on the tissue type and stage of tumorigenesis. On the one hand, autophagy promotes tumor progression in advanced stages by stimulating tumor growth. On the other hand, autophagy inhibits tumor development in the early stages by enhancing its tumor suppressor activity. Moreover, autophagy drives resistance to anticancer therapy, even though in some tumor types, its activation induces lethal effects on cancer cells. In this review, we summarize the biological mechanisms of autophagy and its dual role in cancer. In addition, we report the current understanding of autophagy in some cancer types with markedly high incidence and/or lethality, and the existing therapeutic strategies targeting autophagy for the treatment of cancer.
- Published
- 2022
- Full Text
- View/download PDF
31. Update on Calcium Signaling in Cystic Fibrosis Lung Disease
- Author
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Alessandro Rimessi, Veronica A. M. Vitto, Simone Patergnani, and Paolo Pinton
- Subjects
inflammatory disease ,calcium signaling ,lung disease ,inflammation ,cystic fibrosis ,calcium ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Cystic fibrosis (CF) is an autosomal recessive disorder characterized by mutations in the cystic fibrosis transmembrane conductance regulator gene, which causes multifunctional defects that preferentially affect the airways. Abnormal viscosity of mucus secretions, persistent pathogen infections, hyperinflammation, and lung tissue damage compose the classical pathological manifestation referred to as CF lung disease. Among the multifunctional defects associated with defective CFTR, increasing evidence supports the relevant role of perturbed calcium (Ca2+) signaling in the pathophysiology of CF lung disease. The Ca2+ ion is a critical player in cell functioning and survival. Its intracellular homeostasis is maintained by a fine balance between channels, transporters, and exchangers, mediating the influx and efflux of the ion across the plasma membrane and the intracellular organelles. An abnormal Ca2+ profile has been observed in CF cells, including airway epithelial and immune cells, with heavy repercussions on cell function, viability, and susceptibility to pathogens, contributing to proinflammatory overstimulation, organelle dysfunction, oxidative stress, and excessive cytokines release in CF lung. This review discusses the role of Ca2+ signaling in CF and how its dysregulation in airway epithelial and immune cells contributes to hyperinflammation in the CF lung. Finally, we provide an outlook on the therapeutic options that target the Ca2+ signaling to treat the CF lung disease.
- Published
- 2021
- Full Text
- View/download PDF
32. Endoplasmic Reticulum-Mitochondria Communication Through Ca2+ Signaling: The Importance of Mitochondria-Associated Membranes (MAMs)
- Author
-
Marchi, Saverio, Bittremieux, Mart, Missiroli, Sonia, Morganti, Claudia, Patergnani, Simone, Sbano, Luigi, Rimessi, Alessandro, Kerkhofs, Martijn, Parys, Jan B., Bultynck, Geert, Giorgi, Carlotta, Pinton, Paolo, COHEN, IRUN R., Series editor, LAJTHA, ABEL, Series editor, LAMBRIS, JOHN D., Series editor, PAOLETTI, RODOLFO, Series editor, Tagaya, Mitsuo, editor, and Simmen, Thomas, editor
- Published
- 2017
- Full Text
- View/download PDF
33. Antisense Oligonucleotides Conjugated with Lipophilic Compounds: Synthesis and In Vitro Evaluation of Exon Skipping in Duchenne Muscular Dystrophy
- Author
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Elena Marchesi, Rita Cortesi, Lorenzo Preti, Paola Rimessi, Maddalena Sguizzato, Matteo Bovolenta, and Daniela Perrone
- Subjects
antisense oligonucleotide ,exon skipping ,conjugation ,2′-O-methyl-phosphorothioate (2′-OMe PS) ,bile acid ,ursodeoxycholic acid (UDCA) ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Our groups previously reported that conjugation at 3′-end with ursodeoxycholic acid (UDCA) significantly enhanced in vitro exon skipping properties of ASO 51 oligonucleotide targeting the human DMD exon 51. In this study, we designed a series of lipophilic conjugates of ASO 51, to explore the influence of the lipophilic moiety on exon skipping efficiency. To this end, three bile acids and two fatty acids have been derivatized and/or modified and conjugated to ASO 51 by automatized solid phase synthesis. We measured the melting temperature (Tm) of lipophilic conjugates to evaluate their ability to form a stable duplex with the target RNA. The exon skipping efficiency has been evaluated in myogenic cell lines first in presence of a transfection agent, then in gymnotic conditions on a selection of conjugated ASO 51. In the case of 5′-UDC-ASO 51, we also evaluated the influence of PS content on exon skipping efficiency; we found that it performed better exon skipping with full PS linkages. The more efficient compounds in terms of exon skipping were found to be 5′-UDC- and 5′,3′-bis-UDC-ASO 51.
- Published
- 2022
- Full Text
- View/download PDF
34. Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus
- Author
-
Grandis, M., Obici, L., Luigetti, M., Briani, C., Benedicenti, F., Bisogni, G., Canepa, M., Cappelli, F., Danesino, C., Fabrizi, G. M., Fenu, S., Ferrandes, G., Gemelli, C., Manganelli, F., Mazzeo, A., Melchiorri, L., Perfetto, F., Pradotto, L. G., Rimessi, P., Tini, G., Tozza, S., Trevisan, L., Pareyson, D., and Mandich, P.
- Published
- 2020
- Full Text
- View/download PDF
35. Role of Cystic Fibrosis Bronchial Epithelium in Neutrophil Chemotaxis
- Author
-
Giulio Cabrini, Alessandro Rimessi, Monica Borgatti, Ilaria Lampronti, Alessia Finotti, Paolo Pinton, and Roberto Gambari
- Subjects
cystic fibrosis ,epithelium ,lung ,chemotaxis ,neutrophil ,inflammation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
A hallmark of cystic fibrosis (CF) chronic respiratory disease is an extensive neutrophil infiltrate in the mucosa filling the bronchial lumen, starting early in life for CF infants. The genetic defect of the CF Transmembrane conductance Regulator (CFTR) ion channel promotes dehydration of the airway surface liquid, alters mucus properties, and decreases mucociliary clearance, favoring the onset of recurrent and, ultimately, chronic bacterial infection. Neutrophil infiltrates are unable to clear bacterial infection and, as an adverse effect, contribute to mucosal tissue damage by releasing proteases and reactive oxygen species. Moreover, the rapid cellular turnover of lumenal neutrophils releases nucleic acids that further alter the mucus viscosity. A prominent role in the recruitment of neutrophil in bronchial mucosa is played by CF bronchial epithelial cells carrying the defective CFTR protein and are exposed to whole bacteria and bacterial products, making pharmacological approaches to regulate the exaggerated neutrophil chemotaxis in CF a relevant therapeutic target. Here we revise: (a) the major receptors, kinases, and transcription factors leading to the expression, and release of neutrophil chemokines in bronchial epithelial cells; (b) the role of intracellular calcium homeostasis and, in particular, the calcium crosstalk between endoplasmic reticulum and mitochondria; (c) the epigenetic regulation of the key chemokines; (d) the role of mutant CFTR protein as a co-regulator of chemokines together with the host-pathogen interactions; and (e) different pharmacological strategies to regulate the expression of chemokines in CF bronchial epithelial cells through novel drug discovery and drug repurposing.
- Published
- 2020
- Full Text
- View/download PDF
36. The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study
- Author
-
Marcella Neri, Rachele Rossi, Cecilia Trabanelli, Antonio Mauro, Rita Selvatici, Maria Sofia Falzarano, Noemi Spedicato, Alice Margutti, Paola Rimessi, Fernanda Fortunato, Marina Fabris, Francesca Gualandi, Giacomo Comi, Silvana Tedeschi, Manuela Seia, Chiara Fiorillo, Monica Traverso, Claudio Bruno, Emiliano Giardina, Maria Rosaria Piemontese, Giuseppe Merla, Milena Cau, Monica Marica, Carmela Scuderi, Eugenia Borgione, Alessandra Tessa, Guia Astrea, Filippo Maria Santorelli, Luciano Merlini, Marina Mora, Pia Bernasconi, Sara Gibertini, Valeria Sansone, Tiziana Mongini, Angela Berardinelli, Antonella Pini, Rocco Liguori, Massimiliano Filosto, Sonia Messina, Gianluca Vita, Antonio Toscano, Giuseppe Vita, Marika Pane, Serenella Servidei, Elena Pegoraro, Luca Bello, Lorena Travaglini, Enrico Bertini, Adele D'Amico, Manuela Ergoli, Luisa Politano, Annalaura Torella, Vincenzo Nigro, Eugenio Mercuri, and Alessandra Ferlini
- Subjects
dystrophin ,muscular dystrophy ,nationwide study ,exon skipping therapy ,read-through therapy ,Genetics ,QH426-470 - Abstract
Dystrophinopathies are inherited diseases caused by mutations in the dystrophin (DMD) gene for which testing is mandatory for genetic diagnosis, reproductive choices and eligibility for personalized trials. We genotyped the DMD gene in our Italian cohort of 1902 patients (BMD n = 740, 39%; DMD n =1162, 61%) within a nationwide study involving 11 diagnostic centers in a 10-year window (2008–2017). In DMD patients, we found deletions in 57%, duplications in 11% and small mutations in 32%. In BMD, we found deletions in 78%, duplications in 9% and small mutations in 13%. In BMD, there are a higher number of deletions, and small mutations are more frequent than duplications. Among small mutations that are generally frequent in both phenotypes, 44% of DMD and 36% of BMD are nonsense, thus, eligible for stop codon read-through therapy; 63% of all out-of-frame deletions are eligible for single exon skipping. Patients were also assigned to Italian regions and showed interesting regional differences in mutation distribution. The full genetic characterization in this large, nationwide cohort has allowed us to draw several correlations between DMD/BMD genotype landscapes and mutation frequency, mutation types, mutation locations along the gene, exon/intron architecture, and relevant protein domain, with effects on population genetic characteristics and new personalized therapies.
- Published
- 2020
- Full Text
- View/download PDF
37. Post-intubation iatrogenic tracheobronchial injuries: The state of art
- Author
-
Passera E., Orlandi R., Calderoni M., Cassina E. M., Cioffi U., Guttadauro A., Libretti L., Pirondini E., Rimessi A., Tuoro A., Raveglia F., Passera, E, Orlandi, R, Calderoni, M, Cassina, E, Cioffi, U, Guttadauro, A, Libretti, L, Pirondini, E, Rimessi, A, Tuoro, A, and Raveglia, F
- Subjects
tracheobronchial laceration ,tracheal surgery ,Surgery ,endoscopy ,iatrogenic tracheal injury ,thoracic surgery - Abstract
Iatrogenic tracheobronchial injury (ITI) is an infrequent but potentially life-threatening disease, with significant morbidity and mortality rates. Its incidence is presumably underestimated since several cases are underrecognized and underreported. Causes of ITI include endotracheal intubation (EI) or percutaneous tracheostomy (PT). Most frequent clinical manifestations are subcutaneous emphysema, pneumomediastinum and unilateral or bilateral pneumothorax, even if occasionally ITI can occur without significant symptoms. Diagnosis mainly relies on clinical suspicion and CT scan, although flexible bronchoscopy remains the gold standard, allowing to identify location and size of the injury. EI and PT related ITIs more commonly consist of longitudinal tear involving the pars membranacea. Based on the depth of tracheal wall injury, Cardillo and colleagues proposed a morphologic classification of ITIs, attempting to standardize their management. Nevertheless, in literature there are no unambiguous guidelines on the best therapeutic modality: management and its timing remain controversial. Historically, surgical repair was considered the gold standard, mainly in high-grade lesions (IIIa-IIIb), carrying high morbi-mortality rates, but currently the development of promising endoscopic techniques through rigid bronchoscopy and stenting could allow for bridge treatment, delaying surgical approach after improving general conditions of the patient, or even for definitive repair, ensuring lower morbi-mortality rates especially in high-risk surgical candidates. Our perspective review will cover all the above issues, aiming at providing an updated and clear diagnostic-therapeutic pathway protocol, which could be applied in case of unexpected ITI.
- Published
- 2023
38. Management of COVID-19 related tracheal stenosis: The state of art
- Author
-
Orlandi R., Raveglia F., Calderoni M., Cassina E. M., Cioffi U., Guttadauro A., Libretti L., Pirondini E., Rimessi A., Tuoro A., Passera E., Orlandi, R, Raveglia, F, Calderoni, M, Cassina, E, Cioffi, U, Guttadauro, A, Libretti, L, Pirondini, E, Rimessi, A, Tuoro, A, and Passera, E
- Subjects
tracheal procedure ,tracheal stenosi ,endoscopic thoracic surgery ,COVID-19 ,Surgery ,thoracic surgery - Abstract
Tracheal stenosis (TS) is a debilitating disease promoted by pathologic narrowing of the trachea. The acute respiratory distress syndrome caused by COVID-19 has been demonstrated to trigger enhanced inflammatory response and to require prolonged invasive mechanical ventilation as well as high frequency of re-intubation or emergency intubation, thus increasing the rate and complexity of TS. The standard-of-care of COVID-19-related tracheal complications has yet to be established and this is a matter of concern. This review aims at collecting latest evidence on this disease, providing an exhaustive overview on its distinctive features and open issues, and investigating different diagnostic and therapeutic strategies to handle COVID-19-induced TS, focusing on endoscopic versus open surgical approach. The former encompasses bronchoscopic procedures: electrocautery or laser-assisted incisions, ballooning dilation, submucosal steroid injection, endoluminal stenting. The latter consists of tracheal resection with end-to-end anastomosis. As a rule, traditionally, the endoscopic management is restricted to short, low-grade, and simple TS, whereas the open techniques are employed in long, high-grade, and complex TS. However, the critical conditions or extreme comorbidities of several COVID-19 patients, as well as the marked inflammation in tracheal mucosa, have led some authors to apply endoscopic management also in complex TS, recording acceptable results. Although severe COVID-19 seems to be an issue of the past, its long-term complications are still unknown and considering the increased rate and complexity of TS in these patients, we strongly believe that it is worth to focus on it, attempting to find the best management strategy for COVID-19-related TS.
- Published
- 2023
39. The Tricky Connection between Extracellular Vesicles and Mitochondria in Inflammatory-Related Diseases
- Author
-
Di Mambro, Tommaso, primary, Pellielo, Giulia, additional, Agyapong, Esther Densu, additional, Carinci, Marianna, additional, Chianese, Diego, additional, Giorgi, Carlotta, additional, Morciano, Giampaolo, additional, Patergnani, Simone, additional, Pinton, Paolo, additional, and Rimessi, Alessandro, additional
- Published
- 2023
- Full Text
- View/download PDF
40. The Role of Surgery in Patients with COVID-19-Related Thoracic Complications
- Author
-
Raveglia, F, Scarci, M, Rimessi, A, Orlandi, R, Rebora, P, Cioffi, U, Guttadauro, A, Ruffini, E, Benvenuti, M, Cardillo, G, Patrini, D, Vannucci, F, Yusuf, N, Jindal, P, Cerfolio, R, Raveglia, Federico, Scarci, Marco, Rimessi, Arianna, Orlandi, Riccardo, Rebora, Paola, Cioffi, Ugo, Guttadauro, Angelo, Ruffini, Enrico, Benvenuti, Mauro, Cardillo, Giuseppe, Patrini, Davide, Vannucci, Fernando, Yusuf, Nasser, Jindal, Pramoj, Cerfolio, Robert, Raveglia, F, Scarci, M, Rimessi, A, Orlandi, R, Rebora, P, Cioffi, U, Guttadauro, A, Ruffini, E, Benvenuti, M, Cardillo, G, Patrini, D, Vannucci, F, Yusuf, N, Jindal, P, Cerfolio, R, Raveglia, Federico, Scarci, Marco, Rimessi, Arianna, Orlandi, Riccardo, Rebora, Paola, Cioffi, Ugo, Guttadauro, Angelo, Ruffini, Enrico, Benvenuti, Mauro, Cardillo, Giuseppe, Patrini, Davide, Vannucci, Fernando, Yusuf, Nasser, Jindal, Pramoj, and Cerfolio, Robert
- Abstract
Objective: Patients with several thoracic complications induced by SARS-CoV-2 infection may benefit from surgery, but its role in this condition is largely unknown, and many surgeons’ advice against any surgical referrals. Our aim is to investigate the efficacy and safety of surgery in COVID-19 patients with thoracic complications requiring surgery. Methods: We designed a multicenter observational study, involving nine thoracic surgery departments, evaluating patients who developed thoracic complications in hospital, surgically managed from March 1, 2020, to May 31, 2021. An overall 30-day mortality was obtained by using the Kaplan–Meier method. Multivariable Cox regression model and logistic models were applied to identify the variables associated with mortality and postoperative complications. Results: Among 83 patients, 33 (40%) underwent surgery for complicated pneumothorax, 17 (20.5%) for pleural empyema, 13 (15.5%) for hemothorax, 8 (9.5%) for hemoptysis, 5 patients (6%) for lung abscess, 4 (5%) for infected pneumatoceles, and 3 (3.5%) for other causes. Within 30 days of surgery, 60 patients (72%) survived. At multivariable analysis, age (HR 1.05 [95% CI, 1.01, 1.09], p = 0.022), pulmonary hypertension (HR 3.98 [95% CI, 1.09, 14.5], p = 0.036), renal failure (HR 2.91 [95% CI, 1.19, 7.10], p-value 0.019), thoracotomy (HR 4.90 [95% CI, 1.84, 13.1], p-value 0.001) and infective affections (HR 0.17 [95% CI, 0.05, 0.58], p-value 0.004) were found to be independent prognostic risk factors for 30-day mortality. Age (OR 1.05 [95% CI, 1.01, 1.10], p = 0.023) and thoracotomy (OR 3.85 [95% CI, 1.35, 12.0] p = 0.014) became significant predictors for 30-day morbidity. Conclusion: Surgical management of COVID-19-related thoracic complications is affected by high mortality and morbidity rates, but a 72% survival rate still seems to be satisfactory with a rescue intent. Younger patients without pulmonary hypertension, without renal insufficiency and undergoing surgery for in
- Published
- 2022
41. Supplementary Methods, Figure Legends 1-6 from The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA
- Author
-
Rabellino, Andrea, primary, Carter, Brandon, primary, Konstantinidou, Georgia, primary, Wu, Shwu-Yuan, primary, Rimessi, Alessandro, primary, Byers, Lauren A., primary, Heymach, John V., primary, Girard, Luc, primary, Chiang, Cheng-Ming, primary, Teruya-Feldstein, Julie, primary, and Scaglioni, Pier Paolo, primary
- Published
- 2023
- Full Text
- View/download PDF
42. Supplementary Figure 6 from The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA
- Author
-
Rabellino, Andrea, primary, Carter, Brandon, primary, Konstantinidou, Georgia, primary, Wu, Shwu-Yuan, primary, Rimessi, Alessandro, primary, Byers, Lauren A., primary, Heymach, John V., primary, Girard, Luc, primary, Chiang, Cheng-Ming, primary, Teruya-Feldstein, Julie, primary, and Scaglioni, Pier Paolo, primary
- Published
- 2023
- Full Text
- View/download PDF
43. Supplementary Table 1 from The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA
- Author
-
Rabellino, Andrea, primary, Carter, Brandon, primary, Konstantinidou, Georgia, primary, Wu, Shwu-Yuan, primary, Rimessi, Alessandro, primary, Byers, Lauren A., primary, Heymach, John V., primary, Girard, Luc, primary, Chiang, Cheng-Ming, primary, Teruya-Feldstein, Julie, primary, and Scaglioni, Pier Paolo, primary
- Published
- 2023
- Full Text
- View/download PDF
44. Supplementary Figure 1 from The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA
- Author
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Rabellino, Andrea, primary, Carter, Brandon, primary, Konstantinidou, Georgia, primary, Wu, Shwu-Yuan, primary, Rimessi, Alessandro, primary, Byers, Lauren A., primary, Heymach, John V., primary, Girard, Luc, primary, Chiang, Cheng-Ming, primary, Teruya-Feldstein, Julie, primary, and Scaglioni, Pier Paolo, primary
- Published
- 2023
- Full Text
- View/download PDF
45. Data from The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA
- Author
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Rabellino, Andrea, primary, Carter, Brandon, primary, Konstantinidou, Georgia, primary, Wu, Shwu-Yuan, primary, Rimessi, Alessandro, primary, Byers, Lauren A., primary, Heymach, John V., primary, Girard, Luc, primary, Chiang, Cheng-Ming, primary, Teruya-Feldstein, Julie, primary, and Scaglioni, Pier Paolo, primary
- Published
- 2023
- Full Text
- View/download PDF
46. Supplementary Figure 5 from The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA
- Author
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Rabellino, Andrea, primary, Carter, Brandon, primary, Konstantinidou, Georgia, primary, Wu, Shwu-Yuan, primary, Rimessi, Alessandro, primary, Byers, Lauren A., primary, Heymach, John V., primary, Girard, Luc, primary, Chiang, Cheng-Ming, primary, Teruya-Feldstein, Julie, primary, and Scaglioni, Pier Paolo, primary
- Published
- 2023
- Full Text
- View/download PDF
47. Supplementary Figure 3 from The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA
- Author
-
Rabellino, Andrea, primary, Carter, Brandon, primary, Konstantinidou, Georgia, primary, Wu, Shwu-Yuan, primary, Rimessi, Alessandro, primary, Byers, Lauren A., primary, Heymach, John V., primary, Girard, Luc, primary, Chiang, Cheng-Ming, primary, Teruya-Feldstein, Julie, primary, and Scaglioni, Pier Paolo, primary
- Published
- 2023
- Full Text
- View/download PDF
48. Supplementary Figure 4 from The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA
- Author
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Rabellino, Andrea, primary, Carter, Brandon, primary, Konstantinidou, Georgia, primary, Wu, Shwu-Yuan, primary, Rimessi, Alessandro, primary, Byers, Lauren A., primary, Heymach, John V., primary, Girard, Luc, primary, Chiang, Cheng-Ming, primary, Teruya-Feldstein, Julie, primary, and Scaglioni, Pier Paolo, primary
- Published
- 2023
- Full Text
- View/download PDF
49. Supplementary Figure 2 from The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA
- Author
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Rabellino, Andrea, primary, Carter, Brandon, primary, Konstantinidou, Georgia, primary, Wu, Shwu-Yuan, primary, Rimessi, Alessandro, primary, Byers, Lauren A., primary, Heymach, John V., primary, Girard, Luc, primary, Chiang, Cheng-Ming, primary, Teruya-Feldstein, Julie, primary, and Scaglioni, Pier Paolo, primary
- Published
- 2023
- Full Text
- View/download PDF
50. Supplementary Figure 3 from The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA
- Author
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Pier Paolo Scaglioni, Julie Teruya-Feldstein, Cheng-Ming Chiang, Luc Girard, John V. Heymach, Lauren A. Byers, Alessandro Rimessi, Shwu-Yuan Wu, Georgia Konstantinidou, Brandon Carter, and Andrea Rabellino
- Abstract
PDF file - 126K
- Published
- 2023
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