43 results on '"Giuseppina Bologna"'
Search Results
2. Extracellular vesicles number and cell subtype may be influenced by diabetes mellitus and metformin in patients at high cardiovascular risk
- Author
-
Paola G. Simeone, Rossella Liani, Giuseppina Bologna, Romina Tripaldi, Augusto Di Castelnuovo, Pasquale Simeone, Damiano D'Ardes, Sebastiano Miscia, Francesco Cipollone, Marco Marchisio, Agostino Consoli, Paola Lanuti, and Francesca Santilli
- Subjects
Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Cardiology and Cardiovascular Medicine - Published
- 2023
3. Tear proteomics reveals the molecular basis of the efficacy of human recombinant nerve growth factor treatment for Neurotrophic Keratopathy
- Author
-
Damiana Pieragostino, Manuela Lanzini, Ilaria Cicalini, Maria Concetta Cufaro, Verena Damiani, Leonardo Mastropasqua, Vincenzo De Laurenzi, Mario Nubile, Paola Lanuti, Giuseppina Bologna, Luca Agnifili, and Piero Del Boccio
- Subjects
Male ,Proteomics ,Multidisciplinary ,Microscopy, Confocal ,Proteome ,Administration, Topical ,Science ,Recombinant Proteins ,Article ,Corneal Diseases ,Extracellular Vesicles ,Prognostic markers ,Rare Diseases ,Tears ,Nerve Growth Factor ,Humans ,Medicine ,Female ,Prospective Studies - Abstract
Neurotrophic Keratopathy (NK), classified as an orphan disease (ORPHA137596), is a rare degenerative corneal disease characterized by epithelial instability and decreased corneal sensitivity caused by the damage to the corneal nerves. The administration of human recombinant nerve growth factor (rhNGF) eye drops, as a licensed-in-Europe specific medication for treatment of moderate and severe NK, has added promising perspectives to the management of this disorder by providing a valid alternative to the neurotization surgery. However, few studies have been conducted to the molecular mechanism underlying the response to the treatment. Here, we carried out tears proteomics to highlight the protein expression during pharmacological treatment of NK (Data are available via ProteomeXchange with identifier PXD025408).Our data emphasized a proteome modulation during rhNGF treatment related to an increase in DNA synthesis, an activation of both BDNF signal and IL6 receptor. Furthermore, the amount of neuronal Extracellular Vesicles EVs (CD171+) correlated with the EVs carrying IL6R (CD126+) together associated to the inflammatory EVs (CD45+) in tears. Such scenario determined drug response, confirmed by an in vivo confocal microscopy analysis, showing an increase in length, density and number of nerve fiber branches during treatment. In summary, rhNGF treatment seems to determine an inflammatory micro-environment, mediated by functionalized EVs, defining the drug response by stimulating protein synthesis and fiber regeneration.
- Published
- 2022
4. Circulating Extracellular Vesicles Are Increased in Newly Diagnosed Celiac Disease Patients
- Author
-
Konstantinos Efthymakis, Giuseppina Bologna, Pasquale Simeone, Laura Pierdomenico, Giulia Catitti, Simone Vespa, Angelo Milano, Domenico De Bellis, Francesco Laterza, Assunta Pandolfi, Caterina Pipino, Michele Sallese, Marco Marchisio, Sebastiano Miscia, Matteo Neri, and Paola Lanuti
- Subjects
extracellular vesicles ,flow cytometry ,celiac disease ,gluten-free diet regimen (GFD) ,Nutrition and Dietetics ,Food Science - Abstract
Extracellular vesicles (EVs) are a class of circulating entities that are involved in intercellular crosstalk mechanisms, participating in homeostasis maintenance, and diseases. Celiac disease is a gluten-triggered immune-mediated disorder, characterized by the inflammatory insult of the enteric mucosa following local lymphocytic infiltration, resulting in villous atrophy. The goal of this research was the assessment and characterization of circulating EVs in celiac disease patients, as well as in patients already on an adequate gluten-free regimen (GFD). For this purpose, a novel and validated technique based on polychromatic flow cytometry that allowed the identification and enumeration of different EV sub-phenotypes was applied. The analysis evidenced that the total, annexin V+, leukocyte (CD45+), and platelet (CD41a+) EV counts were significantly higher in both newly diagnosed celiac disease patients and patients under GFD compared with the healthy controls. Endothelial-derived (CD31+) and epithelial-derived (EpCAM+) EV counts were significantly lower in subjects under gluten exclusion than in celiac disease patients, although EpCAM+ EVs maintained higher counts than healthy subjects. The numbers of EpCAM+ EVs were a statistically significant predictor of intraepithelial leukocytes (IEL). These data demonstrate that EVs could represent novel and potentially powerful disease-specific biomarkers in the context of celiac disease.
- Published
- 2022
5. Circulating extracellular vesicles as new inflammation marker in HIV infection
- Author
-
Luca Federici, Sebastiano Miscia, Antonio Auricchio, Michela Pontolillo, Damiana Pieragostino, Claudio Ucciferri, Piero Del Boccio, Marco Marchisio, Jacopo Vecchiet, Paola Lanuti, Maria Concetta Cufaro, Katia Falasca, and Giuseppina Bologna
- Subjects
Blood Platelets ,Proteomics ,0301 basic medicine ,CD31 ,Immunology ,Cell ,HIV Infections ,Inflammation ,Biology ,Flow cytometry ,Extracellular Vesicles ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Immunodeficiency ,medicine.diagnostic_test ,medicine.disease ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Viral replication ,medicine.symptom ,Intracellular - Abstract
Extracellular vesicles, released by cell pullulation, are surrounded by a phospholipid bilayer and carry proteins as well and genetic material. It has been shown that extracellular vesicles mediate intercellular communication in several conditions, such as inflammation, immunodeficiency, tumor growth, and viral infections. Here, we analyzed circulating levels of extracellular vesicles in order to clarify their role in chronic inflammation mechanisms characterizing HIV patients.We analyzed and subtyped circulating levels of extracellular vesicles, through a recently developed flow cytometry method. In detail, endothelial-derived extracellular vesicles (CD31+/CD41a-/CD45-, EMVs), extracellular vesicles stemming from leukocytes (CD45+, LMVs) and platelets (CD41a+/CD31+) were identified and enumerated. Moreover, we analyzed the extracellular vesicle protein cargo with proteomic analysis.Circulating levels of total extracellular vesicles, EMVs and LMVs were significantly lower in the HIV+ patients than in healthy subjects, whereas platelet-derived extracellular vesicles resulted higher in patients than in the healthy population. Proteomic analysis showed the upregulation of gammaIFN and IL1α, and down-regulation of OSM, NF-kB, LIF, and RXRA signaling resulted activated in this patients.These data demonstrate, for the first time that HIV infection induces the production of extracellular vesicles containing mediators that possibly feed the chronic inflammation and the viral replication. These two effects are connected as the inflammation itself induces the viral replication. We, therefore, hypothesize that HIV infection inhibits the production of extracellular vesicles that carry anti-inflammatory molecules.
- Published
- 2020
6. Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line
- Author
-
Francesco Avolio, Stefano Martinotti, Vladimir Kh. Khavinson, Jessica Elisabetta Esposito, Giulia Giambuzzi, Antonio Marino, Ekaterina Mironova, Riccardo Pulcini, Iole Robuffo, Giuseppina Bologna, Pasquale Simeone, Paola Lanuti, Simone Guarnieri, Svetlana Trofimova, Antonio Domenico Procopio, and Elena Toniato
- Subjects
Lipopolysaccharides ,THP-1 Cells ,Tumor Necrosis Factor-alpha ,Macrophages ,Organic Chemistry ,Endothelial Cells ,Dipeptides ,General Medicine ,Monocytes ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,peptides ,LPS ,monocytes ,cytokines ,STATs ,Cytokines ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
This study evaluates the effects of five different peptides, the Epitalon® tetrapeptide, the Vilon® dipeptide, the Thymogen® dipeptide, the Thymalin® peptide complex, and the Chonluten® tripeptide, as regulators of inflammatory and proliferative processes in the human monocytic THP-1, which is a human leukemia monocytic cell line capable of differentiating into macrophages by PMA in vitro. These peptides (Khavinson Peptides®), characterized by Prof. Khavinson from 1973 onwards, were initially isolated from animal tissues and found to be organ specific. We tested the capacity of the five peptides to influence cell cultures in vitro by incubating THP-1 cells with peptides at certain concentrations known for being effective on recipient cells in culture. We found that all five peptides can modulate key proliferative patterns, increasing tyrosine phosphorylation of mitogen-activated cytoplasmic kinases. In addition, the Chonluten tripeptide, derived from bronchial epithelial cells, inhibited in vitro tumor necrosis factor (TNF) production of monocytes exposed to pro-inflammatory bacterial lipopolysaccharide (LPS). The low TNF release by monocytes is linked to a documented mechanism of TNF tolerance, promoting attenuation of inflammatory action. Therefore, all peptides inhibited the expression of TNF and pro-inflammatory IL-6 cytokine stimulated by LPS on terminally differentiated THP-1 cells. Lastly, by incubating the THP1 cells, treated with the peptides, on a layer of activated endothelial cells (HUVECs activated by LPS), we observed a reduction in cell adhesion, a typical pro-inflammatory mechanism. Overall, the results suggest that the Khavinson Peptides® cooperate as natural inducers of TNF tolerance in monocyte, and act on macrophages as anti-inflammatory molecules during inflammatory and microbial-mediated activity.
- Published
- 2022
- Full Text
- View/download PDF
7. Extracellular Vesicles in pregnancy: Their potential role as a liquid biopsy
- Author
-
Danilo Buca, Francesco D’Antonio, Davide Buca, Francesca Di Sebastiano, Pasquale Simeone, Raffaella Di Girolamo, Giuseppina Bologna, Simone Vespa, Giulia Catitti, Marco Liberati, Sebastiano Miscia, and Paola Lanuti
- Subjects
Blood Platelets ,Extracellular Vesicles ,Reproductive Medicine ,Pregnancy ,Case-Control Studies ,Immunology ,Infant, Newborn ,Liquid Biopsy ,Obstetrics and Gynecology ,Immunology and Allergy ,Humans ,Premature Birth ,Female - Abstract
Extracellular Vesicles (EVs) are cell-derived particles released during different pathophysiological processes, circulating in many body fluids and mediating the inter-cellular crosstalk. We have analyzed, for the first time, different EV phenotypes and concentrations in the peripheral blood of uncomplicated pregnant women.In this prospective case-control study, uncomplicated singleton pregnant women at term (N = 59) and aged matched non-pregnant women (N = 21) were enrolled. Freshly drowned peripheral blood samples were stained for flow cytometry analyses of EVs.EVs derived from platelets, leukocytes, endothelial and epithelial cells were identified and counted. Platelet-derived EVs were higher in pregnant compared to non-pregnant women, both in terms of absolute counts (2064.4 ± 1156.3 vs 701.1 ± 378.8; p 0.0001) and percentages (27.6 ± 17.2 vs 10.7 ± 5.9; p 0.0001). The opposite pattern was observed both for concentrations of endothelial-EV counts (525.8 ± 499.6 vs 844.7 ± 652.9; p = 0.007) and percentages (6.1 ± 5.5 vs 11.8 ± 8.0; p 0.0001) and leukocyte-derived EV percentages (10.2 ± 7.4 vs 17.9 ± 11.2; p = 0.002) EVs.Uncomplicated pregnancies are characterized by a specific EV signature. These cell-derived particles may therefore represent promising biomarkers of different pathological conditions complicating pregnancies, such as preeclampsia or preterm birth.
- Published
- 2022
8. Integrative proteomic and functional analyses provide novel insights into the action of the repurposed drug candidate nitroxoline in AsPC-1 cells
- Author
-
Alessandro Cama, Maria Cristina Di Bella, Giuseppina Bologna, Valeria Bertagnolo, Luca Scotti, Serena Veschi, Rosalba Florio, Laura De Lellis, Paola Lanuti, Erminia Carletti, Marco Marchisio, Maurizio Ronci, and Federica Brugnoli
- Subjects
Proteomics ,Cell biology ,DNA damage ,lcsh:Medicine ,Apoptosis ,Article ,NO ,Cell Line ,chemistry.chemical_compound ,Downregulation and upregulation ,Cell Line, Tumor ,Humans ,Shotgun proteomics ,lcsh:Science ,Cell Proliferation ,Regulation of gene expression ,Neoplastic ,Tumor ,Multidisciplinary ,poptosis ,Chemistry ,Cell Cycle ,lcsh:R ,Nitroquinolines ,Pancreatic cancer ,In vitro ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,Gene Expression Regulation ,Nitroxoline ,Cell culture ,Cancer research ,lcsh:Q ,DNA Damage - Abstract
We recently identified nitroxoline as a repurposed drug candidate in pancreatic cancer (PC) showing a dose-dependent antiproliferative activity in different PC cell lines. This antibiotic is effective in several in vitro and animal cancer models. To date, the mechanisms of nitroxoline anticancer action are largely unknown. Using shotgun proteomics we identified 363 proteins affected by nitroxoline treatment in AsPC-1 pancreatic cancer cells, including 81 consistently deregulated at both 24- and 48-hour treatment. These proteins previously unknown to be affected by nitroxoline were mostly downregulated and interconnected in a single highly-enriched network of protein-protein interactions. Integrative proteomic and functional analyses revealed nitroxoline-induced downregulation of Na/K-ATPase pump and β-catenin, which associated with drastic impairment in cell growth, migration, invasion, increased ROS production and induction of DNA damage response. Remarkably, nitroxoline induced a previously unknown deregulation of molecules with a critical role in cell bioenergetics, which resulted in mitochondrial depolarization. Our study also suggests that deregulation of cytosolic iron homeostasis and of co-translational targeting to membrane contribute to nitroxoline anticancer action. This study broadens our understanding of the mechanisms of nitroxoline action, showing that the drug modulates multiple proteins crucial in cancer biology and previously unknown to be affected by nitroxoline.
- Published
- 2020
9. Chondrogenic Differentiation of Human Wharton’s Jelly and Bone Marrow-Derived Mesenchymal Stem Cells: Focus on the Role of an Acrylamide-Free Cross-Linked Hyaluronic Acid Hydrogel
- Author
-
Letizia Pelusi, Valeria Schiavone, Giuseppina Bologna, Pietro Cerritelli, Deborah Lezza, Andrea Pantalone, Manuela Santalucia, Roberto Buda, Assunta Pandolfi, and Domitilla Mandatori
- Published
- 2021
10. Diagnostic Impact of Radiological Findings and Extracellular Vesicles: Are We Close to Radiovesicolomics?
- Author
-
Francesco Lorenzo Serafini, Paola Lanuti, Andrea Delli Pizzi, Luca Procaccini, Michela Villani, Alessio Lino Taraschi, Luca Pascucci, Erica Mincuzzi, Jacopo Izzi, Piero Chiacchiaretta, Davide Buca, Giulia Catitti, Giuseppina Bologna, Pasquale Simeone, Damiana Pieragostino, and Massimo Caulo
- Subjects
General Immunology and Microbiology ,radiomics ,QH301-705.5 ,radiovesicolomics ,Review ,Biology (General) ,General Agricultural and Biological Sciences ,extracellular vesicles ,artificial intelligence ,General Biochemistry, Genetics and Molecular Biology ,radiology - Abstract
Simple Summary Over the years, diagnostic tests such as in radiology and flow cytometry have become more and more powerful in the constant struggle against different pathologies, some of which are life-threatening. The possibility of using these “weapons” in a conjugated manner could result in higher healing and prevention rates, and a decrease in late diagnosis diseases. Different correlations among pathologies, extracellular vesicles (EVs), and radiological findings were recently demonstrated by many authors. Together with the increasing importance of “omics” sciences, and artificial intelligence in this new century, the perspective of a new research field called “radiovesicolomics” could be the missing link, enabling a different approach to disease diagnosis and treatment. Abstract Currently, several pathologies have corresponding and specific diagnostic and therapeutic branches of interest focused on early and correct detection, as well as the best therapeutic approach. Radiology never ceases to develop newer technologies in order to give patients a clear, safe, early, and precise diagnosis; furthermore, in the last few years diagnostic imaging panoramas have been extended to the field of artificial intelligence (AI) and machine learning. On the other hand, clinical and laboratory tests, like flow cytometry and the techniques found in the “omics” sciences, aim to detect microscopic elements, like extracellular vesicles, with the highest specificity and sensibility for disease detection. If these scientific branches started to cooperate, playing a conjugated role in pathology diagnosis, what could be the results? Our review seeks to give a quick overview of recent state of the art research which investigates correlations between extracellular vesicles and the known radiological features useful for diagnosis.
- Published
- 2021
11. Oxidative Distress Induces Wnt/β-Catenin Pathway Modulation in Colorectal Cancer Cells: Perspectives on APC Retained Functions
- Author
-
Federico Selvaggi, Maria Carmela Di Marcantonio, Gitana Aceto, Carmelo Moscatello, Maria Cristina Curia, Rossano Lattanzio, Alessio Ferrone, Roberto Cotellese, Teresa Catalano, Emira D’Amico, Paola Lanuti, and Giuseppina Bologna
- Subjects
Cancer Research ,Colorectal cancer ,Wnt/β-Catenin ,colorectal cancer ,Oxidative phosphorylation ,Biology ,medicine.disease_cause ,Article ,APC, Wnt/β-Catenin, colorectal cancer, gene expression, microenvironment, oxidative stress, protein expression ,Gene expression ,medicine ,oxidative stress ,protein expression ,RC254-282 ,Wnt signaling pathway ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,microenvironment ,Phenotype ,digestive system diseases ,APC ,Oncology ,Cytoplasm ,Catenin ,Cancer research ,gene expression ,Oxidative stress - Abstract
Simple Summary The dysregulation of Wnt pathways is involved in colorectal carcinogenesis. H2O2 differentially regulates the Wnt/β-Catenin pathway in colorectal cancer (CRC), but the molecular mechanisms remain unclear. Cellular stress might also stimulate APC protein production retaining some functions in N-terminus and lead to cancer progression. The effect of oxidative distress on Wnt/β-catenin signaling in the light of APC functions is unknown. We exposed starved HCT116, SW480 and SW620 CRC cell lines to H2O2-induced short-term oxidative stress. This treatment promoted the activation of β-Catenin and increased cytoplasmic APC. H2O2 regulated gene expression, related to cellular phenotype and stimulated both Wnt/β-Catenin-dependent and -independent signaling. These findings suggest that oxidative distress may influence APC functions in Wnt signaling and open up new perspectives to develop personalized therapeutic approaches for CRC. Abstract Colorectal cancer (CRC) is a multistep process that arises in the colic tissue microenvironment. Oxidative stress plays a role in mediating CRC cell survival and progression, as well as promoting resistance to therapies. CRC progression is associated with Wnt/β-Catenin signaling dysregulation and loss of proper APC functions. Cancer recurrence/relapse has been attributed to altered ROS levels, produced in a cancerous microenvironment. The effect of oxidative distress on Wnt/β-Catenin signaling in the light of APC functions is unclear. This study evaluated the effect of H2O2-induced short-term oxidative stress in HCT116, SW480 and SW620 cells with different phenotypes of APC and β-Catenin. The modulation and relationship of APC with characteristic molecules of Wnt/β-Catenin were assessed in gene and protein expression. Results indicated that CRC cells, even when deprived of growth factors, under acute oxidative distress conditions by H2O2 promote β-Catenin expression and modulate cytoplasmic APC protein. Furthermore, H2O2 induces differential gene expression depending on the cellular phenotype and leading to favor both Wnt/Catenin-dependent and -independent signaling. The exact mechanism by which oxidative distress can affect Wnt signaling functions will require further investigation to reveal new scenarios for the development of therapeutic approaches for CRC, in the light of the conserved functions of APC.
- Published
- 2021
- Full Text
- View/download PDF
12. BNT162b2 mRNA Vaccination Leads to Long-Term Protection from COVID-19 Disease
- Author
-
Katia Falasca, Giuseppina Bologna, Luca Natale, Domenico De Bellis, Mirco Zucchelli, Laura Pierdomenico, Giulia Catitti, Ines Bucci, Pasquale Simeone, Damiana Pieragostino, Vincenzo De Laurenzi, Bruna Sinjari, Liborio Stuppia, Simone Vespa, Ilaria Cicalini, Jacopo Vecchiet, Claudia Rossi, Piero Del Boccio, and Paola Lanuti
- Subjects
Cellular immunity ,Immunology ,Disease ,Persistence (computer science) ,Memory cell ,Drug Discovery ,Medicine ,Pharmacology (medical) ,Adverse effect ,Pharmacology ,biology ,business.industry ,SARS-CoV-2 ,Communication ,vaccines ,spike-specific T-cells ,anti-S1 IgG ,Vaccination ,Infectious Diseases ,biology.protein ,BNT162b2 ,Antibody ,business ,CD8 - Abstract
The efficacy of SARS-CoV-2 mRNA-based vaccines in preventing COVID-19 disease has been extensively demonstrated; however, it is of uttermost importance to acquire knowledge on the persistence of immune-protection both in terms of levels of neutralizing antibodies and specialized memory cells. This can provide important scientific basis for decisions on the need of additional vaccine doses and on when these should be administered thus resulting in an improvement in vaccination schedules. Here, we briefly report the changes in antibody levels and cellular immunity following BNT162b2 administration. We show an important fall in anti S1-Spike antibodies in BNT162b2 vaccinated subjects overtime, paralleled by a contextual consolidation of specific spike (S) T-cells, mainly of the CD8+ compartment. Contrariwise, CD4+ S-specific response shows a considerable interindividual variability. These data suggest that the well-known antibody drop in vaccinated subjects is replaced by memory cell consolidation that can protect from severe adverse effects of SARS-CoV-2 infection.
- Published
- 2021
13. Picture of the Favourable Immune Profile Induced by Anti-SARS-CoV-2 Vaccination
- Author
-
Annalina Sarra, Liborio Stuppia, Federica Di Marco, Sara Verrocchio, Tonio Di Battista, Adelia Evangelista, Mirco Zucchelli, Claudia Rossi, Paola Lanuti, Simone Stefanetti, Verena Damiani, Pasquale Simeone, Daniela Semeraro, Laura Pierdomenico, Piero Del Boccio, Giulia Catitti, Simone Vespa, Ines Bucci, Giuseppina Bologna, Vincenzo De Laurenzi, Bruna Sinjari, Ilaria Cicalini, and Damiana Pieragostino
- Subjects
Coronavirus disease 2019 (COVID-19) ,business.industry ,SARS-CoV-2 ,QH301-705.5 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Medicine (miscellaneous) ,vaccines ,spike-specific T-cells ,General Biochemistry, Genetics and Molecular Biology ,Article ,anti-S1 IgG ,Dried blood spot ,Vaccination ,Immune system ,Immunology ,Cohort ,Pandemic ,Medicine ,Biology (General) ,business ,Adverse effect - Abstract
COVID-19 pandemic has hit people’s health, economy, and society worldwide. Great confidence in returning to normality has been placed in the vaccination campaign. The knowledge of individual immune profiles and the time required to achieve immunological protection is crucial to choose the best vaccination strategy. We compared anti-S1 antibody levels produced over time by BNT162b2 and AZD1222 vaccines and evaluated the induction of antigen-specific T-cells. A total of 2569 anti-SARS-CoV-2 IgG determination on dried blood spot samples were carried out, firstly in a cohort of 1181 individuals at random time-points, and subsequently, in an independent cohort of 88 vaccinated subjects, up to the seventeenth week from the first dose administration. Spike-specific T-cells were analysed in seronegative subjects between the two doses. AZD1222 induced lower anti-S1 IgG levels as compared to BNT162b2. Moreover, 40% of AZD1222 vaccinated subjects and 3% of BNT162b2 individuals resulted in seronegative during all the time-points, between the two doses. All these subjects developed antigen-specific T cells, already after the first dose. These results suggest that this test represents an excellent tool for a wide sero-surveillance. Both vaccines induce a favourable immune profile guaranteeing efficacy against severe adverse effects of SARS-CoV-2 infection, already after the first dose administration.
- Published
- 2021
14. Endogenous PCSK9 may influence circulating CD45neg/CD34bright and CD45neg/CD34bright/CD146neg cells in patients with type 2 diabetes mellitus
- Author
-
Marco Marchisio, Sonia Ciotti, Romina Tripaldi, Rossella Liani, Francesca Santilli, Francesco Cipollone, Pasquale Simeone, Augusto Di Castelnuovo, Paola Simeone, Paola Lanuti, and Giuseppina Bologna
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Molecular biology ,Science ,Antigens, CD34 ,Endogeny ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,Endocrinology ,0302 clinical medicine ,In vivo ,Internal medicine ,medicine ,Humans ,In patient ,Progenitor cell ,Aged ,Endothelial Progenitor Cells ,Multidisciplinary ,business.industry ,PCSK9 ,Biological techniques ,Endocrine system and metabolic diseases ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,Middle Aged ,Proprotein convertase ,Cross-Sectional Studies ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Leukocyte Common Antigens ,Medicine ,Kexin ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Proprotein Convertase 9 ,business ,Biomarkers - Abstract
Protease proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of LDL cholesterol clearance and has been associated with cardiovascular risk. PCSK9 inhibitors increase in vivo circulating endothelial progenitor cells (EPCs), a subtype of immature cells involved in ongoing endothelial repair. We hypothesized that the effect of PCSK9 on vascular homeostasis may be mediated by EPCs in patients with or without type 2 diabetes mellitus (T2DM). Eighty-two patients (45 with, 37 without T2DM) at high cardiovascular risk were enrolled in this observational study. Statin treatment was associated with higher circulating levels of PCSK9 in patients with and without T2DM (p neg/CD34bright (total EPC compartment) (p = 0.016) and CD45neg/CD34bright/CD146neg (early EPC) (p = 0.040) only among patients with T2DM. In the whole group of patients, statin treatment was the only independent predictor of low number of CD45neg/CD34bright (β = − 0.230; p = 0.038, adjusted R2 = 0.041). Among T2DM patients, PCSK9 circulating levels were inversely related and predicted both the number of CD45neg/CD34bright (β = − 0.438; p = 0.003, adjusted R2 = 0.173), and CD45neg/CD34bright/CD146neg (β = − 0.458; p = 0.002, adjusted R2 = 0.191) independently of age, gender, BMI and statin treatment. In high-risk T2DM patients, high endogenous levels of PCSK9 may have a detrimental effect on EPCs by reducing the endothelial repair and worsening the progression of atherothrombosis.
- Published
- 2021
15. The Characterization of Regulatory T-Cell Profiles in Alzheimer’s Disease and Multiple Sclerosis
- Author
-
Fabio Buttari, Fausta Ciccocioppo, Sebastiano Miscia, Giuseppina Bologna, Eva Ercolino, Roberta Fantozzi, Marco Marchisio, Pasquale Simeone, Astrid Thomas, Paola Lanuti, Laura Pierdomenico, Marco Onofrj, and Diego Centonze
- Subjects
Adult ,Male ,0301 basic medicine ,Multiple Sclerosis ,Regulatory T cell ,Neuroimmunology ,Population ,lcsh:Medicine ,chemical and pharmacologic phenomena ,Disease ,Settore MED/26 ,T-Lymphocytes, Regulatory ,Article ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Alzheimer Disease ,Antigens, CD ,T-Lymphocyte Subsets ,medicine ,Humans ,education ,lcsh:Science ,Aged ,education.field_of_study ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,Multiple sclerosis ,Apyrase ,lcsh:R ,Peripheral tolerance ,hemic and immune systems ,HLA-DR Antigens ,Middle Aged ,medicine.disease ,Acquired immune system ,Cellular neuroscience ,Up-Regulation ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Female ,lcsh:Q ,business ,030217 neurology & neurosurgery - Abstract
Regulatory T Cells (Tregs) are a T-lymphocyte subset involved in the maintenance of immune peripheral tolerance. Despite evidence of the adaptive immune system’s role in Alzheimer’s Disease (AD), the involvement of Tregs is still not clear. We focused on the Flow-Cytometry analysis of the Treg frequencies and phenotypes in the AD. The aim of the study is to analyse similarities and differences in Tregs profile between Alzheimer’s Disease and Multiple Sclerosis. Regulatory T Cells (CD4+/CD25high/CD127low-neg) were identified using an innovative Flow Cytometry method and subtyped as Resting (analysed CD45RApos/CD25dim), Activated (CD45RAneg/CD25bright) and Secreting (CD45RAneg/CD25dim) cells. Our data demonstrate a significant decrease in the total and Resting Tregs in AD patients when compared to healthy subjects. The percentage of the results of the Resting Tregs were also reduced in MS patients together with a parallel frequency increase of Activated Tregs. Our data suggest that altered Treg phenotypes observed in both diseases could play a role in the impairment of the Treg-mediated immunological tolerance, recalling a possible link between the two pathologies. Given that this study was conducted on a restricted population, if confirmed by a further and enlarged study, the implications of the autoimmune mechanisms in AD pathophysiology could open new immunotherapeutic perspectives based on Treg modulation.
- Published
- 2019
16. Phenotypic and Proteomic Analysis Identifies Hallmarks of Blood Circulating Extracellular Vesicles in NSCLC Responders to Immune Checkpoint Inhibitors
- Author
-
Luca Federici, Sebastiano Miscia, Nicola Tinari, Damiana Pieragostino, Pietro Di Marino, Luciana Irtelli, Rosalba Florio, Marco Marchisio, Antonino Grassadonia, Pasquale Simeone, Laura De Lellis, Paola Lanuti, Michele De Tursi, Maria Concetta Cufaro, Piero Del Boccio, Alessandro Cama, Serena Veschi, Giuseppina Bologna, and Davide Brocco
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,lcsh:RC254-282 ,Article ,Flow cytometry ,immune checkpoint inhibitors ,03 medical and health sciences ,0302 clinical medicine ,Cancer immunotherapy ,medicine ,Shotgun proteomics ,non-small cell lung cancer ,Chemotherapy ,cancer immunotherapy ,medicine.diagnostic_test ,business.industry ,Immunotherapy ,Extracellular vesicle ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Proteome ,Cancer research ,Biomarker (medicine) ,biomarker ,business ,extracellular vesicles - Abstract
Simple Summary Purpose of this study was to investigate the prognostic and predictive role of blood circulating extracellular vesicles (EVs) in patients with advanced non-small cell lung cancer treated with immunotherapy. A newly optimized flow cytometry protocol was applied for identification and subtyping of blood circulating EVs in a total cohort of 59 NSCLC patients, which included 31 patients treated with anti-PD-1/PD-L1 agents and 28 patients treated with traditional chemotherapy. Our results show that pre-treatment concentration of blood circulating endothelial-derived EVs was correlated with overall survival and clinical response in patients treated with immunotherapy. Additionally, proteomic analysis of purified blood circulating EVs indicated differences in EV protein cargo between responders and non-responders to immunotherapy. These findings may pave the way to the identification of novel immunotherapy biomarkers in patients with advanced NSCLC. Abstract Immune checkpoint inhibitors (ICIs) induce durable clinical responses only in a subset of advanced non-small cell lung cancer (NSCLC) patients. There is a need to identify mechanisms of ICI resistance and immunotherapy biomarkers to improve clinical benefit. In this study, we evaluated the prognostic and predictive value of circulating endothelial and leukocyte-derived extracellular vesicles (EV) in patients with advanced NSCLC treated with anti-PD-1/PD-L1 agents. In addition, the relationship between total blood circulating EV proteome and response to ICIs was investigated. An optimized flow cytometry method was employed for the identification and subtyping of blood circulating EVs in 59 patients with advanced NSCLC. Blood samples were collected from patients receiving anti-PD-1/PD-L1 inhibitors (n = 31) or chemotherapy (n = 28). An exploratory proteomic analysis of sorted blood EVs was conducted in a subset of patients. Our results show that a low blood concentration of circulating endothelial-derived EVs before treatment was strongly associated to longer overall survival (p = 0.0004) and higher disease control rate (p = 0.045) in patients treated with ICIs. Interestingly, shotgun proteomics revealed that EVs of responders to anti-PD-1 therapy had a specific protein cargo before treatment. In addition, EV protein cargo was specifically modulated during immunotherapy. We identified a previously unknown association between circulating endothelial-derived extracellular vesicle concentration and immunotherapy-related clinical outcomes. We also observed differences in circulating extracellular vesicle proteome according to anti-PD-1-based treatment response in NSCLC patients. Overall, these results may contribute to the identification of novel circulating biomarkers for rational immunotherapy approaches in patients affected by NSCLC.
- Published
- 2021
17. Flow Cytometry Analysis of Circulating Extracellular Vesicle Subtypes from Fresh Peripheral Blood Samples
- Author
-
Sebastiano Miscia, Damiana Pieragostino, Pasquale Simeone, Domenico Bosco, Eva Ercolino, Piero Del Boccio, Marco Marchisio, Francesca Antonini, Giuseppina Bologna, Christian Celia, Laura Pierdomenico, Luisa Di Marzio, Daniele Vergara, Genny Del Zotto, Antonella Fontana, Paola Lanuti, Alessia Ventrella, Marchisio, M., Simeone, P., Bologna, G., Ercolino, E., Pierdomenico, L., Pieragostino, D., Ventrella, A., Antonini, F., Del Zotto, G., Vergara, D., Celia, C., Di Marzio, L., Del Boccio, P., Fontana, A., Bosco, D., Miscia, S., and Lanuti, P.
- Subjects
0301 basic medicine ,Proteomics ,Polychromatic flow cytometry ,polychromatic flow cytometry ,030204 cardiovascular system & hematology ,Extracellular vesicles ,Sensitivity and Specificity ,Catalysis ,Article ,Flow cytometry ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,Plasma ,0302 clinical medicine ,proteomics ,Basic research ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Particle Size ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,medicine.diagnostic_test ,Chemistry ,Organic Chemistry ,Liquid Biopsy ,Reproducibility of Results ,biomarkers ,General Medicine ,Extracellular vesicle ,Biomarker ,fresh peripheral blood ,Cell sorting ,Flow Cytometry ,Peripheral blood ,Computer Science Applications ,Cell biology ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Potential biomarkers ,Fresh peripheral blood ,extracellular vesicles - Abstract
Extracellular vesicles (EVs) are released by shedding during different physiological processes and are increasingly thought to be new potential biomarkers. However, the impact of pre-analytical processing phases on the final measurement is not predictable and for this reason, the translation of basic research into clinical practice has been precluded. Here we have optimized a simple procedure in combination with polychromatic flow cytometry (PFC), to identify, classify, enumerate, and separate circulating EVs from different cell origins. This protocol takes advantage of a lipophilic cationic dye (LCD) able to probe EVs. Moreover, the application of the newly optimized PFC protocol here described allowed the obtainment of repeatable EVs counts. The translation of this PFC protocol to fluorescence-activated cell sorting allowed us to separate EVs from fresh peripheral blood samples. Sorted EVs preparations resulted particularly suitable for proteomic analyses, which we applied to study their protein cargo. Here we show that LCD staining allowed PFC detection and sorting of EVs from fresh body fluids, avoiding pre-analytical steps of enrichment that could impact final results. Therefore, LCD staining is an essential step towards the assessment of EVs clinical significance.
- Published
- 2020
- Full Text
- View/download PDF
18. Extracellular Vesicles in Feto-Maternal Crosstalk and Pregnancy Disorders
- Author
-
Melania Febbo, Marco Liberati, Sara Cugini, Sebastiano Miscia, Pasquale Simeone, Ester Vitacolonna, Danilo Buca, Paola Lanuti, Davide Buca, Francesca Musca, Alice D'Amico, Giuseppina Bologna, Francesco D'Antonio, and Dolores D'Arcangelo
- Subjects
0301 basic medicine ,pre-eclampsia ,Placenta ,syncytiotrophoblast ,Disease ,Review ,Bioinformatics ,Extracellular vesicles ,Catalysis ,Preeclampsia ,Inorganic Chemistry ,lcsh:Chemistry ,fetal growth restriction ,03 medical and health sciences ,Extracellular Vesicles ,0302 clinical medicine ,Syncytiotrophoblast ,Pregnancy ,medicine ,Humans ,Physical and Theoretical Chemistry ,placental extracellular vesicles ,Molecular Biology ,Pathological ,lcsh:QH301-705.5 ,Maternal-Fetal Exchange ,Spectroscopy ,Fetal Growth Retardation ,business.industry ,Organic Chemistry ,General Medicine ,medicine.disease ,preterm-labor ,gestational diabetes mellitus ,Computer Science Applications ,Gestational diabetes ,Crosstalk (biology) ,Diabetes, Gestational ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,lcsh:QD1-999 ,030220 oncology & carcinogenesis ,Female ,business ,Biomarkers - Abstract
Extracellular vesicles (EVs) actively participate in inter-cellular crosstalk and have progressively emerged as key players of organized communities of cells within multicellular organisms in health and disease. For these reasons, EVs are attracting the attention of many investigators across different biomedical fields. In this scenario, the possibility to study specific placental-derived EVs in the maternal peripheral blood may open novel perspectives in the development of new early biomarkers for major obstetric pathological conditions. Here we reviewed the involvement of EVs in feto–maternal crosstalk mechanisms, both in physiological and pathological conditions (preeclampsia, fetal growth restriction, preterm labor, gestational diabetes mellitus), also underlining the usefulness of EV characterization in maternal–fetal medicine.
- Published
- 2020
19. Diameters and fluorescence calibration for extracellular vesicle analyses by flow cytometry
- Author
-
Luisa Stellin, Sebastiano Miscia, Francesca Diomede, Pasquale Simeone, Laura Pierdomenico, Vilberto Stocchi, Marco Marchisio, Rossella Grande, Michele Guescini, Lavinia Vittoria Lotti, Giuseppina Bologna, Stefano Papa, Christian Celia, Eva Ercolino, Barbara Canonico, Oriana Trubiani, Maria Teresa Guagnano, Felisa Cilurzo, Simone Vespa, and Paola Lanuti
- Subjects
0301 basic medicine ,Materials science ,Clinical settings ,030204 cardiovascular system & hematology ,Extracellular vesicles ,Article ,Catalysis ,Flow cytometry ,lcsh:Chemistry ,Inorganic Chemistry ,Rosetta bead system ,Extracellular Vesicles ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Cells, Cultured ,Spectroscopy ,standardization ,Reproducibility ,medicine.diagnostic_test ,Immunomagnetic Separation ,extracellular vesicles (EVs) ,flow cytometry ,Organic Chemistry ,Mesenchymal Stem Cells ,General Medicine ,Extracellular vesicle ,Fluorescence ,Dynamic Light Scattering ,Computer Science Applications ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Biomedical engineering - Abstract
Extracellular vesicles (EVs) play a crucial role in the intercellular crosstalk. Mesenchymal stem cell-derived EVs (MSC-EVs), displaying promising therapeutic roles, contribute to the strong rationale for developing EVs as an alternative therapeutic option. EV analysis still represents one of the major issues to be solved in order to translate the use of MSC-EV detection in clinical settings. Even if flow cytometry (FC) has been largely applied for EV studies, the lack of consensus on protocols for FC detection of EVs generated controversy. Standard FC procedures, based on scatter measurements, only allows the detection of the &ldquo, tip of the iceberg&rdquo, of all EVs. We applied an alternative FC approach based on the use of a trigger threshold on a fluorescence channel. The EV numbers obtained by the application of the fluorescence triggering resulted significantly higher in respect to them obtained from the same samples acquired by placing the threshold on the side scatter (SSC) channel. The analysis of EV concentrations carried out by three different standardized flow cytometers allowed us to achieve a high level of reproducibility (CV <, 20%). By applying the here-reported method highly reproducible results in terms of EV analysis and concentration measurements were obtained.
- Published
- 2020
20. Circulating Cancer Stem Cell-Derived Extracellular Vesicles as a Novel Biomarker for Clinical Outcome Evaluation
- Author
-
Laura Pierdomenico, Clara Natoli, Sebastiano Miscia, Nicola Tinari, Damiana Pieragostino, Paola Lanuti, Fausta Ciccocioppo, Davide Brocco, I. G. Rapposelli, Vincenzo Graziano, P. Del Boccio, Maria Concetta Cufaro, Eva Ercolino, Marta Peri, Giuseppina Bologna, Paola Simeone, Marco Marchisio, Antonino Grassadonia, M. De Tursi, P. Di Marino, Grassadonia, A [0000-0002-2459-0661], Del Boccio, P [0000-0003-1653-2194], Marchisio, M [0000-0003-3058-3422], Natoli, C [0000-0001-7295-0230], and Apollo - University of Cambridge Repository
- Subjects
Oncology ,CD31 ,medicine.medical_specialty ,Article Subject ,32 Biomedical and Clinical Sciences ,Proteomics ,lcsh:RC254-282 ,Flow cytometry ,Clinical Research ,Cancer stem cell ,Internal medicine ,medicine ,2.1 Biological and endogenous factors ,Cancer ,2 Aetiology ,medicine.diagnostic_test ,business.industry ,Prevention ,Cell sorting ,3211 Oncology and Carcinogenesis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Precision medicine ,medicine.disease ,4.1 Discovery and preclinical testing of markers and technologies ,Biomarker (medicine) ,4 Detection, screening and diagnosis ,business ,Research Article ,4.2 Evaluation of markers and technologies - Abstract
The recent introduction of the “precision medicine” concept in oncology pushed cancer research to focus on dynamic measurable biomarkers able to predict responses to novel anticancer therapies in order to improve clinical outcomes. Recently, the involvement of extracellular vesicles (EVs) in cancer pathophysiology has been described, and given their release from all cell types under specific stimuli, EVs have also been proposed as potential biomarkers in cancer. Among the techniques used to study EVs, flow cytometry has a high clinical potential. Here, we have applied a recently developed and simplified flow cytometry method for circulating EV enumeration, subtyping, and isolation from a large cohort of metastatic and locally advanced nonhaematological cancer patients (N = 106); samples from gender- and age-matched healthy volunteers were also analysed. A large spectrum of cancer-related markers was used to analyse differences in terms of peripheral blood circulating EV phenotypes between patients and healthy volunteers, as well as their correlation to clinical outcomes. Finally, EVs from patients and controls were isolated by fluorescence-activated cell sorting, and their protein cargoes were analysed by proteomics. Results demonstrated that EV counts were significantly higher in cancer patients than in healthy volunteers, as previously reported. More interestingly, results also demonstrated that cancer patients presented higher concentrations of circulating CD31+ endothelial-derived and tumour cancer stem cell-derived CD133 + CD326- EVs, when compared to healthy volunteers. Furthermore, higher levels of CD133 + CD326− EVs showed a significant correlation with a poor overall survival. Additionally, proteomics analysis of EV cargoes demonstrated disparities in terms of protein content and function between circulating EVs in cancer patients and healthy controls. Overall, our data strongly suggest that blood circulating cancer stem cell-derived EVs may have a role as a diagnostic and prognostic biomarker in cancer.
- Published
- 2019
21. Neurodegenerative diseases as proteinopathies-driven immune disorders
- Author
-
Piero Del Boccio, Laura Pierdomenico, Paola Lanuti, Sebastiano Miscia, Damiana Pieragostino, Marco Marchisio, Fausta Ciccocioppo, Eva Ercolino, Giuseppina Bologna, and Pasquale Simeone
- Subjects
0301 basic medicine ,medicine.medical_treatment ,adaptive immunity ,choroid plexus ,immunotherapy ,innate immunity ,neurodegenerative diseases ,neuroinflammation ,proteinopathies ,Inflammation ,Review ,lcsh:RC346-429 ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Developmental Neuroscience ,Medicine ,lcsh:Neurology. Diseases of the nervous system ,Neuroinflammation ,Innate immune system ,business.industry ,Neurodegeneration ,Immunotherapy ,medicine.disease ,Acquired immune system ,030104 developmental biology ,medicine.symptom ,business ,Neuroscience ,030217 neurology & neurosurgery ,Immune activation - Abstract
In the pathophysiology of neurodegenerative disorders, the role of misfolded protein deposition leading to neurodegeneration has been primarily discussed. In the last decade, however, it has been proposed a parallel involvement of innate immune activation, chronic inflammation and adaptive immunity in the neurodegeneration mechanisms triggered by proteinopathies. New insights in the neurodegenerative field strongly suggest a role for the immune system in the pathophysiology of neurodegenerative disorders. Therefore, the hypothesis underlining the modulation of the innate and the adaptive immune system in the events linked to brain deposition of misfolded proteins could open new perspectives in the setting of specific immunotherapeutic strategies for the treatment of neurodegenerative diseases. Therefore, we have reviewed the pathogenic hypothesis in neurodegenerative pathologies, underling the links between the deposition of misfolded protein mechanisms and the immune activation.
- Published
- 2019
22. Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib
- Author
-
Elisa Taschin, Francesca Schiavi, Renato Mariani-Costantini, Simone Vespa, Paola Lanuti, Giuseppina Bologna, Lorenzo Tramontana, Vinagolu K. Rajasekhar, Rosalba Florio, Simone Guarnieri, Marco Marchisio, Mario Sanna, Giuseppe Opocher, Diana L. Esposito, Rosa Visone, Artenca Sheu, Lavinia Vittoria Lotti, Cecilia Söderberg-Nauclér, Cosmo Rossi, Alessandro Cama, Mattia Russel Pantalone, Andrea D’Argenio, Annalisa Morgano, Silvia Perconti, Sampath Chandra Prasad, Carlo Terenzio Paties, Fabio Verginelli, and Angelo Veronese
- Subjects
0301 basic medicine ,Mesenchymal stem-like cells ,Mitochondria ,Neurogenesis ,Paraganglioma ,Vasculogenesis ,Xenograft ,2734 ,Neurology (clinical) ,Cellular and Molecular Neuroscience ,Organogenesis ,Primary Cell Culture ,Antineoplastic Agents ,PDGFRA ,Mice, SCID ,Biology ,Pathology and Forensic Medicine ,Cell Line ,03 medical and health sciences ,Neural Stem Cells ,Mice, Inbred NOD ,medicine ,Tumor Microenvironment ,Animals ,Humans ,Tumor microenvironment ,Original Paper ,Mesenchymal stem cell ,Correction ,medicine.disease ,Xenograft Model Antitumor Assays ,Neural stem cell ,Neuroepithelial cell ,MicroRNAs ,030104 developmental biology ,Imatinib mesylate ,Head and Neck Neoplasms ,Cancer research ,Imatinib Mesylate - Abstract
Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts. We comparatively investigated these unique complementary materials using morphofunctional, ultrastructural and flow cytometric assays accompanied by microRNA studies. We found that paragangliomas contain stem-like cells with hybrid mesenchymal/vasculoneural phenotype, stabilized and expanded in the derived cultures. The viability and growth of such cultures depended on the downregulation of the miR-200 and miR-34 families, which allowed high PDGFRA and ZEB1 protein expression levels. Both tumour tissue- and cell culture-derived xenografts recapitulated the vasculoneural paraganglioma structure and arose from mesenchymal-like cells through a fixed developmental sequence. First, vasculoangiogenesis organized the microenvironment, building a perivascular niche which in turn supported neurogenesis. Neuroepithelial differentiation was associated with severe mitochondrial dysfunction, not present in cultured paraganglioma cells, but acquired in vivo during xenograft formation. Vasculogenesis was the Achilles’ heel of xenograft development. In fact, imatinib, that targets endothelial-mural signalling, blocked paraganglioma xenograft formation (11 xenografts from 12 cell transplants in the control group versus 2 out of 10 in the treated group, P = 0.0015). Overall our key results were unaffected by the SDHx gene carrier status of the patient, characterized for 70 out of 77 cases. In conclusion, we explain the biphasic vasculoneural structure of paragangliomas and identify an early and pharmacologically actionable phase of paraganglioma organization. Electronic supplementary material The online version of this article (10.1007/s00401-017-1799-2) contains supplementary material, which is available to authorized users.
- Published
- 2018
23. Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles
- Author
-
Paola Gratteri, Clemente Capasso, Irene Vitale, Giuseppina Bologna, Alessandro Bonardi, Valentina Puca, Claudiu T. Supuran, Paola Lanuti, Viviana De Luca, Pasquale Simeone, Andrea Angeli, Simone Carradori, Alessio Nocentini, and Rossella Grande
- Subjects
Peptic Ulcer ,QH301-705.5 ,carvacrol ,carbonic anhydrase ,Article ,Catalysis ,Helicobacter Infections ,Microbiology ,Inorganic Chemistry ,chemistry.chemical_compound ,Stomach Neoplasms ,Carbonic anhydrase ,Humans ,Carvacrol ,Biology (General) ,Physical and Theoretical Chemistry ,Carbonic Anhydrase Inhibitors ,QD1-999 ,Molecular Biology ,Thymol ,Pathogen ,Spectroscopy ,Carbonic Anhydrases ,chemistry.chemical_classification ,probiotic bacteria ,Helicobacter pylori ,biology ,Organic Chemistry ,Biofilm ,Amoxicillin ,General Medicine ,biology.organism_classification ,molecular modelling ,Anti-Bacterial Agents ,Computer Science Applications ,Chemistry ,Enzyme ,anti-biofilm activity ,chemistry ,Biofilms ,biology.protein ,Cymenes ,Bacterial outer membrane ,Bacterial Outer Membrane Proteins - Abstract
Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.
- Published
- 2021
24. 68P High blood concentration of circulating cancer stem cell-derived extracellular vesicles is associated with poor survival in advanced colorectal cancer patients
- Author
-
Davide Brocco, P. Di Sebastiano, Alessandro Cama, Antonino Grassadonia, P. Di Marino, Marco Marchisio, Paola Lanuti, Giuseppina Bologna, Paola Simeone, L. De Lellis, Nicola Tinari, Sebastiano Miscia, M. De Tursi, and Serena Veschi
- Subjects
Advanced colorectal cancer ,Oncology ,Blood concentration ,Cancer stem cell ,business.industry ,Cancer research ,Medicine ,Hematology ,business ,Extracellular vesicles - Published
- 2021
25. Plasma from obese children increases monocyte-endothelial adhesion and affects intracellular insulin signaling in cultured endothelial cells: Potential role of mTORC1-S6K1
- Author
-
Francesco Chiarelli, Angelika Mohn, Assunta Pandolfi, Carola Palmerini, Caterina Pipino, Nadia Di Pietrantonio, Cosimo Giannini, Maria Pompea Antonia Baldassarre, Giuseppina Bologna, Paola Lanuti, and Natalia Di Pietro
- Subjects
0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,P70-S6 Kinase 1 ,mTORC1 ,Mechanistic Target of Rapamycin Complex 1 ,030204 cardiovascular system & hematology ,Monocytes ,Plasma ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Internal medicine ,Cell Adhesion ,medicine ,Humans ,Insulin ,Obesity ,Endothelial dysfunction ,Child ,Molecular Biology ,Protein kinase B ,Cells, Cultured ,biology ,Chemistry ,Endothelial Cells ,Ribosomal Protein S6 Kinases, 70-kDa ,medicine.disease ,Insulin receptor ,030104 developmental biology ,Endocrinology ,biology.protein ,Molecular Medicine ,Signal transduction ,Signal Transduction - Abstract
Childhood obesity is characterized by the loss of vascular insulin sensitivity along with altered oxidant-antioxidant state and chronic inflammation, which play a key role in the onset of endothelial dysfunction. We previously demonstrated a reduced insulin-stimulated Nitric Oxide (NO) bioavailability in Human Umbilical Vein Endothelial cells (HUVECs) cultured with plasma from obese pre-pubertal children (OB) compared to those cultured with plasma of normal-weight children (CTRL). However, mechanisms underlying endothelial dysfunction in childhood obesity remains poorly understood. Hence, the present study aimed to better investigate these mechanisms, also considering a potential involvement of mammalian Target Of Rapamycin Complex1 (mTORC1)-ribosomal protein S6 Kinase beta1 (S6K1) pathway. OB-children (N = 32, age: 9.2 ± 1.7; BMI z-score: 2.72 ± 0.31) had higher fasting insulin levels and increased HOMA-IR than CTRL-children (N = 32, age: 8.8 ± 1.2; BMI z-score: 0.33 ± 0.75). In vitro, HUVECs exposed to OB-plasma exhibited significant increase in Reactive Oxygen Species (ROS) levels, higher vascular and intercellular adhesion molecules exposure, together with increased monocytes-endothelial interaction. This was associated with unbalanced pro- and anti-atherogenic endothelial insulin stimulated signaling pathways, as measured by increased Mitogen Activated Protein Kinase (MAPK) and decreased Insulin Receptor Substrate-1 (IRS-1)/protein kinase B (Akt)/ endothelial NO Synthase (eNOS) phosphorylation levels, together with augmented S6K1 activation. Interestingly, inhibition of mTORC1-S6K1 pathway using rapamycin significantly restored the IRS-1/Akt/eNOS activation, suggesting a feedback regulation of IRS-1/Akt signal through S6K1. Overall, our in vitro data shed light on new mechanisms underlying the onset of endothelial dysfunction in childhood obesity.
- Published
- 2021
26. Plasma from pre-pubertal obese children impairs insulin stimulated Nitric Oxide (NO) bioavailability in endothelial cells: Role of ER stress
- Author
-
Assunta Pandolfi, Sara Di Silvestre, Paola Lanuti, Giuseppina Bologna, Natalia Di Pietro, Francesco Chiarelli, Vincenzo Giuseppe Pio Cordone, Tommaso de Giorgis, Angelika Mohn, M. Loredana Marcovecchio, Marcovecchio, Loredana [0000-0002-4415-316X], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,medicine.medical_treatment ,Biochemistry ,Umbilical vein ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Insulin ,Endothelial dysfunction ,Phosphorylation ,Child ,Cyclic GMP ,Endoplasmic Reticulum Chaperone BiP ,biology ,NF-kappa B ,Endoplasmic Reticulum Stress ,Protein Transport ,ER stress ,medicine.medical_specialty ,Nitric Oxide Synthase Type III ,Biological Availability ,030209 endocrinology & metabolism ,Models, Biological ,Article ,Nitric oxide ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,Human Umbilical Vein Endothelial Cells ,medicine ,Humans ,Obesity ,Molecular Biology ,Cell Nucleus ,business.industry ,Puberty ,Impaired fasting glucose ,medicine.disease ,Activating Transcription Factor 6 ,Insulin receptor ,030104 developmental biology ,chemistry ,Unfolded protein response ,biology.protein ,business ,Proto-Oncogene Proteins c-akt ,Biomarkers - Abstract
Childhood obesity is commonly associated with early signs of endothelial dysfunction, characterized by impairment of insulin signaling and vascular Nitric Oxide (NO) availability. However, the underlying mechanisms remain to be established. Hence, we tested the hypothesis that endothelial insulin-stimulated NO production and availability was impaired and related to Endoplasmic Reticulum (ER) in human umbilical vein endothelial cells (HUVECs) cultured with plasma obtained from pre-pubertal obese (OB) children. OB children (N = 28, age: 8.8 ± 2.2; BMI z-score: 2.15 ± 0.39) showed impaired fasting glucose, insulin and HOMA-IR than normal weight children (CTRL; N = 28, age: 8.8 ± 1.7; BMI z-score: 0.17 ± 0.96). The in vitro experiments showed that OB-plasma significantly impaired endothelial insulin-stimulated NO production and bioavailability compared to CTRL-plasma. In parallel, in HUVECs OB-plasma increased GRP78 and activated PERK, eIF2α, IkBα and ATF6 (all ER stress markers). Moreover, OB-plasma increased NF-κB activation and its nuclear translocation. Notably, all these effects proved to be significantly restored by using PBA and TUDCA, known ER stress inhibitors. Our study demonstrate for the first time that plasma from obese children is able to induce in vitro endothelial insulin resistance, which is characterized by reduced insulin-stimulated NO production and bioavailability, endothelial ER stress and increased NF-κB activation., Graphical abstract Image 1, Highlights • Plasma from obese children induce in vitro endothelial insulin resistance (IR). • The mechanism involved is the reduced insulin-stimulated NO bioavailability. • In this experimental condition ER stress is associated to endothelial IR. • The additional effect is the increased endothelial inflammation.
- Published
- 2017
27. P-257 Deep polychromatic flow cytometry characterization of circulating endothelial cells in metastatic colorectal cancer patients
- Author
-
Sebastiano Miscia, Alessandro Cama, M. De Tursi, Giuseppina Bologna, Maria Teresa Martino, Davide Brocco, Marco Marchisio, D. Pietro, Paola Lanuti, Nicola Tinari, and Paola Simeone
- Subjects
Oncology ,medicine.diagnostic_test ,Colorectal cancer ,business.industry ,medicine ,Cancer research ,Hematology ,medicine.disease ,business ,Flow cytometry - Published
- 2020
28. Detection and Quantification of eDNA-Associated Bacterial Membrane Vesicles by Flow Cytometry
- Author
-
Christian Celia, Raffaella Muraro, Sebastiano Miscia, Eva Ercolino, Giuseppina Bologna, Paola Lanuti, Gabriella Mincione, Marco Marchisio, Di Marzio L, Puca, and Rossella Grande
- Subjects
0301 basic medicine ,DNA, Bacterial ,Limosilactobacillus reuteri ,030106 microbiology ,Lactobacillus reuteri ,Catalysis ,Article ,biofilm ,Flow cytometry ,lcsh:Chemistry ,Inorganic Chemistry ,03 medical and health sciences ,Extracellular Vesicles ,Fluorescence microscope ,medicine ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,medicine.diagnostic_test ,biology ,Helicobacter pylori ,Chemistry ,Vesicle ,flow cytometry ,Organic Chemistry ,Cell Membrane ,Biofilm ,General Medicine ,biology.organism_classification ,Computer Science Applications ,Staining ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Biochemistry ,Nucleic acid ,extracellular DNA (eDNA) ,bacterial membrane vesicles ,Bacteria - Abstract
Bacteria generate membrane vesicles, which are structures known as extracellular vesicles (EVs), reported to be involved in different pathogenic mechanisms, as it has been demonstrated that EVs participate in biofilm formation, cell-to-cell communication, bacteria–host interactions, and nutrients supply. EVs deliver nucleic acids, proteins, and polysaccharides. It has been reported that Helicobacter pylori (H. pylori) and Lactobacillus reuteri (L. reuteri), of both planktonic and biofilm phenotypes, produce EVs carrying extracellular DNA (eDNA). Here, we used polychromatic flow cytometry (PFC) to identify, enumerate, and characterize EVs as well as the eDNA-delivering EV compartment in the biofilm and planktonic phenotypes of H.pylori ATCC 43629 and L. reuteri DSM 17938. Biofilm formation was demonstrated and analyzed by fluorescence microscopy, using a classical live/dead staining protocol. The enumeration of EVs and the detection of eDNA-associated EVs were performed by PFC, analyzing both whole samples (cells plus vesicles) and EVs isolated by ultracentrifugation confirm EVs isolated by ultracentrifugation. PFC analysis was performed relying on a known-size beaded system and a mix of three different fluorescent tracers. In detail, the whole EV compartment was stained by a lipophilic cationic dye (LCD), which was combined to PKH26 and PicoGreen that selectively stain lipids and DNA, respectively. Fluorescence microscopy results displayed that both H. pylori and L. reuteri produced well-structured biofilms. PFC data highlighted that, in both detected bacterial species, biofilms produced higher EVs counts when paralleled to the related planktonic phenotypes. Furthermore, the staining with PicoGreen showed that most of the generated vesicles were associated with eDNA. These data suggest that the use of PFC, set according to the parameters here described, allows for the study of the production of eDNA-associated EVs in different microbial species in the same or several phases of growth, thus opening new perspectives in the study of microbial derived EVs in clinical samples.
- Published
- 2019
29. An explorative study identifies miRNA signatures for the diagnosis of non-celiac wheat sensitivity
- Author
-
Michele Sallese, Marta Di Nicola, Marco Marchisio, Matteo Neri, Giuseppina Bologna, Vanessa Capone, Konstantinos Efthymakis, Samantha Sperduti, Erminia Carletti, and Emanuela Clemente
- Subjects
0301 basic medicine ,Tissue transglutaminase ,Biopsy ,Disease ,Gastroenterology ,Biochemistry ,0302 clinical medicine ,Mathematical and Statistical Techniques ,Intestinal mucosa ,Medicine and Health Sciences ,chemistry.chemical_classification ,Principal Component Analysis ,Multidisciplinary ,biology ,medicine.diagnostic_test ,Statistics ,Eukaryota ,Plants ,Nucleic acids ,Wheat ,Physical Sciences ,Biomarker (medicine) ,Medicine ,030211 gastroenterology & hepatology ,Anatomy ,Research Article ,medicine.medical_specialty ,Science ,Surgical and Invasive Medical Procedures ,Research and Analysis Methods ,03 medical and health sciences ,Extraction techniques ,Internal medicine ,medicine ,Genetics ,Grasses ,Statistical Methods ,Non-coding RNA ,Pathological ,Nutrition ,Natural antisense transcripts ,Biology and life sciences ,business.industry ,Organisms ,Proteins ,nutritional and metabolic diseases ,Gluten ,RNA extraction ,digestive system diseases ,Gene regulation ,Diet ,Gastrointestinal Tract ,MicroRNAs ,030104 developmental biology ,chemistry ,Multivariate Analysis ,biology.protein ,Intraepithelial lymphocyte ,RNA ,Gene expression ,business ,Digestive System ,Mathematics - Abstract
Non-celiac wheat sensitivity (NCWS), also referred to as non-celiac gluten sensitivity, is a recently described disorder triggered by wheat/gluten ingestion. NCWS elicits a wide range of symptoms including diarrhoea, intestinal discomfort, and fatigue in analogy with other wheat/gluten-related disorders and celiac disease in particular. From the pathological standpoint, NCWS patients only have a slight increase of intraepithelial lymphocytes, while antibodies to tissue transglutaminase (tTG) and villous atrophy, otherwise diagnostic features of celiac disease, are absent. To date, the diagnosis of NCWS relies on symptoms and exclusion of confounding diseases, since biomarkers are not yet available. Here, the expression levels of selected miRNAs were examined in duodenal biopsies and peripheral blood leukocytes collected from newly diagnosed patients with NCWS and, as controls, from patients with celiac disease and gluten-independent gastrointestinal problems. We identified a few miRNAs whose expression is higher in the intestinal mucosa of patients affected by NCWS in comparison to control patients affect by gluten-independent dyspeptic symptoms (Helicobacter pylori-negative) and celiac disease. The present study provided the first evidence that NCWS patients have a characteristic miRNA expression patterns, such peculiarity could be exploited as a biomarker to the diagnosis of this disease.
- Published
- 2019
30. Anti-inflammatory Role of Carotenoids in Endothelial Cells Derived from Umbilical Cord of Women Affected by Gestational Diabetes Mellitus
- Author
-
Paola Lanuti, Pamela Di Tomo, Caterina Pipino, Mariangela Ucci, Gloria Formoso, Federica Tritschler, Domitilla Mandatori, Vincenzo Giuseppe Pio Cordone, Assunta Pandolfi, Giuseppina Bologna, Natalia Di Pietro, and Sara Di Silvestre
- Subjects
Adult ,0301 basic medicine ,Aging ,medicine.medical_specialty ,Article Subject ,Anti-Inflammatory Agents ,Biological Availability ,Vascular Cell Adhesion Molecule-1 ,Cell Communication ,030204 cardiovascular system & hematology ,Nitric Oxide ,medicine.disease_cause ,Biochemistry ,Monocytes ,Nitric oxide ,Flow cytometry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pregnancy ,Peroxynitrous Acid ,Diabetes mellitus ,Internal medicine ,Human Umbilical Vein Endothelial Cells ,medicine ,Humans ,Endothelial dysfunction ,lcsh:QH573-671 ,medicine.diagnostic_test ,Tumor Necrosis Factor-alpha ,business.industry ,lcsh:Cytology ,Transcription Factor RelA ,Cell Biology ,General Medicine ,Intercellular Adhesion Molecule-1 ,medicine.disease ,Carotenoids ,Gestational diabetes ,Diabetes, Gestational ,030104 developmental biology ,Endocrinology ,chemistry ,Female ,Tumor necrosis factor alpha ,business ,Oxidative stress ,Peroxynitrite ,Research Article - Abstract
Diabetes is associated with vascular inflammation, endothelial dysfunction, and oxidative stress, promoting the development of cardiovascular diseases (CVD). Several studies showed that a carotenoid-rich diet is associated to a reduced cardiovascular risk in healthy and diabetic subjects, although the mechanisms of action are still unknown. Here, the potential role of β-carotene (BC) and lycopene (Lyc) in human endothelial cells isolated from human umbilical cord vein (HUVECs) of women with gestational diabetes (GD) and respective controls (C) has been investigated. Results showed that BC and Lyc reduced the tumor necrosis factor alpha- (TNF-α-) stimulated monocyte-endothelium interaction (adhesion assay), membrane exposure (flow cytometry), and total expression levels (Western blot) of VCAM-1 and ICAM-1 in both cell types. Moreover, the treatment with BC and Lyc reduced the TNF-α-induced nuclear translocation of NF-κB (image flow cytometry) by preserving bioavailability of nitric oxide (NO, flow cytometry, and cGMP EIA kit assay), a key vasoactive molecule. Notably, BC and Lyc pretreatment significantly reduced peroxynitrite levels (flow cytometry), contributing to the redox balance protection. These results suggest a new mechanism of action of carotenoids which exert vascular protective action in diabetic condition, thus reinforcing the importance of a carotenoid-rich diet in the prevention of diabetes cardiovascular complications.
- Published
- 2019
31. Predialysis and Dialysis Therapies Differently Affect Nitric Oxide Synthetic Pathway in Red Blood Cells from Uremic Patients: Focus on Peritoneal Dialysis
- Author
-
Giorgia Di Fulvio, Giuseppina Bologna, Domitilla Mandatori, Vittorio Sirolli, Mario Bonomini, Paola Lanuti, Natalia Di Pietro, Marco Marchisio, Carola Palmerini, Luca Piscitani, Chiara Riganti, Lorenzo Di Liberato, Giulia Renda, Caterina Pipino, and Assunta Pandolfi
- Subjects
Male ,Erythrocytes ,medicine.medical_treatment ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Pharmacology ,Kidney Failure ,lcsh:Chemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Models ,cardiovascular disease ,Chronic ,Phosphorylation ,lcsh:QH301-705.5 ,Cyclic GMP ,Spectroscopy ,hemodialysis ,biology ,MRP4 ,General Medicine ,Middle Aged ,Computer Science Applications ,Nitric oxide synthase ,peritoneal dialysis ,Female ,Hemodialysis ,Multidrug Resistance-Associated Proteins ,Cardiovascular disease ,CGMP ,Chronic kidney disease ,Nitric oxide ,Peritoneal dialysis ,Aged ,Humans ,Kidney Failure, Chronic ,Models, Biological ,Nitric Oxide ,Nitric Oxide Synthase ,Nitrites ,Nitrosation ,Uremia ,Peritoneal Dialysis ,Renal Dialysis ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Physical and Theoretical Chemistry ,Molecular Biology ,Cyclic guanosine monophosphate ,Dialysis ,business.industry ,Organic Chemistry ,Biological ,medicine.disease ,cGMP ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,biology.protein ,business ,chronic kidney disease ,Kidney disease - Abstract
Red blood cells (RBCs) have been found to synthesize and release both nitric oxide (NO) and cyclic guanosine monophosphate (cGMP), contributing to systemic NO bioavailability. These RBC functions resulted impaired in chronic kidney disease (CKD). This study aimed to evaluate whether predialysis (conservative therapy, CT) and dialysis (peritoneal dialysis, PD, hemodialysis, HD) therapies used during CKD progression may differently affect NO-synthetic pathway in RBCs. Our data demonstrated that compared to PD, although endothelial-NO-synthase activation was similarly increased, HD and CT were associated to cGMP RBCs accumulation, caused by reduced activity of cGMP membrane transporter (MRP4). In parallel, plasma cGMP levels were increased by both CT and HD and they significantly decreased after hemodialysis, suggesting that this might be caused by reduced cGMP renal clearance. As conceivable, compared to healthy subjects, plasma nitrite levels were significantly reduced by HD and CT but not in patients on PD. Additionally, the increased carotid intima-media thickness (IMT) values did not reach the significance exclusively in patients on PD. Therefore, our results show that PD might better preserve the synthetic NO-pathway in CKD-erythrocytes. Whether this translates into a reduced development of uremic vascular complications requires further investigation.
- Published
- 2021
32. Role of Extracellular Vesicles in Epithelial Ovarian Cancer: A Systematic Review
- Author
-
Sara Tinari, Martina Leombroni, Giovanni Scambia, Francesco D'Antonio, Alessandro Lucidi, Danilo Buca, Giuseppina Bologna, Paola Lanuti, D. Buca, Marco Liberati, Carlo Ronsini, Marco Petrillo, Lucidi, A., Buca, D., Ronsini, C., Tinari, S., Bologna, G., Leombroni, M., Liberati, M., D'Antonio, F., Scambia, G., Lanuti, P., and Petrillo, M.
- Subjects
endocrine system diseases ,Cell Communication ,Review ,Carcinoma, Ovarian Epithelial ,lcsh:Chemistry ,Immunological escape ,RNA, Neoplasm ,lcsh:QH301-705.5 ,Early Detection of Cancer ,Spectroscopy ,Ovarian Neoplasms ,MicroRNA ,General Medicine ,Extracellular vesicles ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,Crosstalk (biology) ,Tumor microenvironment ,Lymphatic Metastasis ,Female ,Extracellular vesicle ,Signal Transduction ,Epithelial-Mesenchymal Transition ,Antineoplastic Agents ,Catalysis ,Inorganic Chemistry ,Immune system ,Ovarian cancer ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Epithelial–mesenchymal transition ,Physical and Theoretical Chemistry ,Molecular Biology ,business.industry ,Organic Chemistry ,medicine.disease ,MicroRNAs ,Settore MED/40 - GINECOLOGIA E OSTETRICIA ,lcsh:Biology (General) ,lcsh:QD1-999 ,Tumor Escape ,Drug Resistance, Neoplasm ,Cancer research ,Epithelial mesenchymal transition ,business - Abstract
Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial–mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients.
- Published
- 2020
33. Human Mesenchymal Stem Cells Reendothelialize Porcine Heart Valve Scaffolds: Novel Perspectives in Heart Valve Tissue Engineering
- Author
-
Paola Lanuti, Francesco Serafini, Laura Pierdomenico, Pasquale Simeone, Giuseppina Bologna, Eva Ercolino, Sara Di Silvestre, Simone Guarnieri, Carlo Canosa, Gianna Gabriella Impicciatore, Stella Chiarini, Francesco Magnacca, Maria Addolorata Mariggiò, Assunta Pandolfi, Marco Marchisio, Gabriele Di Giammarco, and Sebastiano Miscia
- Subjects
Scaffold ,Cell type ,endothelium ,Endothelium ,Regeneration (biology) ,lcsh:R ,Mesenchymal stem cell ,heart valve tissue engineering ,lcsh:Medicine ,Anatomy ,Matrix (biology) ,Biology ,heart valve diseases ,General Biochemistry, Genetics and Molecular Biology ,Umbilical vein ,Cell biology ,WJ-MSCs ,medicine.anatomical_structure ,lcsh:Biology (General) ,medicine ,Original Research Article ,Heart valve ,lcsh:QH301-705.5 - Abstract
Heart valve diseases are usually treated by surgical intervention addressed for the replacement of the damaged valve with a biosynthetic or mechanical prosthesis. Although this approach guarantees a good quality of life for patients, it is not free from drawbacks (structural deterioration, nonstructural dysfunction, and reintervention). To overcome these limitations, the heart valve tissue engineering (HVTE) is developing new strategies to synthesize novel types of valve substitutes, by identifying efficient sources of both ideal scaffolds and cells. In particular, a natural matrix, able to interact with cellular components, appears to be a suitable solution. On the other hand, the well-known Wharton's jelly mesenchymal stem cells (WJ-MSCs) plasticity, regenerative abilities, and their immunomodulatory capacities make them highly promising for HVTE applications. In the present study, we investigated the possibility to use porcine valve matrix to regenerate in vitro the valve endothelium by WJ-MSCs differentiated along the endothelial lineage, paralleled with human umbilical vein endothelial cells (HUVECs), used as positive control. Here, we were able to successfully decellularize porcine heart valves, which were then recellularized with both differentiated-WJ-MSCs and HUVECs. Data demonstrated that both cell types were able to reconstitute a cellular monolayer. Cells were able to positively interact with the natural matrix and demonstrated the surface expression of typical endothelial markers. Altogether, these data suggest that the interaction between a biological scaffold and WJ-MSCs allows the regeneration of a morphologically well-structured endothelium, opening new perspectives in the field of HVTE.
- Published
- 2015
34. Su1924 CIRCULATING EXTRACELLULAR VESICLES CORRELATE WITH DISEASE ACTIVITY AND INFLAMMATION MARKERS IN INFLAMMATORY BOWEL DISEASE PATIENTS
- Author
-
Giuseppina Bologna, Marco Marchisio, Sebastiano Miscia, Matteo Neri, Pasquale Simeone, Lucrezia Viscioni, Konstantinos Efthymakis, Paola Lanuti, and Gianpaolo Lupacchini
- Subjects
Disease activity ,Pathology ,medicine.medical_specialty ,Hepatology ,business.industry ,Gastroenterology ,medicine ,Inflammation ,medicine.symptom ,business ,medicine.disease ,Extracellular vesicles ,Inflammatory bowel disease - Published
- 2020
35. Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers
- Author
-
Daniele Vergara, Sebastiano Miscia, Pasquale Simeone, Paola Lanuti, Marco Marchisio, Giuseppina Bologna, Maria Teresa Guagnano, Laura Pierdomenico, Damiana Pieragostino, Renato Mariani-Costantini, Piero Del Boccio, Simeone, P, Bologna, G, Lanuti, P, Pierdomenico, L, Guagnano, Mt, Pieragostino, D, Del Boccio, P, Vergara, D, Marchisio, M, Miscia, S, and Mariani-Costantini, R.
- Subjects
Review ,Cell Communication ,Biology ,medicine.disease_cause ,Extracellular vesicles ,Catalysis ,lcsh:Chemistry ,Inorganic Chemistry ,Immunity ,medicine ,Humans ,Disease biomarker ,Disease ,Genetic Predisposition to Disease ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,biological barriers ,liquid biopsy ,Organic Chemistry ,biomarkers ,General Medicine ,Computer Science Applications ,Cell biology ,Multicellular organism ,lcsh:Biology (General) ,lcsh:QD1-999 ,Biological significance ,extracellular vesicles ,Carcinogenesis ,Intracellular ,Signal Transduction - Abstract
Extracellular vesicles act as shuttle vectors or signal transducers that can deliver specific biological information and have progressively emerged as key regulators of organized communities of cells within multicellular organisms in health and disease. Here, we survey the evolutionary origin, general characteristics, and biological significance of extracellular vesicles as mediators of intercellular signaling, discuss the various subtypes of extracellular vesicles thus far described and the principal methodological approaches to their study, and review the role of extracellular vesicles in tumorigenesis, immunity, non-synaptic neural communication, vascular-neural communication through the blood-brain barrier, renal pathophysiology, and embryo-fetal/maternal communication through the placenta.
- Published
- 2020
36. Corrigendum to 'Circulating Cancer Stem Cell-Derived Extracellular Vesicles as a Novel Biomarker for Clinical Outcome Evaluation'
- Author
-
Paola Lanuti, Maria Concetta Cufaro, P. Di Marino, P. Del Boccio, Antonino Grassadonia, Giuseppina Bologna, Marco Marchisio, Marta Peri, I. G. Rapposelli, Clara Natoli, Vincenzo Graziano, Laura Pierdomenico, Davide Brocco, Fausta Ciccocioppo, Paola Simeone, Sebastiano Miscia, Nicola Tinari, Damiana Pieragostino, M. De Tursi, Eva Ercolino, Grassadonia, A [0000-0002-2459-0661], Del Boccio, P [0000-0003-1653-2194], Marchisio, M [0000-0003-3058-3422], Natoli, C [0000-0001-7295-0230], and Apollo - University of Cambridge Repository
- Subjects
business.industry ,education ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,32 Biomedical and Clinical Sciences ,3211 Oncology and Carcinogenesis ,Extracellular vesicles ,Oncology ,Cancer stem cell ,Cancer research ,Biomarker (medicine) ,Medicine ,Corrigendum ,business ,RC254-282 - Abstract
[This corrects the article DOI: 10.1155/2019/5879616.].
- Published
- 2020
37. P1.09 Circulating Cancer Stem Cell-Derived Extracellular Vesicles as a Novel Biomarker for Clinical Outcome Evaluation in NSCLC
- Author
-
N. Tinari, Luciana Irtelli, Davide Brocco, Paola Simeone, P. Di Marino, Giuseppina Bologna, Paola Lanuti, Marco Marchisio, M. De Tursi, Marta Peri, and Sebastiano Miscia
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Cancer stem cell ,business.industry ,Cancer research ,Medicine ,Biomarker (medicine) ,business ,Extracellular vesicles - Published
- 2019
38. A standardized flow cytometry network study for the assessment of circulating endothelial cell physiological ranges
- Author
-
Gianluca Rotta, Paola Lanuti, Elena Di Gennaro, Natalia Malara, Alfredo Budillon, Mirella Marini, Pasquale Mastroroberto, Valentina Trunzo, Francesca Losa, Silvia Pinna, Maria Cristina Tirindelli, Marco Marchisio, Paolo Doretto, Alessandra Falda, Emma Muggianu, Lorenza Scotti, Camillo Almici, Giuseppe Musolino, Annamaria Diodato, Carlo Vitagliano, Laura Pierdomenico, Fulvio Zullo, Rosa Azzaro, Sebastiano Miscia, María Roca, Melania Di Cerbo, Domenico Russo, Chiara Gregorj, Michele Morelli, Vincenzo Mollace, Arabella Neva, Giovanna Piovani, Pasquale Simeone, Giuseppe Avvisati, Eva Ercolino, Alessandra Leone, Roberta Venturella, Maria Luisa Di Martino, Giuseppina Bologna, Lanuti, P, Simeone, P, Rotta, G, Almici, C, Avvisati, G, Azzaro, R, Bologna, G, Budillon, A, Di Cerbo, M, Di Gennaro, E, Di Martino, M, Diodato, A, Doretto, P, Ercolino, E, Falda, A, Gregorj, C, Leone, A, Losa, F, Malara, N, Marini, M, Mastroroberto, P, Mollace, V, Morelli, M, Muggianu, E, Musolino, G, Neva, A, Pierdomenico, L, Pinna, S, Piovani, G, Roca, M, Russo, D, Scotti, L, Tirindelli, M, Trunzo, V, Venturella, R, Vitagliano, C, Zullo, F, Marchisio, M, Miscia, S, Lanuti, Paola, Simeone, Pasquale, Rotta, Gianluca, Almici, Camillo, Avvisati, Giuseppe, Azzaro, Rosa, Bologna, Giuseppina, Budillon, Alfredo, Di Cerbo, Melania, Di Gennaro, Elena, Di Martino, Maria Luisa, Diodato, Annamaria, Doretto, Paolo, Ercolino, Eva, Falda, Alessandra, Gregorj, Chiara, Leone, Alessandra, Losa, Francesca, Malara, Natalia, Marini, Mirella, Mastroroberto, Pasquale, Mollace, Vincenzo, Morelli, Michele, Muggianu, Emma, Musolino, Giuseppe, Neva, Arabella, Pierdomenico, Laura, Pinna, Silvia, Piovani, Giovanna, Roca, Maria Serena, Russo, Domenico, Scotti, Lorenza, Tirindelli, Maria Cristina, Trunzo, Valentina, Venturella, Roberta, Vitagliano, Carlo, Zullo, Fulvio, Marchisio, Marco, and Miscia, Sebastiano
- Subjects
Adult ,Male ,0301 basic medicine ,Median Fluorescence Intensity ,Circulating endothelial cell ,Science ,Large population ,Cell Separation ,Biology ,Sensitivity and Specificity ,Article ,Flow cytometry ,Andrology ,Young Adult ,03 medical and health sciences ,Reference Values ,medicine ,Humans ,High potential ,Multidisciplinary ,medicine.diagnostic_test ,Healthy population ,Endothelial Cells ,Hematology ,Middle Aged ,Flow Cytometry ,Healthy Volunteers ,Peripheral blood ,Blood Cell Count ,030104 developmental biology ,Biological Variation, Population ,cardiovascular system ,Feasibility Studies ,Medicine ,Female ,Endothelium, Vascular ,Laboratories ,Biological variability - Abstract
Circulating endothelial cells (CEC) represent a restricted peripheral blood (PB) cell subpopulation with high potential diagnostic value in many endothelium-involving diseases. However, whereas the interest in CEC studies has grown, the standardization level of their detection has not. Here, we undertook the task to align CEC phenotypes and counts, by standardizing a novel flow cytometry approach, within a network of six laboratories. CEC were identified as alive/nucleated/CD45negative/CD34bright/CD146positive events and enumerated in 269 healthy PB samples. Standardization was demonstrated by the achievement of low inter-laboratory Coefficients of Variation (CVL), calculated on the basis of Median Fluorescence Intensity values of the most stable antigens that allowed CEC identification and count (CVL of CD34bright on CEC ~ 30%; CVL of CD45 on Lymphocytes ~ 20%). By aggregating data acquired from all sites, CEC numbers in the healthy population were captured (medianfemale = 9.31 CEC/mL; medianmale = 11.55 CEC/mL). CEC count biological variability and method specificity were finally assessed. Results, obtained on a large population of donors, demonstrate that the established procedure might be adopted as standardized method for CEC analysis in clinical and in research settings, providing a CEC physiological baseline range, useful as starting point for their clinical monitoring in endothelial dysfunctions.
- Published
- 2018
39. Su1167 - Total Annexin V+ Circulating Microvesicles Differentiate Non Celiac Gluten Sensitivity from Celiac Disease Patients and Healthy Controls
- Author
-
Antonella Bonitatibus, Konstantinos Efthymakis, Matteo Neri, Pasquale Simeone, Angelo Milano, Francesco Laterza, Eleonora Insolia, Paola Lanuti, Assunta Pandolfi, Sebastiano Miscia, Giuseppina Bologna, Caterina Pipino, and Marco Marchisio
- Subjects
Hepatology ,business.industry ,Annexin ,Immunology ,Gastroenterology ,Medicine ,Disease ,business ,medicine.disease ,Non-celiac gluten sensitivity ,Microvesicles - Published
- 2018
40. Su1172 - Circulating Microvesicle Patterns are Different Between Non Celiac Gluten Sensitivity Patients and Healthy Controls
- Author
-
Assunta Pandolfi, Sebastiano Miscia, Marco Marchisio, Matteo Neri, Eleonora Insolia, Antonella Bonitatibus, Pasquale Simeone, Giuseppina Bologna, Caterina Pipino, Paola Lanuti, Konstantinos Efthymakis, Angelo Milano, and Francesco Laterza
- Subjects
Hepatology ,business.industry ,Immunology ,Gastroenterology ,Medicine ,business ,medicine.disease ,Non-celiac gluten sensitivity ,Circulating microvesicle - Published
- 2018
41. Correction to: Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib
- Author
-
Andrea D’Argenio, Renato Mariani-Costantini, Alessandro Cama, Lorenzo Tramontana, Mattia Russel Pantalone, Mario Sanna, Diana L. Esposito, Vinagolu K. Rajasekhar, Rosalba Florio, Simone Guarnieri, Cecilia Söderberg-Nauclér, Cosmo Rossi, Lavinia Vittoria Lotti, Paola Lanuti, Francesca Schiavi, Silvia Perconti, Rosa Visone, Annalisa Morgano, Artenca Sheu, Giuseppina Bologna, Sampath Chandra Prasad, Elisa Taschin, Carlo Terenzio Paties, Fabio Verginelli, Giuseppe Opocher, Simone Vespa, Angelo Veronese, and Marco Marchisio
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Published Erratum ,MEDLINE ,Imatinib ,Spelling ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,Internal medicine ,medicine ,Neurology (clinical) ,business ,medicine.drug - Abstract
The given and family names of two co-authors were incorrect in the published article. The correct spelling should read as: Sampath Chandra Prasad and Vinagolu K Rajasekhar.
- Published
- 2018
42. Circulating Extracellular Vesicles, A Novel Mechanism of Endocrine Cellular Cross-Talk, are Increased in Newly Diagnosed Celiac Disease Patients
- Author
-
Antonella Bonitatibus, Angelo Milano, Marco Marchisio, Paola Lanuti, Konstantinos Efthymakis, Giuseppina Bologna, Matteo Neri, Pasquale Simeone, Sebastiano Miscia, and Francesco Laterza
- Subjects
Pathology ,medicine.medical_specialty ,Hepatology ,Mechanism (biology) ,business.industry ,Gastroenterology ,Medicine ,Endocrine system ,Newly diagnosed ,Disease ,business ,Extracellular vesicles - Published
- 2017
43. Cryopreservation Effects on Wharton’s Jelly Stem Cells Proteome
- Author
-
Marco Marchisio, Marco Gesi, Marilisa Sulpizio, Paola Lanuti, Laura Pierdomenico, Sebastiano Miscia, F. Di Giuseppe, Stefania Angelucci, Giuseppina Bologna, A Riviello, Enrica Eleuterio, and C Di Ilio
- Subjects
Cryopreservation ,Cancer Research ,Adipogenesis ,Proteome ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Cell Separation ,Cell Biology ,Telomere ,Biology ,Regenerative medicine ,Umbilical Cord ,Cell biology ,Cell therapy ,Transplantation ,Tissue engineering ,Antigens, CD ,Osteogenesis ,Cell culture ,Wharton's jelly ,Humans ,Protein Interaction Maps ,Stem cell ,Cells, Cultured - Abstract
Cryopreservation is the only method for long-term storage of viable cells and tissues used for cellular therapy, stem cell transplantation and/or tissue engineering. However, the freeze-thaw process strongly contributes to cell and tissue damage through several mechanisms, including oxidative stress, cell injury from intracellular ice formation and altered physical cellular properties. Our previous proteomics investigation was carried out on Wharton's Jelly Stem Cells (WJSCs) having similar properties to adult mesenchymal stem cells and thus representing a rich source of primitive cells to be potentially used in regenerative medicine. The aim of the present work was to investigate molecular changes that occur in WJSCs proteome in different experimental conditions: fresh primary cell culture and frozen cell. To analyze changes in protein expression of WJSCs undergoing different culturing procedures, we performed a comparative proteomic analysis (2DE followed by MALDI-TOF MS/MS nanoESI-Q-TOF MS coupled with nanoLC) between WJSCs from fresh and frozen cell culturing, respectively. Frozen WJSCs showed qualitative and quantitative changes compared to cells from fresh preparation, expressing proteins involved in replication, cellular defence mechanism and metabolism, that could ensure freeze-thaw survival. The results of this study could play a key role in elucidating possible mechanisms related to maintaining active proliferation and maximal cellular plasticity and thus making the use of WJSCs in cell therapy safe following bio-banking.
- Published
- 2014
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.