212 results on '"Gessani A"'
Search Results
2. Insight into Elderly ALS Patients in the Emilia Romagna Region: Epidemiological and Clinical Features of Late-Onset ALS in a Prospective, Population-Based Study
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Mandrioli, Giulia Gianferrari, Ilaria Martinelli, Cecilia Simonini, Elisabetta Zucchi, Nicola Fini, Maria Caputo, Andrea Ghezzi, Annalisa Gessani, Elena Canali, Mario Casmiro, Patrizia De Massis, Marco Curro’ Dossi, Silvia De Pasqua, Rocco Liguori, Marco Longoni, Doriana Medici, Simonetta Morresi, Alberto Patuelli, Maura Pugliatti, Mario Santangelo, Elisabetta Sette, Filippo Stragliati, Emilio Terlizzi, Veria Vacchiano, Lucia Zinno, Salvatore Ferro, Amedeo Amedei, Tommaso Filippini, Marco Vinceti, ERRALS GROUP ERRALS GROUP, and Jessica
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amyotrophic lateral sclerosis ,elderly ALS ,epidemiology ,phenotype ,prognosis ,survival - Abstract
Few studies have focused on elderly (>80 years) amyotrophic lateral sclerosis (ALS) patients, who represent a fragile subgroup generally not included in clinical trials and often neglected because they are more difficult to diagnose and manage. We analyzed the clinical and genetic features of very late-onset ALS patients through a prospective, population-based study in the Emilia Romagna Region of Italy. From 2009 to 2019, 222 (13.76%) out of 1613 patients in incident cases were over 80 years old at diagnosis, with a female predominance (F:M = 1.18). Elderly ALS patients represented 12.02% of patients before 2015 and 15.91% from 2015 onwards (p = 0.024). This group presented with bulbar onset in 38.29% of cases and had worse clinical conditions at diagnosis compared to younger patients, with a lower average BMI (23.12 vs. 24.57 Kg/m2), a higher progression rate (1.43 vs. 0.95 points/month), and a shorter length of survival (a median of 20.77 vs. 36 months). For this subgroup, genetic analyses have seldom been carried out (25% vs. 39.11%) and are generally negative. Finally, elderly patients underwent less frequent nutritional- and respiratory-supporting procedures, and multidisciplinary teams were less involved at follow-up, except for specialist palliative care. The genotypic and phenotypic features of elderly ALS patients could help identify the different environmental and genetic risk factors that determine the age at which disease onset occurs. Since multidisciplinary management can improve a patient’s prognosis, it should be more extensively applied to this fragile group of patients.
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- 2023
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3. Insight into Elderly ALS Patients in the Emilia Romagna Region: Epidemiological and Clinical Features of Late-Onset ALS in a Prospective, Population-Based Study
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Gianferrari, Giulia, Martinelli, Ilaria, Simonini, Cecilia, Zucchi, Elisabetta, Fini, Nicola, Caputo, Maria, Ghezzi, Andrea, Gessani, Annalisa, Canali, Elena, Casmiro, Mario, De Massis, Patrizia, Curro' Dossi, Marco, De Pasqua, Silvia, Liguori, Rocco, Longoni, Marco, Medici, Doriana, Morresi, Simonetta, Patuelli, Alberto, Pugliatti, Maura, Santangelo, Mario, Sette, Elisabetta, Stragliati, Filippo, Terlizzi, Emilio, Vacchiano, Veria, Zinno, Lucia, Ferro, Salvatore, Amedei, Amedeo, Filippini, Tommaso, Vinceti, Marco, Errals Group, Null, and Mandrioli, Jessica
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amyotrophic lateral sclerosis ,phenotype ,elderly ALS ,epidemiology ,prognosis ,survival - Published
- 2023
4. Interplay between speech and gait variables in PD patients treated with STN-DBS: A long-term instrumental assessment
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Cavallieri, Francesco, Annalisa, Gessani, Merlo, Andrea, Campanini, Isabella, Budriesi, Carla, Fioravanti, Valentina, DI RAUSO, Giulia, Alberto, Feletti, Benedetta, Damiano, Scaltriti, Sara, Noemi, Guadagno, Bardi, Elisa, Corni, MARIA GIULIA, Antonelli, Francesca, Francesca, Cavalleri, Molinari, MARIA ANGELA, Sara, Contardi, Elisa, Menozzi, Puzzolante, Annette, Vannozzi, Giuseppe, Bergamini, Elena, Pavesi, Giacomo, Valérie, Fraix, Alessandro, Fraternali, Annibale, Versari, Lusuardi, Mirco, Biagini, Giuseppe, Serge, Pinto, Elena, Moro, and Valzania, Franco
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Parkinson’s Disease ,STN-DBS ,speech ,Gait, deep brain stimulation, levodopa, Parkinson’s Disease, speech, STN-DBS ,levodopa ,Gait ,deep brain stimulation - Published
- 2023
5. Long-term effects of subthalamic nucleus deep brain stimulation on speech in Parkinson's disease
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Gessani, Annalisa, Cavallieri, Francesco, Fioravanti, Valentina, Campanini, Isabella, Merlo, Andrea, Di Rauso, Giulia, Damiano, Benedetta, Scaltriti, Sara, Bardi, Elisa, Corni, Maria Giulia, Antonelli, Francesca, Cavalleri, Francesca, Molinari, Maria Angela, Contardi, Sara, Menozzi, Elisa, Fraternali, Alessandro, Versari, Annibale, Biagini, Giuseppe, Fraix, Valérie, Pinto, Serge, Moro, Elena, Budriesi, Carla, and Valzania, Franco
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- 2023
6. Interplay between speech and gait variables in PD patients treated with STN-DBS: a long-term instrumental assessment
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Cavallieri, Francesco, Gessani, Annalisa, Merlo, Andrea, Campanini, Isabella, Budriesi, Carla, Fioravanti, Valentina, Di Rauso, Giulia, Feletti, Alberto, Damiano, Benedetta, Scaltriti, Sara, Guagnano, Noemi, Bardi, Elisa, Corni, Maria Giulia, Antonelli, Francesca, Cavalleri, Francesca, Molinari, Maria Angela, Contardi, Sara, Menozzi, Elisa, Puzzolante, Annette, Vannozzi, Giuseppe, Bergamini, Elena, Pavesi, Giacomo, Fraix, Valérie, Meoni, Sara, Fraternali, Alessandro, Versari, Annibale, Lusuardi, Mirco, Biagini, Giuseppe, Pinto, Serge, Moro, Elena, and Valzania, Franco
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Parkinson's Disease ,STN-DBS ,speech ,levodopa ,gait ,deep brain stimulation - Published
- 2023
7. Long-term effects of bilateral subthalamic nucleus deep brain stimulation on gait disorders in Parkinson’s disease: a clinical-instrumental study
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Francesco Cavallieri, Isabella Campanini, Annalisa Gessani, Carla Budriesi, Valentina Fioravanti, Giulia Di Rauso, Alberto Feletti, Benedetta Damiano, Sara Scaltriti, Noemi Guagnano, Elisa Bardi, Maria Giulia Corni, Jessica Rossi, Francesca Antonelli, Francesca Cavalleri, Maria Angela Molinari, Sara Contardi, Elisa Menozzi, Annette Puzzolante, Giuseppe Vannozzi, Elena Bergamini, Giacomo Pavesi, Sara Meoni, Valérie Fraix, Alessandro Fraternali, Annibale Versari, Mirco Lusuardi, Giuseppe Biagini, Andrea Merlo, Elena Moro, and Franco Valzania
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Neurology ,iTUG ,Deep brain stimulation, DBS, Gait, iTUG, Parkinson’s disease, Subthalamic nucleus ,Deep brain stimulation ,Parkinson’s disease ,DBS ,Neurology (clinical) ,Gait ,Subthalamic nucleus - Published
- 2023
8. Validation of the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire for the evaluation of dysphagia in ALS patients
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Diamanti, Luca, Borrelli, Paola, Dubbioso, Raffaele, Capasso, Margherita, Morelli, Claudia, Lunetta, Christian, Petrucci, Antonio, Mora, Gabriele, Volanti, Paolo, Inghilleri, Maurizio, Tremolizzo, Lucio, Mandrioli, Jessica, Mazzini, Letizia, Vedovello, Marcella, Siciliano, Gabriele, Filosto, Massimiliano, Matà, Sabrina, Montomoli, Cristina, DYALS Study Group (Giuliana Capece, Andrea, Ghezzi, Giuseppe, Fiamingo, Francesco Pio Ausiello, Laura, Ferri, Alberto, Doretti, Eleonora, Colombo, Gianluca, Demirtzidis, Vittorio, Riso, Federica, Bianchi, Micol, Castellari, Francesca, Madonia, Ceccanti, Marco, Cambieri, Chiara, Libonati, Laura, Fanella, Gaia, Carlo, Ferrarese, Annalisa, Gessani, Carla, Budriesi, Fabiola De Marchi, Francesca, Bianchi, Cecilia, Carlesi), Diamanti, Luca, Borrelli, Paola, Dubbioso, Raffaele, Capasso, Margherita, Morelli, Claudia, Lunetta, Christian, Petrucci, Antonio, Mora, Gabriele, Volanti, Paolo, Inghilleri, Maurizio, Tremolizzo, Lucio, Mandrioli, Jessica, Mazzini, Letizia, Vedovello, Marcella, Siciliano, Gabriele, Filosto, Massimiliano, Matà, Sabrina, Montomoli, Cristina, Diamanti, L, Borrelli, P, Dubbioso, R, Capasso, M, Morelli, C, Lunetta, C, Petrucci, A, Mora, G, Volanti, P, Inghilleri, M, Tremolizzo, L, Mandrioli, J, Mazzini, L, Vedovello, M, Siciliano, G, Filosto, M, Matà, S, and Montomoli, C
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medicine.medical_specialty ,Multiple Sclerosis ,Neurology ,Dermatology ,Cronbach's alpha ,ALS ,Dysphagia ,Screening ,Humans ,Middle Aged ,Quality of Life ,Surveys and Questionnaires ,Amyotrophic Lateral Sclerosis ,Deglutition Disorders ,Internal medicine ,medicine ,Amyotrophic lateral sclerosis ,Neuroradiology ,business.industry ,Multiple sclerosis ,General Medicine ,medicine.disease ,Clinical trial ,Psychiatry and Mental health ,Neurology (clinical) ,Neurosurgery ,medicine.symptom ,business - Abstract
BACKGROUND: Dysphagia is a common symptom during the trajectory of ALS, and it can significantly impact on the quality of life and prognosis of patients. Nowadays, no specific tool for the screening of dysphagia in ALS is validated, and the approach is heterogeneous across the Italian centres. OBJECTIVE: To validate the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire, adapting the DYMUS (dysphagia in multiple sclerosis) questionnaire, for the assessment of dysphagia in ALS patients, in order to uniform the evaluations across the Italian ALS network. METHODS: We included 197 patients diagnosed with ALS following the El Escorial criteria, in sixteen Italian ALS centres between 1st December 2019 and 1st July 2020. For each patient, we collected clinical and demographic data and obtained ALSFRS-r score, ALSAQ-5 score, DYMUS score, and EAT-10 score. RESULTS: Across the 197 patients, the ratio M/F was 113/84, and the median age was 64 years (IQR 56-72.5). Bulbar patients were 20%, and spinal patients 80%. The median ALSFRSr total score of patients was 35 (IQR 28-39). DYALS score was statistically higher in bulbar ALS than in spinal ALS (median = 6, IQR 4.5-9 vs median = 1, IQR 0-5, z = 6.253, p
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- 2021
9. Highlights on the Role of Galectin-3 in Colorectal Cancer and the Preventive/Therapeutic Potential of Food-Derived Inhibitors
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Anna Aureli, Manuela Del Cornò, Beatrice Marziani, Sandra Gessani, and Lucia Conti
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Cancer Research ,Oncology - Abstract
Colorectal cancer (CRC) is a leading cause of death worldwide. Despite advances in surgical and therapeutic management, tumor metastases and resistance to therapy still represent major hurdles. CRC risk is highly modifiable by lifestyle factors, including diet, which strongly influences both cancer incidence and related mortality. Galectin-3 (Gal-3) is a multifaceted protein involved in multiple pathophysiological pathways underlying chronic inflammation and cancer. Its versatility is given by the ability to participate in a wide range of tumor-promoting processes, including cell–cell/cell–matrix interactions, cell growth regulation and apoptosis, and the immunosuppressive tumor microenvironment. This review provides an updated summary of preclinical and observational human studies investigating the pathogenetic role of Gal-3 in intestinal inflammation and CRC, as well as the potential of Gal-3 activity inhibition by plant-source food-derived bioactive compounds to control CRC onset/growth. These studies highlight both direct and immuno-mediated effects of Gal-3 on tumor growth and invasiveness and its potential role as a CRC prognostic biomarker. Substantial evidence indicates natural food-derived Gal-3 inhibitors as promising candidates for CRC prevention and therapy. However, critical issues, such as their bioavailability and efficacy, in controlled human studies need to be addressed to translate research progress into clinical applications.
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- 2022
10. Epidemiological, Clinical and Genetic Features of ALS in the Last Decade: A Prospective Population-Based Study in the Emilia Romagna Region of Italy
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Giulia, Gianferrari, Ilaria, Martinelli, Elisabetta, Zucchi, Cecilia, Simonini, Nicola, Fini, Marco, Vinceti, Salvatore, Ferro, Annalisa, Gessani, Elena, Canali, Franco, Valzania, Elisabetta, Sette, Maura, Pugliatti, Valeria, Tugnoli, Lucia, Zinno, Salvatore, Stano, Mario, Santangelo, Silvia, De Pasqua, Emilio, Terlizzi, Donata, Guidetti, Doriana, Medici, Fabrizio, Salvi, Rocco, Liguori, Veria, Vacchiano, Mario, Casmiro, Pietro, Querzani, Marco, Currò Dossi, Alberto, Patuelli, Simonetta, Morresi, Marco, Longoni, Patrizia, De Massis, Rita, Rinaldi, Annamaria, Borghi, Errals Group, Amedeo, Amedei, Jessica, Mandrioli, Gianferrari G., Martinelli I., Zucchi E., Simonini C., Fini N., Vinceti M., Ferro S., Gessani A., Canali E., Valzania F., Sette E., Pugliatti M., Tugnoli V., Zinno L., Stano S., Santangelo M., De Pasqua S., Terlizzi E., Guidetti D., Medici D., Salvi F., Liguori R., Vacchiano V., Casmiro M., Querzani P., Dossi M.C., Patuelli A., Morresi S., Longoni M., De Massis P., Rinaldi R., Borghi A., Amedei A., and Mandrioli J.
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amyotrophic lateral sclerosis ,clinical features ,epidemiology ,genetics ,incidence ,population-based registry ,Medicine (miscellaneous) ,amyotrophic lateral sclerosi ,genetic ,General Biochemistry, Genetics and Molecular Biology ,clinical feature - Abstract
Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype–phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age- and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70–75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype–genotype correlations in the ALS population of ERR.
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- 2022
11. Freezing of Gait in Parkinson's Disease Patients Treated with Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Long-Term Overview
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Giulia Di Rauso, Francesco Cavallieri, Isabella Campanini, Annalisa Gessani, Valentina Fioravanti, Alberto Feletti, Benedetta Damiano, Sara Scaltriti, Elisa Bardi, Maria Giulia Corni, Francesca Antonelli, Vittorio Rispoli, Francesca Cavalleri, Maria Angela Molinari, Sara Contardi, Elisa Menozzi, Annette Puzzolante, Jessica Rossi, Stefano Meletti, Giuseppe Biagini, Giacomo Pavesi, Valerie Fraix, Mirco Lusuardi, Alessandro Fraternali, Annibale Versari, Carla Budriesi, Elena Moro, Andrea Merlo, and Franco Valzania
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long-term ,subthalamic nucleus ,Axial symptoms ,STN-DBS ,deep brain stimulation ,freezing ,gait ,Parkinson’s disease ,Medicine (miscellaneous) ,axial symptoms ,General Biochemistry, Genetics and Molecular Biology - Abstract
Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson’s Disease (PD). However, the effects of STN-DBS on freezing of gait (FOG) are still debated, particularly in the long-term follow-up (≥5-years). The main aim of the current study is to evaluate the long-term effects of STN-DBS on FOG. Twenty STN-DBS treated PD patients were included. Each patient was assessed before surgery through a detailed neurological evaluation, including FOG score, and revaluated in the long-term (median follow-up: 5-years) in different stimulation and drug conditions. In the long term follow-up, FOG score significantly worsened in the off-stimulation/off-medication condition compared with the pre-operative off-medication assessment (z = −1.930; p = 0.05) but not in the on-stimulation/off-medication (z = −0.357; p = 0.721). There was also a significant improvement of FOG at long-term assessment by comparing on-stimulation/off-medication and off-stimulation/off-medication conditions (z = −2.944; p = 0.003). These results highlight the possible beneficial long-term effects of STN-DBS on FOG.
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- 2022
12. Added value of the instrumented Timed-Up and Go test (iTUG) in the long-term assessment of PD patients with bilateral subthalamic nucleus deep brain stimulation (STN-DBS)
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I. Campanini, F. Cavallieri, B. Damiano, S. Scaltriti, V. Fioravanti, N. Guagnano, G. Vannozzi, E. Bergamini, A. Gessani, C. Budriesi, F. Antonelli, V. Rispoli, M. Lusuardi, F. Valzania, and A. Merlo
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Rehabilitation ,Biophysics ,Orthopedics and Sports Medicine - Published
- 2022
13. Deconstructing speech alterations in episodic ataxia type 2: Perceptual-acoustic analysis in a case due to CACNA1A gene mutation
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Giacomo Argenziano, Francesco Cavallieri, Edoardo Monfrini, Annalisa Gessani, Marco Russo, Romana Rizzi, Valentina Fioravanti, Sara Grisanti, Giulia Toschi, Manuela Napoli, Rosario Pascarella, Carla Budriesi, Alessio Di Fonzo, Riccardo Zucco, and Franco Valzania
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Neurology ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2023
14. Type I Interferons as Joint Regulators of Tumor Growth and Obesity
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Sandra Gessani and Filippo Belardelli
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0301 basic medicine ,Cancer Research ,obesity ,immunoregulation ,medicine.medical_treatment ,Cellular differentiation ,Adipose tissue ,Inflammation ,Endogeny ,Review ,Biology ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,medicine ,cancer ,tumor microenvironment ,Pathological ,Chemotherapy ,Tumor microenvironment ,inflammation ,type I interferons ,Cancer ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,medicine.symptom - Abstract
Simple Summary The escalating global epidemic of overweight and obesity is a major public health and economic problem, as excess body weight represents a significant risk factor for several chronic diseases including cancer. Despite the strong scientific evidence for a link between obesity and cancer, the mechanisms involved in this interplay have not yet been fully understood. The aim of this review is to evaluate the role of type I interferons, a family of antiviral cytokines with key roles in the regulation of both obesity and cancer, highlighting how the dysregulation of the interferon system can differently affect these pathological conditions. Abstract Type I interferons (IFN-I) are antiviral cytokines endowed with multiple biological actions, including antitumor activity. Studies in mouse models and cancer patients support the concept that endogenous IFN-I play important roles in the control of tumor development and growth as well as in response to several chemotherapy/radiotherapy treatments. While IFN-I signatures in the tumor microenvironment are often considered as biomarkers for a good prognostic response to antitumor therapies, prolonged IFN-I signaling can lead to immune dysfunction, thereby promoting pathogen or tumor persistence, thus revealing the “Janus face” of these cytokines in cancer control, likely depending on timing, tissue microenvironment and cumulative levels of IFN-I signals. Likewise, IFN-I exhibit different and even opposite effects on obesity, a pathologic condition linked to cancer development and growth. As an example, evidence obtained in mouse models shows that localized expression of IFN-I in the adipose tissue results in inhibition of diet–induced obesity, while hyper-production of these cytokines by specialized cells such as plasmacytoid dendritic cells in the same tissue, can induce systemic inflammatory responses leading to obesity. Further studies in mouse models and humans should reveal the mechanisms by which IFN-I can regulate both tumor growth and obesity and to understand the role of factors such as genetic background, diet and microbioma in shaping the production and action of these cytokines under physiological and pathological conditions.
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- 2021
15. Dopaminergic Treatment Effects on Dysarthric Speech: Acoustic Analysis in a Cohort of Patients With Advanced Parkinson's Disease
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Francesco Cavallieri, Carla Budriesi, Annalisa Gessani, Sara Contardi, Valentina Fioravanti, Elisa Menozzi, Serge Pinto, Elena Moro, Franco Valzania, Francesca Antonelli, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), and Pinto, Serge
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medicine.medical_specialty ,Levodopa ,Parkinson's disease ,speech ,Audiology ,lcsh:RC346-429 ,03 medical and health sciences ,Dysarthria ,0302 clinical medicine ,dysarthria ,Rating scale ,medicine ,otorhinolaryngologic diseases ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Phonation ,levodopa ,030223 otorhinolaryngology ,lcsh:Neurology. Diseases of the nervous system ,Original Research ,business.industry ,Dopaminergic ,medicine.disease ,acoustic analysis ,Neurology ,Dyskinesia ,dyskinesias ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Cohort ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Importance: The effects of dopaminergic treatment on speech in patients with Parkinson's disease (PD) are often mixed and unclear. The aim of this study was to better elucidate those discrepancies.Methods: Full retrospective data from advanced PD patients before and after an acute levodopa challenge were collected. Acoustic analysis of spontaneous monologue and sustained phonation including several quantitative parameters [i.e., maximum phonation time (MPT); shimmer local dB] as well as the Unified Parkinson's Disease Rating Scale (UPDRS) (total scores, subscores, and items) and the Clinical Dyskinesia Rating Scale (CDRS) were performed in both the defined-OFF and -ON conditions. The primary outcome was the changes of speech parameters after levodopa intake. Secondary outcomes included the analysis of possible correlations of motor features and levodopa-induced dyskinesia (LID) with acoustic speech parameters. Statistical analysis included paired t-test between the ON and OFF data (calculated separately for male and female subgroups) and Pearson correlation between speech and motor data.Results: In 50 PD patients (male: 32; female: 18), levodopa significantly increased the MPT of sustained phonation in female patients (p < 0.01). In the OFF-state, the UPDRS part-III speech item negatively correlated with MPT (p = 0.02), whereas in the ON-state, it correlated positively with the shimmer local dB (p = 0.01), an expression of poorer voice quality. The total CDRS score and axial subscores strongly correlated with the ON-state shimmer local dB (p = 0.01 and p < 0.01, respectively).Conclusions: Our findings emphasize that levodopa has a poor effect on speech acoustic parameters. The intensity and location of LID negatively influenced speech quality.
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- 2021
16. Are we fully exploiting type I Interferons in today's fight against COVID-19 pandemic?
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Eleonora Aricò, Luciano Castiello, Laura Bracci, Sandra Gessani, and Filippo Belardelli
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0301 basic medicine ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Endocrinology, Diabetes and Metabolism ,Immunology ,Pneumonia, Viral ,Disease ,Antiviral Agents ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Betacoronavirus ,0302 clinical medicine ,Pandemic ,medicine ,Secondary Prevention ,Immunology and Allergy ,Humans ,Available drugs ,Intensive care medicine ,Pandemics ,Therapeutic strategy ,ComputingMethodologies_COMPUTERGRAPHICS ,Modalities ,business.industry ,SARS-CoV-2 ,COVID-19 ,Interferon-alpha ,Interferon-beta ,Type I Interferons COVID-19 SARS-CoV-2 Coronavirus Mucosal treatments Immunomodulation Antiviral therapy Antiviral Immune Response Beta Interferon ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunotherapy ,business ,Coronavirus Infections - Abstract
Graphical abstract, Highlights • IFN-I, in particular IFN-β, are promising drugs for SARS-CoV2 infection • Early infection in elderly patients is the best setting to exploit IFN-I immunomodulatory activity • Caution should be given in using continuous IFN-I treatments at high doses. • Mucosal IFN-I delivery is promising but deserves further clinical investigation • Attention should be paid to IFN-I treatment in patients with severe COVID-19, Coronavirus disease 2019 (COVID-19) first emerged in late 2019 in China. At the time of writing, its causative agent SARS-CoV-2 has spread worldwide infecting over 9 million individuals and causing more than 460,000 deaths. In the absence of vaccines, we are facing the dramatic challenge of controlling COVID-19 pandemic. Among currently available drugs, type I Interferons (IFN-I) – mainly IFN-α and β –represent ideal candidates given their direct and immune-mediated antiviral effects and the long record of clinical use. However, the best modalities of using these cytokines in SARS-CoV-2 infected patients is a matter of debate. Here, we discuss how we can exploit the current knowledge on IFN-I system to tailor the most promising dosing, timing and route of administration of IFN-I to the disease stage, with the final aim of making these cytokines a valuable therapeutic strategy in today's fight against COVID-19 pandemic.
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- 2020
17. A novel p.N66T mutation in exon 3 of the SOD1 gene: report of two families of ALS patients with early cognitive impairment
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Valentina Pecoraro, Tommaso Trenti, Ilaria Martinelli, Elisabetta Zucchi, Annalisa Gessani, Adriano Chiò, Nicola Fini, and Jessica Mandrioli
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Male ,ALS genetics ,animal diseases ,SOD1 ,Neuropsychological Tests ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Superoxide Dismutase-1 ,medicine ,Humans ,Cognitive Dysfunction ,Amyotrophic lateral sclerosis ,Cognitive impairment ,Gene ,cognitive impairment ,Aged ,Genetics ,business.industry ,Amyotrophic Lateral Sclerosis ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,ALS FTD ,nervous system diseases ,Pedigree ,Neurology ,Mutation (genetic algorithm) ,Mutation ,Neurology (clinical) ,ALS phenotype ,business ,familial ALS ,030217 neurology & neurosurgery - Abstract
Introduction: To date more than 180 different mutations in the SOD1 gene have been described in ALS; some of these mutations are associated to peculiar clinical features and have contributed to the...
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- 2020
18. Shaping the Innate Immune Response by Dietary Glucans: Any Role in the Control of Cancer?
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Manuela Del Cornò, Sandra Gessani, and Lucia Conti
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0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,Inflammation ,Review ,Biology ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,medicine ,cancer ,Biological response modifiers ,innate immunity ,Innate immune system ,Cancer prevention ,Cancer ,Immunotherapy ,Acquired immune system ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,nutrition ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,β-glucans ,immunotherapy ,medicine.symptom ,Function (biology) - Abstract
β-glucans represent a heterogeneous group of naturally occurring and biologically active polysaccharides found in many kinds of edible mushrooms, baker’s yeast, cereals and seaweeds, whose health-promoting effects have been known since ancient times. These compounds can be taken orally as food supplements or as part of daily diets, and are safe to use, nonimmunogenic and well tolerated. A main feature of β-glucans is their capacity to function as biological response modifiers, exerting regulatory effects on inflammation and shaping the effector functions of different innate and adaptive immunity cell populations. The potential to interfere with processes involved in the development or control of cancer makes β-glucans interesting candidates as adjuvants in antitumor therapies as well as in cancer prevention strategies. Here, the regulatory effects of dietary β-glucans on human innate immunity cells are reviewed and their potential role in cancer control is discussed.
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- 2020
19. Exploratory modeling and experimental investigation of a vibrating-stripe wind energy converter
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Gabriele Gessani, Pietro Cingi, Giulio Allesina, and Diego Angeli
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Fluid Flow and Transfer Processes ,Physics ,Wind power ,business.industry ,020209 energy ,Mechanical Engineering ,Exploratory modeling ,Modeling ,Mechanical engineering ,02 engineering and technology ,Condensed Matter Physics ,Fluttering ,Windbelt ,0202 electrical engineering, electronic engineering, information engineering ,business ,Wind energy - Published
- 2018
20. Editorial: Diet, Inflammation and Colorectal Cancer
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Sandra Gessani, Fränzel J. Van Duijnhoven, and Maria Jesus Moreno-Aliaga
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lcsh:Immunologic diseases. Allergy ,Oncology ,obesity ,medicine.medical_specialty ,Nutrition and Disease ,Colorectal cancer ,Immunology ,colorectal cancer ,Inflammation ,Dietary factors ,Voeding en Ziekte ,Internal medicine ,Humans ,Immunology and Allergy ,Medicine ,VLAG ,business.industry ,medicine.disease ,Obesity ,Editorial ,inflammation ,medicine.symptom ,Colorectal Neoplasms ,lcsh:RC581-607 ,diet ,dietary factors ,business - Published
- 2019
21. Immune Dysfunctions and Immunotherapy in Colorectal Cancer: The Role of Dendritic Cells
- Author
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Filippo Belardelli and Sandra Gessani
- Subjects
0301 basic medicine ,Cancer Research ,Colorectal cancer ,medicine.medical_treatment ,Inflammation ,colorectal cancer ,Review ,Malignancy ,lcsh:RC254-282 ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cancer immunotherapy ,Immunity ,Medicine ,risk factors ,dendritic cells ,business.industry ,pathogenesis ,Immunotherapy ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,immunotherapy ,medicine.symptom ,business - Abstract
Colorectal cancer (CRC), a multi-step malignancy showing increasing incidence in today’s societies, represents an important worldwide health issue. Exogenous factors, such as lifestyle, diet, nutrition, environment and microbiota, contribute to CRC pathogenesis, also influencing non neoplastic cells, including immune cells. Several immune dysfunctions were described in CRC patients at different disease stages. Many studies underline the role of microbiota, obesity-related inflammation, diet and host reactive cells, including dendritic cells (DC), in CRC pathogenesis. Here, we focused on DC, the main cells linking innate and adaptive anti-cancer immunity. Variations in the number and phenotype of circulating and tumor-infiltrating DC have been found in CRC patients and correlated with disease stages and progression. A critical review of DC-based clinical studies and of recent advances in cancer immunotherapy leads to consider new strategies for combining DC vaccination strategies with check-point inhibitors, thus opening perspectives for a more effective management of this neoplastic disease.
- Published
- 2019
22. Dual requirement for STAT signaling in dendritic cell immunobiology
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Gloria Donninelli, Cristina Purificato, Isabella Sanseverino, Maria Cristina Gauzzi, and Sandra Gessani
- Subjects
Lipopolysaccharides ,STAT3 Transcription Factor ,0301 basic medicine ,T-Lymphocytes ,medicine.medical_treatment ,Immunology ,Anti-Inflammatory Agents ,Immunoglobulins ,Biology ,Lymphocyte Activation ,stat ,Immunophenotyping ,Proinflammatory cytokine ,Small Molecule Libraries ,03 medical and health sciences ,Antigens, CD ,Neoplasms ,medicine ,Humans ,Immunology and Allergy ,STAT1 ,Phosphorylation ,STAT2 ,Cells, Cultured ,Membrane Glycoproteins ,Cell Differentiation ,Dendritic Cells ,Hematology ,Dendritic cell ,Cyclic S-Oxides ,Cell biology ,030104 developmental biology ,Cytokine ,biology.protein ,Cytokines ,Signal transduction ,Cell activation ,Signal Transduction - Abstract
Dendritic cells (DC) represent an attractive target for therapeutic manipulation of the immune system and enhancement of insufficient immune response in cancer. STAT family members play key roles in the differentiation and activation of DC, a feature that is currently being exploited in DC-based therapies. We previously reported that the small-molecule Stattic, originally developed as a STAT3-specific inhibitor, also inhibits STAT1 and STAT2 phosphorylation in DC exposed to cytokines or LPS. Aim of this study was to investigate the functional consequences of in vitro treatment with Stattic on DC immunobiology. Interestingly, we observed an opposite effect of Stattic on DC immunophenotype depending on the activation state. While the expression of costimulatory, coinhibitory, MHC class II and CD83 molecules was enhanced in immature DC exposed to Stattic, the LPS induced up-modulation of these molecules was strongly repressed. An effective blockade of LPS-induced secretion of proinflammatory cytokines and capacity to stimulate a Th1 polarization was also observed in the presence of Stattic. Our results indicate that the immunological consequences of STAT inhibition in DC vary depending on the cell activation state. This knowledge is of relevance for anticipating potential effects of STAT-targeted therapeutics, and pursuing selective DC manipulation in clinical applications.
- Published
- 2018
23. Dietary fatty acids and adipose tissue inflammation at the crossroad between obesity and colorectal cancer
- Author
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Sandra Gessani, Beatrice Scazzocchio, Massimo D'Archivio, Rosaria Varì, Lucia Conti, Roberta Masella, Barbara Varano, and Manuela Del Cornò
- Subjects
medicine.medical_specialty ,Colorectal cancer ,business.industry ,Adipose tissue ,Inflammation ,medicine.disease ,Obesity ,Endocrinology ,Oncology ,Weight loss ,Internal medicine ,medicine ,medicine.symptom ,business - Published
- 2019
24. PearlsOy-sters: Paroxysmal dysarthria-ataxia syndrome: Acoustic analysis in a case of antiphospholipid syndrome
- Author
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Maria Teresa Mascia, Carla Budriesi, Sara Contardi, Giada Giovannini, Francesco Cavallieri, Jessica Mandrioli, Annalisa Gessani, Marcella Malagoli, and Elisabetta Zucchi
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Ataxia ,Audiology ,Speech Acoustics ,Loudness ,03 medical and health sciences ,Dysarthria ,0302 clinical medicine ,Antiphospholipid syndrome ,medicine ,Humans ,030212 general & internal medicine ,business.industry ,Brain ,Acoustics ,Middle Aged ,medicine.disease ,Dysarthric speech ,Antiphospholipid Syndrome ,Magnetic Resonance Imaging ,Slow speech ,Female ,Neurology (clinical) ,medicine.symptom ,Isoelectric Focusing ,business ,030217 neurology & neurosurgery - Abstract
Paroxysmal dysarthria-ataxia syndrome (PDA), first described by Parker in 1946, is characterized by paroxysmal and stereotyped repeated daily episodes of sudden ataxic symptoms associated with dysarthric speech lasting from few seconds to minutes.1 During the episodes, patients present with slow speech, irregular articulatory breakdown, dysprosodia, hypernasality, variable pitch and loudness, and prolonged intervals, consistent with perceptual characteristics of ataxic dysarthria.2,3
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- 2019
25. Epigenetic Modifications Induced by Nutrients in Early Life Phases: Gender Differences in Metabolic Alteration in Adulthood
- Author
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Silvia Migliaccio, Sandra Gessani, Emanuela A. Greco, and Andrea Lenzi
- Subjects
0301 basic medicine ,lcsh:QH426-470 ,Mini Review ,Bioinformatics ,03 medical and health sciences ,0302 clinical medicine ,Nutrient ,Quality of life (healthcare) ,Diabetes mellitus ,medicine ,Genetics ,gender ,Endocrine system ,Epigenetics ,endocrine-disrupting chemicals ,Socioeconomic status ,development ,Genetics (clinical) ,epigenetics ,business.industry ,medicine.disease ,Obesity ,lcsh:Genetics ,030104 developmental biology ,nutrition ,030220 oncology & carcinogenesis ,Molecular Medicine ,business ,Hormone - Abstract
Metabolic chronic diseases, also named noncommunicable diseases (NCDs), are considered multifactorial pathologies, which are dramatically increased during the last decades. Noncommunicable diseases such as cardiovascular diseases, obesity, diabetes mellitus, cancers, and chronic respiratory diseases markedly increase morbidity, mortality, and socioeconomic costs. Moreover, NCDs induce several and complex clinical manifestations that lead to a gradual deterioration of health status and quality of life of affected individuals. Multiple factors are involved in the development and progression of these diseases such as sedentary behavior, smoking, pollution, and unhealthy diet. Indeed, nutrition has a pivotal role in maintaining health, and dietary imbalances represent major determinants favoring chronic diseases through metabolic homeostasis alterations. In particular, it appears that specific nutrients and adequate nutrition are important in all periods of life, but they are essential during specific times in early life such as prenatal and postnatal phases. Indeed, epidemiologic and experimental studies report the deleterious effects of an incorrect nutrition on health status several decades later in life. During the last decade, a growing interest on the possible role of epigenetic mechanisms as link between nutritional imbalances and NCDs development has been observed. Finally, because of the pivotal role of the hormones in fat, carbohydrate, and protein metabolism regulation throughout life, it is expected that any hormonal modification of these processes can imbalance metabolism and fat storage. Therefore, a particular interest to several chemicals able to act as endocrine disruptors has been recently developed. In this review, we will provide an overview and discuss the epigenetic role of some specific nutrients and chemicals in the modulation of physiological and pathological mechanisms.
- Published
- 2019
26. Transcriptome Profiles of Human Visceral Adipocytes in Obesity and Colorectal Cancer Unravel the Effects of Body Mass Index and Polyunsaturated Fatty Acids on Genes and Biological Processes Related to Tumorigenesis
- Author
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Massimo D'Archivio, Rosaria Varì, Chiara Romualdi, Andrea Masotti, Lucia Conti, Enrica Calura, Sandra Gessani, Beatrice Scazzocchio, Manuela Del Cornò, Paolo Martini, and Antonella Baldassarre
- Subjects
lcsh:Immunologic diseases. Allergy ,Adult ,Male ,0301 basic medicine ,obesity ,Carcinogenesis ,Immunology ,Adipose tissue ,body mass index ,colorectal cancer ,Inflammation ,Biology ,adipocyte ,medicine.disease_cause ,RNASeq ,Transcriptome ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Fibrosis ,Adipocyte ,Fatty Acids, Omega-3 ,Adipocytes ,medicine ,Humans ,Immunology and Allergy ,Aged ,Biological Phenomena ,Original Research ,Lipid metabolism ,fatty acid ,transcriptome ,Middle Aged ,Lipid Metabolism ,medicine.disease ,030104 developmental biology ,Adipose Tissue ,chemistry ,Tumor progression ,Fatty Acids, Unsaturated ,Cancer research ,Female ,medicine.symptom ,lcsh:RC581-607 ,Colorectal Neoplasms ,030215 immunology - Abstract
Obesity, a low-grade inflammatory condition, represents a major risk factor for the development of several pathologies including colorectal cancer (CRC). Although the adipose tissue inflammatory state is now recognized as a key player in obesity-associated morbidities, the underlying biological processes are complex and not yet precisely defined. To this end, we analyzed transcriptome profiles of human visceral adipocytes from lean and obese subjects affected or not by CRC by RNA sequencing (n = 6 subjects/category), and validated selected modulated genes by real-time qPCR. We report that obesity and CRC, conditions characterized by the common denominator of inflammation, promote changes in the transcriptional program of adipocytes mostly involving pathways and biological processes linked to extracellular matrix remodeling, and metabolism of pyruvate, lipids and glucose. Interestingly, although the transcriptome of adipocytes shows several alterations that are common to both disorders, some modifications are unique under obesity (e.g., pathways associated with inflammation) and CRC (e.g., TGFβ signaling and extracellular matrix remodeling) and are influenced by the body mass index (e.g., processes related to cell adhesion, angiogenesis, as well as metabolism). Indeed, cancer-induced transcriptional program is deeply affected by obesity, with adipocytes from obese individuals exhibiting a more complex response to the tumor. We also report that in vitro exposure of adipocytes to ω3 and ω6 polyunsaturated fatty acids (PUFA) endowed with either anti- or pro-inflammatory properties, respectively, modulates the expression of genes involved in processes potentially relevant to carcinogenesis, as assessed by real-time qPCR. All together our results suggest that genes involved in pyruvate, glucose and lipid metabolism, fibrosis and inflammation are central in the transcriptional reprogramming of adipocytes occurring in obese and CRC-affected individuals, as well as in their response to PUFA exposure. Moreover, our results indicate that the transcriptional program of adipocytes is strongly influenced by the BMI status in CRC subjects. The dysregulation of these interrelated processes relevant for adipocyte functions may contribute to create more favorable conditions to tumor establishment or favor tumor progression, thus linking obesity and colorectal cancer.
- Published
- 2019
27. High-frequency motor rehabilitation in amyotrophic lateral sclerosis: a randomized clinical trial
- Author
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R. Rizzi, Nicola Fini, Elisabetta Sette, Annalisa Gessani, Elisabetta Zucchi, Carlotta Malagoli, Antonio Fasano, Marco Vinceti, Sergio Buja, Simone Storani, Stefano Cavazza, Tiziana Faccioli, Alena Fiocchi, and Jessica Mandrioli
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Physical exercise ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Quality of life ,law ,Medicine ,Aerobic exercise ,Humans ,Respiratory function ,RC346-429 ,Fatigue ,Research Articles ,Aged ,Aged, 80 and over ,Rehabilitation ,business.industry ,General Neuroscience ,Amyotrophic Lateral Sclerosis ,Middle Aged ,Exercise Therapy ,Clinical trial ,Regimen ,030104 developmental biology ,Physical therapy ,Quality of Life ,Female ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,RC321-571 ,Research Article - Abstract
Objective Exercise may be physically and psychologically important for people with ALS, especially in the earlier stages of the disease, and, as a consequence, current ALS clinical management includes individualized rehabilitation as part of multidisciplinary care because. However, while recent studies focused on which type of exercise is more indicated to ALS patients, there is no evidence at which frequency training sessions should be performed. Methods We performed an assessor blinded randomized clinical trial to investigate the superiority of two different frequencies of exercise on rate of progression in ALS. We enrolled 65 patients in two groups: intensive exercise regimen (IER, five sessions/week) versus usual exercise regimen (UER, two sessions/week). The primary aim was to assess if IER decreased disease progression, measured through Amyotrophic Lateral Sclerosis Functional Rating Scale‐Revised, with respect to UER. Secondary aims included assessment of adverse events, tracheostomy‐free survival, motor and respiratory functions, fatigue, quality of life and caregiver burden. Treatment regimen consisted for both groups of the same kind of exercise including aerobic training, endurance training, stretching or assisted active mobilization, differing for frequency of intervention. Results No significant changes in disease progression were found in patients under IER versus UER. At the end of the study, there were no significant differences between the two groups in survival, respiratory function, time to supporting procedures, and quality of life. Adverse events, fatigue, and caregiver burden were not different between the two treatment regimens. Conclusions Despite some limitations, our trial demonstrated that high‐frequency physical exercise was not superior to UER on ALSFRS‐R scores, motor and respiratory functions, survival, fatigue, and quality of life of ALS patients.
- Published
- 2019
28. Proteostasis and ALS: Protocol for a phase II, randomised, double-blind, placebo-controlled, multicentre clinical trial for colchicine in ALS (Co-ALS)
- Author
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Serena Carra, Annalisa Gessani, Isabella Laura Simone, Vincenzo Silani, Alessandro Provenzani, Maria Rosaria Monsurrò, Cristina Cereda, Valentina Bonetto, Gianni Sorarù, Roberto D'Amico, Vito Giuseppe D'Agostino, Mauro Ceroni, Angelo Poletti, Mario Sabatelli, Valeria Crippa, Elisabetta Zucchi, Nilo Riva, Adriano Chiò, and Jessica Mandrioli
- Subjects
Male ,Oncology ,amyotrophic lateral sclerosis ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Protocol ,Colchicine ,Respiratory function ,Amyotrophic lateral sclerosis ,Heat-Shock Proteins ,Randomized Controlled Trials as Topic ,Motor Neurons ,0303 health sciences ,General Medicine ,Middle Aged ,Riluzole ,DNA-Binding Proteins ,Settore MED/26 - NEUROLOGIA ,Neuroprotective Agents ,Treatment Outcome ,Neurology ,Tolerability ,Disease Progression ,Female ,HSPB8 ,medicine.drug ,Adult ,medicine.medical_specialty ,autophagy ,stress granules ,Placebo ,colchicine ,Young Adult ,03 medical and health sciences ,Clinical Trials, Phase II as Topic ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,HSP20 Heat-Shock Proteins ,Aged ,030304 developmental biology ,business.industry ,medicine.disease ,randomized clinical trial ,Clinical trial ,chemistry ,Proteostasis ,business ,Biomarkers ,030217 neurology & neurosurgery ,Molecular Chaperones - Abstract
IntroductionDisruptions of proteasome and autophagy systems are central events in amyotrophic lateral sclerosis (ALS) and support the urgent need to find therapeutic compounds targeting these processes. The heat shock protein B8 (HSPB8) recognises and promotes the autophagy-mediated removal of misfolded mutant SOD1 and TDP-43 fragments from ALS motor neurons (MNs), as well as aggregating species of dipeptides produced in C9ORF72-related diseases. In ALS-SOD1 mice and in human ALS autopsy specimens, HSPB8 is highly expressed in spinal cord MNs that survive at the end stage of disease. Moreover, the HSPB8–BAG3–HSP70 complex maintains granulostasis, which avoids conversion of dynamic stress granules (SGs) into aggregation-prone assemblies. We will perform a randomised clinical trial (RCT) with colchicine, which enhances the expression of HSPB8 and of several autophagy players, blocking TDP-43 accumulation and exerting crucial activities for MNs function.Methods and analysisColchicine in amyotrophic lateral sclerosis (Co-ALS) is a double-blind, placebo-controlled, multicentre, phase II RCT. ALS patients will be enrolled in three groups (placebo, colchicine 0.01 mg/day and colchicine 0.005 mg/day) of 18 subjects treated with riluzole; treatment will last 30 weeks, and follow-up will last 24 weeks. The primary aim is to assess whether colchicine decreases disease progression as measured by ALS Functional Rating Scale - Revised (ALSFRS-R) at baseline and at treatment end. Secondary aims include assessment of (1) safety and tolerability of Colchicine in patiets with ALS; (2) changes in cellular activity (autophagy, protein aggregation, and SG and exosome secretion) and in biomarkers of disease progression (neurofilaments); (3) survival and respiratory function and (4) quality of life. Preclinical studies with a full assessment of autophagy and neuroinflammation biomarkers in fibroblasts, peripheral blood mononuclear cells and lymphoblasts will be conducted in parallel with clinic assessment to optimise time and resources.Ethics and disseminationThe study protocol was approved by the Ethics Committee of Area Vasta Emilia Nord and by Agenzia Italiana del Farmaco (EUDRACT N.2017-004459-21) based on the Declaration of Helsinki. This research protocol was written without patient involvement. Patients’ association will be involved in disseminating the study design and results. Results will be presented during scientific symposia or published in scientific journals.Trial registration numberEUDRACT 2017-004459-21;NCT03693781; Pre-results.
- Published
- 2019
29. Spasmodic dysphonia as a presenting symptom of spinocerebellar ataxia type 12
- Author
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Elisa Sarto, Jessica Rossi, Giada Giovannini, Carla Budriesi, Annalisa Gessani, Stefano Meletti, Sara Contardi, Jessica Mandrioli, Francesco Cavallieri, Miryam Carecchio, and Daniela Di Bella
- Subjects
0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Heterozygote ,Ataxia ,Disease onset ,Spasmodic dysphonia ,Neurodegenerative ,Laryngeal Diseases ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Tremor ,Acoustic analysis ,otorhinolaryngologic diseases ,Genetics ,medicine ,Humans ,Spinocerebellar Ataxias ,Dystonic tremor ,Laryngeal dystonia ,Genetics (clinical) ,Alleles ,Gait Disorders, Neurologic ,Dystonia ,SCA12 ,business.industry ,Brain ,Middle Aged ,medicine.disease ,Dysphonia ,Action tremor ,Dermatology ,Magnetic Resonance Imaging ,nervous system diseases ,030104 developmental biology ,Phenotype ,Dystonic Disorders ,Spinocerebellar ataxia ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Autosomal dominant spinocerebellar ataxia (SCA) type 12 is a rare SCA characterized by a heterogeneous phenotype. Action tremor of the upper limbs is the most common presenting sign and cerebellar signs can appear subsequently. In many cases, minor signs, like dystonia, can be predominant even at onset. Laryngeal dystonia (spasmodic dysphonia) has been observed only in one case of SCA12 and never reported at disease onset. We present a 61-year-old female who developed spasmodic dysphonia followed by dystonic tremor and subsequent ataxia diagnosed with SCA12. Thus, spasmodic dysphonia can be a presenting symptom of SCA12.
- Published
- 2019
30. Editorial: diet, inflammation and colorectal cancer
- Author
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Gessani, S. (Sandra), Van-Duijnhoven, F.J. (Fränzel J.), and Moreno-Aliaga, M. J. (María Jesús)
- Subjects
Oligosaccharides ,Polyphenols ,Body weight ,Polyunsaturated fatty acids (PUFA) - Abstract
This Research Topic was designed to provide the reader with an overview of the impact of body weight and adiposity, as well as of specific food compounds on the inflammatory status in health and disease states, such as CRC. We collected original and review articles featuring the role of specific food compounds in the regulation of immune response and their potential therapeutic implications, the effect of polyunsaturated fatty acids (PUFA), oligosaccharides, polyphenols and body weight in the modulation of inflammation and long-term disease outcomes, highlighting the link between diet, inflammation, and CRC.
- Published
- 2019
31. Innate Lymphocytes in Adipose Tissue Homeostasis and Their Alterations in Obesity and Colorectal Cancer
- Author
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Sandra Gessani, Lucia Conti, and Manuela Del Cornò
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,obesity ,Colorectal cancer ,Mini Review ,Immunology ,Adipose tissue ,Inflammation ,colorectal cancer ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Adipocytes ,Tumor Microenvironment ,Immunology and Allergy ,Homeostasis ,Humans ,Lymphocytes ,Tissue homeostasis ,business.industry ,Cancer ,immune profile ,medicine.disease ,Immunity, Innate ,adipose tissue ,030104 developmental biology ,Cancer cell ,Cancer research ,medicine.symptom ,business ,Carcinogenesis ,Colorectal Neoplasms ,lcsh:RC581-607 ,innate lymphocytes ,030215 immunology - Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide and a leading cause of death, with burden expected to increase in the coming years. Enhanced adiposity, particularly visceral fat, is associated with increased cancer incidence representing an important indicator of survival, prognosis, recurrence rates, and response to therapy for several tumors including CRC. Compelling evidence has been achieved that the low-grade chronic inflammation characterizing obesity represents a main factor that can favor carcinogenesis. Adipocytes and adipose tissue (AT) infiltrating immune cells contribute to obesity-related inflammation by releasing soluble factors affecting, both locally and systemically, the function of several cell types, including immune and cancer cells. The unbalanced production of immune mediators as well as the profound changes in the repertoire and activation state of immune cells in AT of obese subjects represent key events in the processes that set the basis for a pro-tumorigenic microenvironment. AT harbors a unique profile of immune cells of different origin that play an important role in tissue homeostasis. Among these, tissue-resident innate lymphocytes are emerging as important AT components whose depletion/aberrant activation occurring in obesity could have an impact on inflammation and immune-surveillance against tumors. However, a direct link between obesity-induced dysfunction and cancer development has not been demonstrated yet. In this review, we provide an overview of human obesity- and CRC-induced alterations of blood and adipose tissue-associated innate lymphocytes, and discuss how the adipose tissue microenvironment in obesity might influence the development of CRC.
- Published
- 2018
32. G-CSF (filgrastim) treatment for amyotrophic lateral sclerosis: protocol for a phase II randomised, double-blind, placebo-controlled, parallel group, multicentre clinical study (STEMALS-II trial)
- Author
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Adriano Chiò, Christian Lunetta, Federico Casale, Letizia Mazzini, Andrea Calvo, Cristina Moglia, Jessica Mandrioli, Isabella Laura Simone, Giuseppe Fuda, Paolina Salamone, Giuseppe Marrali, Claudia Caponnetto, Vincenzo La Bella, Corrado Tarella, A Bombaci, M Brunetti, S Cammarosano, A Canosa, C Calvo, M Daviddi, G De Marco, P Cugnasco, M Grassano, B Iazzolino, A Ilardi, C Lauritano, A Lomartire, U Manera, L Solero, MC Torrieri, R Vasta, M Gilestro, VE Muccio, P Omedé, F Gerardi, C Cabona, G Novi, E Bersano, F De Marchi, R Spataro, R. Scimè, A Fasano, N Fini, A Gessani, E D’Errico, A Scarafino, and la bella vincenzo
- Subjects
Oncology ,amyotrophic lateral sclerosis ,medicine.medical_specialty ,Filgrastim ,Placebo ,cGSF, ALS, Clinical trial ,law.invention ,randomised clinical trial ,Clinical Trials, Phase II as Topic ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Multicenter Studies as Topic ,Amyotrophic lateral sclerosis ,Randomized Controlled Trials as Topic ,business.industry ,General Medicine ,GCS-F ,haematopoietic stem cells ,medicine.disease ,Granulocyte colony-stimulating factor ,Transplantation ,Clinical trial ,Neurology ,Italy ,Tolerability ,Quality of Life ,Medicine ,Settore MED/26 - Neurologia ,business ,medicine.drug - Abstract
IntroductionAmyotrophic lateral sclerosis (ALS) is a fatal progressive neurological disorder characterised by a selective degeneration of motor neurons (MNs). Stem cell transplantation is considered as a promising strategy in neurological disorders therapy and the possibility of inducing bone marrow cells (BMCs) to circulate in the peripheral blood is suggested to investigate stem cells migration in degenerated ALS nerve tissues where potentially repair MN damage. Granulocyte-colony stimulating factor (G-CSF) is a growth factor which stimulates haematopoietic progenitor cells, mobilises BMCs into injured brain and it is itself a neurotrophic factor for MN. G-CSF safety in humans has been demonstrated and many observations suggest that it may affect neural cells. Therefore, we decided to use G-CSF to mobilise BMCs into the peripheral circulation in patients with ALS, planning a clinical trial to evaluate the effect of G-CSF administration in ALS patients compared with placebo.Methods and analysisSTEMALS-II is a phase II multicentre, randomised double-blind, placebo-controlled, parallel group clinical trial on G-CSF (filgrastim) and mannitol in ALS patients. Specifically, we investigate safety, tolerability and efficacy of four repeated courses of intravenous G-CSF and mannitol administered in 76 ALS patients in comparison with placebo (indistinguishable glucose solution 5%). We determine increase of G-CSF levels in serum and cerebrospinal fluid as CD34+cells and leucocyte count after treatment; reduction in ALS Functional Rating Scale-Revised Score, forced vital capacity, Scale for Testing Muscle Strength Score and quality of life; the adverse events/reactions during the treatment; changes in neuroinflammation biomarkers before and after treatment.Ethics and disseminationThe study protocol was approved by the Ethics Committee of Azienda Ospedaliera Universitaria ‘Città della Salute e della Scienza’, Torino, Italy. Results will be presented during scientific symposia or published in scientific journals.Trial registration numberEudract 2014-002228-28.
- Published
- 2020
33. Revisiting the impact of lifestyle on colorectal cancer risk in a gender perspective
- Author
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Manuela Del Cornò, Sandra Gessani, and Lucia Conti
- Subjects
Male ,0301 basic medicine ,Colorectal cancer ,Physical activity ,Overweight ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Risk Factors ,Environmental health ,Humans ,Medicine ,Obesity ,Risk factor ,Life Style ,business.industry ,Incidence (epidemiology) ,Cancer ,Feeding Behavior ,Hematology ,medicine.disease ,digestive system diseases ,Diet ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Etiology ,Female ,medicine.symptom ,Colorectal Neoplasms ,business - Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related mortality in the world. Patterns and trends in CRC incidence and mortality correlate with increasing adoption of Western lifestyles and with the overweight/obesity epidemic. Both genetic background and a range of modifiable environmental/lifestyle factors play a role in CRC etiology. Among these the links of body weight, dietary patterns and physical activity (PA) behavior with CRC risk are some of the strongest for any type of cancer, with a different impact in women and men. Nonetheless, gender disparities still represent a neglected aspect of CRC management. This review sheds light on gender-related association of obesity and different dietary/PA habits with CRC risk, highlighting the importance of lifestyle modifications in the prevention of this neoplastic disease. In this scenario, intervention studies are strongly recommended to define the most effective dietary/PA regimens for primary prevention of cancer in women and men.
- Published
- 2020
34. Rapamycin treatment for amyotrophic lateral sclerosis
- Author
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Mandrioli, Jessica, D’Amico, Roberto, Zucchi, Elisabetta, Gessani, Annalisa, Fini, Nicola, Fasano, Antonio, Caponnetto, Claudia, Chiò, Adriano, Dalla Bella, Eleonora, Lunetta, Christian, Mazzini, Letizia, Marinou, Kalliopi, Sorarù, Gianni, de Biasi, Sara, Lo Tartaro, Domenico, Pinti, Marcello, and Cossarizza, Andrea
- Subjects
Sirolimus ,amyotrophic lateral sclerosis ,autophagy ,TOR Serine-Threonine Kinases ,randomized clinical trial ,Survival Rate ,Treatment Outcome ,Double-Blind Method ,Italy ,Study Protocol Clinical Trial ,Research Design ,Treg lymphocytes ,Quality of Life ,Humans ,Rapamycin ,Biomarkers ,Immunosuppressive Agents ,Research Article - Abstract
Introduction: Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients. Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients. Methods: RAP-ALS is a phase II randomized, double-blind, placebo-controlled, multicenter (8 ALS centers in Italy), clinical trial. The primary aim is to assess whether Rapamycin administration increases Tregs number in treated patients compared with control arm. Secondary aims include the assessment of safety and tolerability of Rapamycin in patients with ALS; the minimum dosage to have Rapamycin in cerebrospinal fluid; changes in immunological (activation and homing of T, B, NK cell subpopulations) and inflammatory markers, and on mTOR downstream pathway (S6RP phosphorylation); clinical activity (ALS Functional Rating Scale-Revised, survival, forced vital capacity); and quality of life (ALSAQ40 scale). Discussion: Rapamycin potentially targets mechanisms at play in ALS (i.e., autophagy and neuroinflammation), with promising preclinical studies. It is an already approved drug, with known pharmacokinetics, already available and therefore with significant possibility of rapid translation to daily clinics. Findings will provide reliable data for further potential trials. Ethics and dissemination: The study protocol was approved by the Ethics Committee of Azienda Ospedaliero Universitaria of Modena and by the Ethics Committees of participating centers (Eudract n. 2016-002399-28) based on the Helsinki declaration.
- Published
- 2018
35. Rapamycin treatment for amyotrophic lateral sclerosis protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial)
- Author
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Mandrioli, J., D'Amico, R., Zucchi, E., Gessani, A., Fini, N., Fasano, A., Caponnetto, C., Chio, A., Bella, E. D., Lunetta, C., Mazzini, L., Marinou, K., Soraru, G., De Biasi, S., Lo Tartaro, D., Pinti, M., Nichelli, P., Vicini, R., Cabona, C., Calvo, A., Moglia, C., Manera, U., Fuda, G., Canosa, A., Ilardi, A., Lauria, G., Dalla Bella, E., Gerardi, F., Scognamiglio, A., De Marchi, F., Mora, G., Gizzi, M., and Cossarizza, A.
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,amyotrophic lateral sclerosis ,autophagy ,Helsinki declaration ,law.invention ,03 medical and health sciences ,Randomized controlled trial ,Double-Blind Method ,law ,Internal medicine ,medicine ,Humans ,Rapamycin ,Amyotrophic lateral sclerosis ,Mechanistic target of rapamycin ,Sirolimus ,biology ,business.industry ,TOR Serine-Threonine Kinases ,Medicine (all) ,General Medicine ,medicine.disease ,randomized clinical trial ,Clinical trial ,Survival Rate ,030104 developmental biology ,Treg lymphocytes ,Amyotrophic Lateral Sclerosis ,Biomarkers ,Immunosuppressive Agents ,Italy ,Quality of Life ,Research Design ,Treatment Outcome ,Tolerability ,biology.protein ,business ,Autophagy ,Randomized clinical trial ,medicine.drug - Abstract
Introduction Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients.Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients. Methods RAP-ALS is a phase II randomized, double-blind, placebo-controlled, multicenter (8 ALS centers in Italy), clinical trial. The primary aim is to assess whether Rapamycin administration increases Tregs number in treated patients compared with control arm. Secondary aims include the assessment of safety and tolerability of Rapamycin in patients with ALS; the minimum dosage to have Rapamycin in cerebrospinal fluid; changes in immunological (activation and homing of T, B, NK cell subpopulations) and inflammatory markers, and on mTOR downstream pathway (S6RP phosphorylation); clinical activity (ALS Functional Rating Scale-Revised, survival, forced vital capacity); and quality of life (ALSAQ40 scale). Discussion Rapamycin potentially targets mechanisms at play in ALS (i.e., autophagy and neuroinflammation), with promising preclinical studies. It is an already approved drug, with known pharmacokinetics, already available and therefore with significant possibility of rapid translation to daily clinics. Findings will provide reliable data for further potential trials. Ethics and dissemination The study protocol was approved by the Ethics Committee of Azienda Ospedaliero Universitaria of Modena and by the Ethics Committees of participating centers (Eudract n. 2016-002399-28) based on the Helsinki declaration.
- Published
- 2018
36. Cerebrospinal Fluid Neurofilaments May Discriminate Upper Motor Neuron Syndromes: A Pilot Study
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Nicola Fini, Roberta Bedin, Jessica Mandrioli, Elisabetta Zucchi, Marco Vinceti, Annalisa Gessani, and Antonio Fasano
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Hereditary spastic paraplegia ,Intermediate Filaments ,Pilot Projects ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Amyotrophic lateral sclerosis ,Hereditary spastic paraparesis ,Neurofilaments ,Upper motor neuron ,Neurofilament Proteins ,Internal medicine ,medicine ,Humans ,Motor Neuron Disease ,Survival analysis ,Aged ,Primary Lateral Sclerosis ,Motor Neurons ,Receiver operating characteristic ,business.industry ,Amyotrophic Lateral Sclerosis ,Area under the curve ,Middle Aged ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Disease Progression ,Female ,Neurology (clinical) ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Background: Patients presenting with upper motor neuron (UMN) signs may widely diverge in prognosis, ranging from amyotrophic lateral sclerosis (ALS) to primary lateral sclerosis (PLS) and hereditary spastic paraplegia (hSP). Neurofilaments are emerging as potential diagnostic and prognostic biomarkers for ALS, but the diagnosis of UMN syndromes still relies mostly on clinical long-term observation and on familiarity or genetic confirmation. Objectives: To test whether phosphorylated neurofilament heavy chain (pNfH) may discriminate different UMN syndromes at diagnosis and to test their prognostic role among these diseases. Methods: We measured the cerebrospinal fluid (CSF) and serum pNfH of 30 patients presenting with UMN signs and diagnosed with ALS, hSP, and PLS, plus 9 healthy controls (HC). Results: ALS patients had higher levels of pNfH in CSF and serum compared to HC (p < 0.001 and p < 0.001 in CSF and serum, respectively) and PLS (p = 0.015 and p = 0.038) and hSP (p = 0.003 and p = 0.001) patients. PLS and hSP patients had similar CSF and serum pNfH concentrations, but a higher CSF pNfH concentration, compared to HC (p = 0.002 and p = 0.003 for PLS and hSP, respectively). Receiver operating characteristic curves for discriminating ALS from PLS and hSP showed an area under the curve of 0.79 for CSF and 0.81 for serum. In multivariable survival analysis including relevant clinical factors CSF pNfH represented the strongest variable predicting survival (HR 40.43; 95% CI 3.49–467.79, p = 0.003) independently of clinical group. Conclusions: Despite some statistical instability of the results due to limitations in sample size, our study supports the role of CSF pNfH as a prognostic biomarker for motor neuron diseases presenting with UMN signs. A potential power to discriminate between ALS and other UMN syndromes at presentation, and between all of the examined MND and HC, has been detected for both CSF and serum pNfH.
- Published
- 2018
37. Pigmenti bicomponenti in un inchiostro verde per tatuaggi: determinazione chimica, spettrofotometrica e microscopica
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Laureanda: Gessani Flavia, Relatore: Dr.ssa Marilena Carbone, and Dr.ssa Elvira Maria Bauer
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pigmenti ,inchiostro per tatuaggi - Abstract
Tesi di Laurea in Chimica riguardante l'analisi spettrofotometrica e morfologica dei pigmenti contenuti in un inchiostro verde per tatuaggi
- Published
- 2018
38. Direct and Intestinal Epithelial Cell-Mediated Effects of TLR8 Triggering on Human Dendritic Cells, CD14+CD16+ Monocytes and γδ T Lymphocytes
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Costanza Angelini, Barbara Varano, Patrizia Puddu, Maurizio Fiori, Antonella Baldassarre, Andrea Masotti, Sandra Gessani, and Lucia Conti
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0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Innate immune system ,Chemistry ,Monocyte ,Gamma/Delta T-Lymphocyte ,CD14 ,Immunology ,Intestinal epithelium ,microenvironment ,Cell biology ,cell activation ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Immune system ,adjuvant ,inflammation ,Monocyte differentiation ,medicine ,Immunology and Allergy ,pathogen recognition ,Cell activation ,lcsh:RC581-607 - Abstract
Toll-like receptor (TLR)7/8 plays a crucial role in host recognition/response to viruses and its mucosal expression directly correlates with intestinal inflammation. The aim of this study was to investigate the role of TLR7/8 stimulation of intestinal epithelium in shaping the phenotype and functions of innate immunity cell subsets, and to define direct and/or epithelial cell-mediated mechanisms of the TLR7/8 agonist R848 immunomodulatory activity. We describe novel, TLR8-mediated, pro- and anti-inflammatory effects of R848 on ex-vivo cultured human blood monocytes and gamma delta T lymphocytes, either induced by direct immune cell stimulation or mediated by intestinal epithelial cells. Apical stimulation with R848 led to its transport across normal polarized epithelial cell monolayer and resulted in the inhibition of monocyte differentiation toward immunostimulatory dendritic cells and Th1-type response. Furthermore, gamma delta T lymphocyte activation was promoted following direct exposure of these cells to the agonist. Conversely, a selective enrichment of the CD14+CD16+ monocyte subpopulation was observed, which required a CCL2-mediated inflammatory response of normal epithelial cells to R848. Of note, a TLR-mediated activation of control gamma delta T lymphocytes was promoted by inflamed intestinal epithelium from active Crohn’s disease patients. This study unravels a novel regulatory mechanism linking the activation of the TLR8 pathway in intestinal epithelial cells to the monocyte-mediated inflammatory response, and highlights the capacity of the TLR7/8 agonist R848 to directly enhance the activation of gamma delta T lymphocytes. Overall these results expand the range of cell targets and immune responses controlled by TLR8 triggering that may contribute to the antiviral response, to chronic inflammation, as well as to the adjuvant activity of TLR8 agonists, highlighting the role of intestinal epithelium microenvironment in shaping TLR agonist-induced responses.
- Published
- 2017
39. Interplay between HIV-1 and Toll-like receptors in human myeloid cells: friend or foe in HIV-1 pathogenesis?
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Gloria Donninelli, Sandra Gessani, and Manuela Del Cornò
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0301 basic medicine ,Viral pathogenesis ,Immunology ,Antigen presentation ,HIV Infections ,Immune receptor ,Biology ,Ligands ,Virus Replication ,Innate immunity ,Pathogen recognition ,Cell Biology ,Viral Proteins ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Humans ,Immunology and Allergy ,Myeloid Cells ,Receptor ,Antigens, Viral ,Antigen Presentation ,Innate immune system ,Toll-Like Receptors ,Acquired immune system ,Immunity, Innate ,Cell biology ,030104 developmental biology ,Viral replication ,Host-Pathogen Interactions ,HIV-1 ,Receptors, Chemokine ,Protein Binding ,030215 immunology - Abstract
The Toll-like receptors are the first line of the host response to pathogens, representing an essential component of the innate and adaptive immune response. They recognize different pathogens and trigger responses directed at eliminating the invader and at developing immunologic long-term memory, ultimately affecting viral pathogenesis. In viral infections, sensing of nucleic acids and/or viral structural proteins generally induces a protective immune response. Thus, it is not surprising that many viruses have developed strategies to evade or counteract signaling through the Toll-like receptor pathways, to survive the host defense machinery and ensure propagation. Thus, Toll-like receptor engagement can also be part of viral pathogenic mechanisms. Evidence for a direct interaction of Toll-like receptors with human immunodeficiency virus type 1 (HIV-1) structures has started to be achieved, and alterations of their expression and function have been described in HIV-1–positive subjects. Furthermore, Toll-like receptor triggering by bacterial and viral ligands have been described to modulate HIV-1 replication and host response, leading to protective or detrimental effects. This review covers major advances in the field of HIV-1 interplay with Toll-like receptors, focusing on human myeloid cells (e.g., monocytes/macrophages and dendritic cells). The role of this interaction in the dysregulation of myeloid cell function and in dictating aspects of the multifaceted pathogenesis of acquired immunodeficiency syndrome will be discussed.
- Published
- 2015
40. Bovine Lactoferrin-Induced CCL1 Expression Involves Distinct Receptors in Monocyte-Derived Dendritic Cells and Their Monocyte Precursors
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Manuela Del Cornò, Gabriella Rainaldi, Barbara Varano, Lucia Conti, Patrizia Puddu, Sandra Gessani, Laura Fantuzzi, Daniela Angela Covino, Daniela Latorre, Nadia Pulvirenti, Gloria Donninelli, Maria Cristina Gauzzi, Michela Sabbatucci, Cristina Purificato, Latorre, D, Pulvirenti, N, Covino, D, Varano, B, Purificato, C, Rainaldi, G, Gauzzi, M, Fantuzzi, L, Conti, L, Donninelli, G, Del Corno, M, Sabbatucci, M, Gessani, S, and Puddu, P
- Subjects
Surface receptor ,Cell type ,monocyte ,dendritic cell ,lactoferrin ,CCL1 ,surface receptors ,Health, Toxicology and Mutagenesis ,lcsh:Medicine ,Toxicology ,Article ,Monocytes ,Chemokine CCL1 ,medicine ,Animals ,Humans ,Secretion ,RNA, Messenger ,Receptor ,Cells, Cultured ,Chemistry ,Monocyte ,lcsh:R ,Dendritic Cells ,Dendritic cell ,Cell biology ,medicine.anatomical_structure ,Chemokine secretion ,Cattle - Abstract
Lactoferrin (LF) exhibits a wide range of immunomodulatory activities including modulation of cytokine and chemokine secretion. In this study, we demonstrate that bovine LF (bLF) up-modulates, in a concentration- and time-dependent manner, CCL1 secretion in monocytes (Mo) at the early stage of differentiation toward dendritic cells (DCs), and in fully differentiated immature Mo-derived DCs (MoDCs). In both cell types, up-modulation of CCL1 secretion is an early event following bLF-mediated enhanced accumulation of CCL1 transcripts. Notably, bLF-mediated up-regulation of CCL1 involves the engagement of distinct surface receptors in MoDCs and their Mo precursors. We show that bLF-mediated engagement of CD36 contributes to CCL1 induction in differentiating Mo. Conversely, toll-like receptor (TLR)2 blocking markedly reduces bLF-induced CCL1 production in MoDCs. These findings add further evidence for cell-specific differential responses elicited by bLF through the engagement of distinct TLRs and surface receptor. Furthermore, the different responses observed at early and late stages of Mo differentiation towards DCs may be relevant in mediating bLF effects in specific body districts, where these cell types may be differently represented in physiopathological conditions.
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- 2015
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41. Direct and Intestinal Epithelial Cell-Mediated Effects of TLR8 Triggering on Human Dendritic Cells, CD14
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Costanza, Angelini, Barbara, Varano, Patrizia, Puddu, Maurizio, Fiori, Antonella, Baldassarre, Andrea, Masotti, Sandra, Gessani, and Lucia, Conti
- Subjects
adjuvant ,inflammation ,Immunology ,pathogen recognition ,microenvironment ,Original Research ,cell activation - Abstract
Toll-like receptor (TLR)7/8 plays a crucial role in host recognition/response to viruses and its mucosal expression directly correlates with intestinal inflammation. The aim of this study was to investigate the role of TLR7/8 stimulation of intestinal epithelium in shaping the phenotype and functions of innate immunity cell subsets, and to define direct and/or epithelial cell-mediated mechanisms of the TLR7/8 agonist R848 immunomodulatory activity. We describe novel, TLR8-mediated, pro- and anti-inflammatory effects of R848 on ex vivo cultured human blood monocytes and γδ T lymphocytes, either induced by direct immune cell stimulation or mediated by intestinal epithelial cells (IEC). Apical stimulation with R848 led to its transport across normal polarized epithelial cell monolayer and resulted in the inhibition of monocyte differentiation toward immunostimulatory dendritic cells and Th1 type response. Furthermore, γδ T lymphocyte activation was promoted following direct exposure of these cells to the agonist. Conversely, a selective enrichment of the CD14+CD16+ monocyte subpopulation was observed, which required a CCL2-mediated inflammatory response of normal epithelial cells to R848. Of note, a TLR-mediated activation of control γδ T lymphocytes was promoted by inflamed intestinal epithelium from active Crohn’s disease patients. This study unravels a novel regulatory mechanism linking the activation of the TLR8 pathway in IEC to the monocyte-mediated inflammatory response, and highlights the capacity of the TLR7/8 agonist R848 to directly enhance the activation of γδ T lymphocytes. Overall these results expand the range of cell targets and immune responses controlled by TLR8 triggering that may contribute to the antiviral response, to chronic inflammation, as well as to the adjuvant activity of TLR8 agonists, highlighting the role of intestinal epithelium microenvironment in shaping TLR agonist-induced responses.
- Published
- 2017
42. [P3–514]: NAMING IMPROVEMENT IN PRIMARY PROGRESSIVE APHASIA FOLLOWING LEXICAL TRAINING
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Paolo Frigio Nichelli, Annalisa Gessani, Manuela Tondelli, Annalisa Chiari, Chiara Vincenzi, Giovanna Zamboni, Carla Budriesi, and Gloria Bimbi
- Subjects
medicine.medical_specialty ,Epidemiology ,Health Policy ,Aphasiology ,Audiology ,medicine.disease ,Primary progressive aphasia ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,Psychology - Published
- 2017
43. Linking Diet to Colorectal Cancer: The Emerging Role of MicroRNA in the Communication between Plant and Animal Kingdoms
- Author
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Sandra Gessani, Manuela Del Cornò, Lucia Conti, and Gloria Donninelli
- Subjects
0301 basic medicine ,Microbiology (medical) ,Colorectal cancer ,Mini Review ,inter kingdom communication ,epigenetic mechanisms ,Inflammation ,colorectal cancer ,Biology ,Bioinformatics ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,medicine ,Food components ,Cancer ,medicine.disease ,Non-coding RNA ,Phenotype ,030104 developmental biology ,Lifestyle factors ,030220 oncology & carcinogenesis ,medicine.symptom ,diet ,bioactive food components - Abstract
Environmental and lifestyle factors, including diet and nutritional habits have been strongly linked to colorectal cancer (CRC). Of note, unhealthy dietary habits leading to adiposity represent a main risk factor for CRC and are associated with a chronic low-grade inflammatory status. Inflammation is a hallmark of almost every type of cancer and can be modulated by several food compounds exhibiting either protective or promoting effects. However, in spite of an extensive research, the underlying mechanisms by which dietary patterns or bioactive food components may influence tumor onset and outcome have not been fully clarified yet. Growing evidence indicates that diet, combining beneficial substances and potentially harmful ingredients, has an impact on the expression of key regulators of gene expression such as the non-coding RNA (ncRNA). Since the expression of these molecules is deranged in chronic inflammation and cancer, modulating their expression may strongly influence the cancer phenotype and outcomes. In addition, the recently acquired knowledge on the existence of intricate inter-kingdom communication networks, is opening new avenues for a deeper understanding of the intimate relationships linking diet to CRC. In this novel scenario, diet-modulated ncRNA may represent key actors in the interaction between plant and animal kingdoms, capable of influencing disease onset and outcome. In this review, we will summarize the studies demonstrating a link between bioactive food components, including food-derived, microbiota-processed, secondary metabolites, and host ncRNA. We will focus on microRNA, highlighting how this plant/animal inter-kingdom cross-talk may have an impact on CRC establishment and progression.
- Published
- 2017
44. Distinct blood and visceral adipose tissue regulatory T cell and innate lymphocyte profiles characterize obesity and colorectal cancer
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Gloria Donninelli, Manuela Del Cornò, Marina Pierdominici, Beatrice Scazzocchio, Rosaria Varì, Barbara Varano, Ilenia Pacella, Silvia Piconese, Vincenzo Barnaba, Massimo D’Archivio, Roberta Masella, Lucia Conti, and Sandra Gessani
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,obesity ,regulatory T cell ,Regulatory T cell ,Colorectal cancer ,Lymphocyte ,T cell ,Cell ,Immunology ,Adipose tissue ,Inflammation ,chemical and pharmacologic phenomena ,colorectal cancer ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Immunology and Allergy ,Original Research ,NKT-like cell ,nutritional and metabolic diseases ,immune profile ,medicine.disease ,adipose tissue ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,fatty acid ,medicine.symptom ,γδ T lymphocyte ,lcsh:RC581-607 ,Fatty acid ,Immune profile ,Obesity - Abstract
Visceral adipose tissue (VAT) is a main site where metabolic and immunologic processes interplay to regulate, at local and systemic level, the inflammatory status and immune response. Obesity-associated inflammation and immune dysfunctions are inextricably linked to tumor but, in spite of intense efforts, the mechanisms underpinning this association remain elusive. In this report, we characterized the profile of VAT-associated and circulating innate lymphocyte and regulatory T (Treg) cell subsets underlying inflammatory conditions, such as obesity and colorectal cancer (CRC). Analysis of NK, NKT-like, γδ T, and Treg cell populations in VAT and blood of healthy lean subjects revealed that CD56hi NK and OX40+ Treg cells are more abundant in VAT with respect to blood. Conversely, CD56dim NK and total Treg cells are most present in the circulation, while γδ T lymphocytes are uniformly distributed in the two compartments. Interestingly, a reduced frequency of circulating activated Treg cells, and a concomitant preferential enrichment of OX40-expressing Treg cells in VAT, were selectively observed in obese (Ob) subjects, and directly correlated with body mass index. Likewise, CRC patients were characterized by a specific enrichment of VAT-associated NKT-like cells. In addition, Ob and CRC-affected individuals shared a significant reduction of the Vγ9Vδ2/γδ T cell ratio at systemic level. The alterations in the relative proportions of Treg and NKT-like cells in VAT were found to correlate with the content of pro- and anti-inflammatory polyunsaturated fatty acids (PUFA), respectively. Overall, these results provide evidence for distinct alterations of the immune cell repertoire in the periphery with respect to the VAT microenvironment that uniquely characterize or are shared by different inflammatory conditions, such as obesity and CRC, and suggest that VAT PUFA composition may represent one of the factors that contribute to shape the immune phenotypes.
- Published
- 2017
45. STAT3-silenced human dendritic cells have an enhanced ability to prime IFNγ production by both αβ and γδ T lymphocytes
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Sandra Gessani, M. Cristina Gauzzi, Isabella Sanseverino, Lucia Conti, Barbara Varano, and Cristina Purificato
- Subjects
CD4-Positive T-Lymphocytes ,STAT3 Transcription Factor ,Chemokine ,Time Factors ,Receptors, Antigen, T-Cell, alpha-beta ,medicine.medical_treatment ,Blotting, Western ,Immunology ,Lymphocyte Activation ,Major histocompatibility complex ,Monocytes ,Interferon-gamma ,Immune system ,T-Lymphocyte Subsets ,medicine ,Humans ,Immunology and Allergy ,Chemokine CCL4 ,Cells, Cultured ,biology ,Toll-Like Receptors ,Cell Differentiation ,Receptors, Antigen, T-Cell, gamma-delta ,Dendritic Cells ,Hematology ,Dendritic cell ,Th1 Cells ,Flow Cytometry ,Interleukin-12 ,Coculture Techniques ,Interleukin 10 ,Cytokine ,biology.protein ,Interleukin 12 ,Cytokines ,RNA Interference ,Cytokine secretion - Abstract
Dendritic cells (DC) are an attractive target for therapeutic manipulation of the immune system to enhance insufficient immune responses, such those occurring in cancer, or to dampen dangerous responses in allergic and autoimmune diseases. Main goal of this study was to manipulate human monocyte-derived DC (MDDC) function by silencing STAT3, since this transcription factor plays a key role as a negative regulator of immune surveillance, and is strongly involved in inflammation. STAT3 silencing did not affect the immunophenotype of both immature and toll-like receptor (TLR) ligand-matured DC. However, an altered cytokine secretion profile, characterized by lower IL10 and higher IL12 and TNFα levels, was observed in silenced DC with respect to control cells upon TLR triggering. Accordingly, STAT3 silenced MDDC promoted a higher IFNγ production by CD4+ naive T cells. Furthermore, STAT3 silencing in MDDC favored the activation of γδ T lymphocytes, an immune cell population with important antitumor effector activities. This effect was at least in part mediated by the increased IL12 production by silenced cells. STAT3 silencing also increased the levels of CCL4, a CCR5-binding chemokine known to be involved in T helper 1 (Th1) cell recruitment. Altogether these results strengthen the role of STAT3 as a critical check point of the suppression of Th1 responses, unraveling its potential to dampen DC capability to both induce and recruit different IFNγ producing T lymphocyte subsets.
- Published
- 2014
46. Regulation of Dendritic Cell Function by Dietary Polyphenols
- Author
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Sandra Gessani, Roberta Masella, Manuela Del Cornò, and Beatrice Scazzocchio
- Subjects
Genetic Markers ,0301 basic medicine ,Biological Availability ,Biology ,Industrial and Manufacturing Engineering ,03 medical and health sciences ,Therapeutic approach ,0302 clinical medicine ,Immune system ,Vegetables ,Global health ,Animals ,Humans ,chemistry.chemical_classification ,Polyphenols ,Cell Differentiation ,Nutritional status ,Dendritic Cells ,General Medicine ,Dendritic cell ,Diet ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Fruit ,Immunology ,Essential nutrient ,Cell activation ,Function (biology) ,030215 immunology ,Food Science - Abstract
Marked changes in socioeconomic status, cultural traditions, population growth, and agriculture have been affecting diets worldwide. Nutrition is known to play a pivotal role in the pathogenesis of several chronic diseases, and the use of bioactive food compounds at pharmacologic doses is emerging as a preventive and/or therapeutic approach to target metabolic dysregulations occurring in aging, obesity-related chronic diseases, and cancer. Only recently have data on the effects of specific nutrients or food on the immune system become available, and studies regarding the human immune system are still in their infancy. Beyond providing essential nutrients, diet can actively influence the immune system. Understanding how diet and nutritional status influence the innate and adaptive arms of our immune system represents an area of scientific need, opportunity, and challenge. The insights gleaned should help to address several pressing global health problems. Recently, biologically active polyphenols, which are widespread constituents of fruit and vegetables, have gained importance as complex regulators of various cellular processes, critically involved in the maintenance of body homeostasis. This review outlines the potential effects of polyphenols on the function of dendritic cells (DCs), key players in the orchestration of the immune response. Their effects on different aspects of DC biology including differentiation, maturation, and DC capacity to shift immune response toward tolerance or immune activation will be outlined.
- Published
- 2014
47. Type I Interferons as Regulators of Human Antigen Presenting Cell Functions
- Author
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Filippo Belardelli, Sandra Gessani, Lucia Conti, and Manuela Del Cornò
- Subjects
Cell type ,dendritic cell ,Health, Toxicology and Mutagenesis ,lcsh:Medicine ,cell differentiation/activation ,Antigen-Presenting Cells ,Review ,Biology ,Adaptive Immunity ,Toxicology ,Immune system ,Immunity ,microRNA ,Animals ,Humans ,transcriptional profile ,Antigen-presenting cell ,Innate lymphoid cell ,lcsh:R ,Models, Immunological ,antigen uptake/processing/presentation ,Dendritic cell ,Acquired immune system ,T cell response ,Immunity, Innate ,Immunology ,Interferon Type I ,type I interferon - Abstract
Type I interferons (IFNs) are pleiotropic cytokines, initially described for their antiviral activity. These cytokines exhibit a long record of clinical use in patients with some types of cancer, viral infections and chronic inflammatory diseases. It is now well established that IFN action mostly relies on their ability to modulate host innate and adaptive immune responses. Work in recent years has begun to elucidate the mechanisms by which type I IFNs modify the immune response, and this is now recognized to be due to effects on multiple cell types, including monocytes, dendritic cells (DCs), NK cells, T and B lymphocytes. An ensemble of results from both animal models and in vitro studies emphasized the key role of type I IFNs in the development and function of DCs, suggesting the existence of a natural alliance between these cytokines and DCs in linking innate to adaptive immunity. The identification of IFN signatures in DCs and their dysregulation under pathological conditions will therefore be pivotal to decipher the complexity of this DC-IFN interaction and to better exploit the therapeutic potential of these cells.
- Published
- 2014
48. ω3 polyunsaturated fatty acids as immunomodulators in colorectal cancer: new potential role in adjuvant therapies
- Author
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Roberta Masella, Anna Maria Mileo, Stefania Miccadei, and Sandra Gessani
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Colorectal cancer ,medicine.medical_treatment ,Mini Review ,Immunology ,Context (language use) ,colorectal cancer ,Bioinformatics ,Immunomodulation ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Adjuvant therapy ,Immunology and Allergy ,chemistry.chemical_classification ,Inflammation ,business.industry ,Cancer ,Inflammasome ,adjuvant therapy ,medicine.disease ,ω3 polyunsaturated fatty acids ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,business ,lcsh:RC581-607 ,Adjuvant ,medicine.drug ,Polyunsaturated fatty acid - Abstract
Diet composition may affect the onset and progression of chronic degenerative diseases, including cancer, whose pathogenesis relies on inflammatory processes. Growing evidence indicates that diet and its components critically contribute to human health, affecting the immune system, secretion of adipokines, and metabolic pathways. Colorectal cancer (CRC) is one of the leading causes of death worldwide. Antineoplastic drugs are widely used for CRC treatment, but drug resistance and/or off-target toxicity limit their efficacy. Dietary ω3 polyunsaturated fatty acids (PUFA) have been gaining great interest in recent years as possible anti-inflammatory and anticancer agents, especially in areas such as the large bowel, where the pro-inflammatory context promotes virtually all steps of colon carcinogenesis. Growing epidemiological, experimental, and clinical evidence suggests that ω3 PUFA may play a role in several stages of CRC management exhibiting antineoplastic activity against human CRC cells, improving the efficacy of radiation and chemotherapy, ameliorating cancer-associated secondary complications, and preventing CRC recurrence. These effects are most likely related to the immunomodulatory activities of ω3 PUFA that are able to influence several aspects of the inflammatory process ranging from inflammasome activation, leukocyte recruitment, production of immune mediators to differentiation, and activation of immune cells. In this review, we will focus on the potential use of ω3 PUFA as adjuvant agents together with chemo/radiotherapy, highlighting the immunomodulatory effects most likely responsible for their beneficial effects in different stages of CRC management.
- Published
- 2016
49. 3D (Three-Dimensional) Caco-2 Spheroids: Optimized in vitro Protocols to Favor Their Differentiation Process and to Analyze Their Cell Growth Behavior
- Author
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Alessandra Boe, Gabriella Rainaldi, and Sandra Gessani
- Subjects
Chemistry ,Caco-2 ,Cell growth ,Scientific method ,Spheroid ,Biophysics ,In vitro - Published
- 2016
50. Gender-related differences in lifestyle may affect health status
- Author
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Rosaria, Varì, Beatrice, Scazzocchio, Antonio, D'Amore, Claudio, Giovannini, Sandra, Gessani, and Roberta, Masella
- Subjects
Male ,Sex Characteristics ,Sex Factors ,Health Status ,Gender Identity ,Humans ,Female ,Obesity ,Lipid Metabolism ,Life Style - Abstract
Consistent epidemiological and clinical evidence strongly indicates that chronic non-communicable diseases are largely associated with four lifestyle risk factors: inadequate diet, physical inactivity, tobacco use, and excessive alcohol use. Notably, obesity, a worldwide-growing pathological condition determined by the combination between inadequate diet and insufficient physical activity, is now considered a main risk factor for most chronic diseases. Dietary habits and physical activity are strongly influenced by gender attitudes and behaviors that promote different patterns of healthy or unhealthy lifestyles among women and men. Furthermore, different roles and unequal relations between genders strongly interact with differences in social and economic aspects as well as cultural and societal environment. Because of the complex network of factors involved in determining the risk for chronic diseases, it has been promoting a systemic approach that, by integrating sex and gender analysis, explores how sex-specific biological factors and gender-related social factors can interact to influence the health status.
- Published
- 2016
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