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1. Stem Cell Delivery Routes: From Preclinical Models to Clinical Applications

Author

Fagoonee, Sharmila

Subjects
Stem Cell Bioengineering, Stem Cell Technology, Extracellular vesicles, Mouse stem cell models, Stem Cell transplantation, Cell transplantation, Medical Biotechnology, Secretome, Cell-based therapeutics, stem cell tracking, Genetic engineering, tissue engineering, Cell-free therapy, biomaterials, Transplantation routes, cell delivery, liver stem cells, cornea transplant, kidney transplants, regenerative medicine
Abstract

Stem Cell Delivery Routes: From Preclinical Models to Clinical Applications covers current knowledge about stem cell delivery for cell-based therapeutics. Starting with an introduction to stem cell technology, the book provides information about the main mesenchymal stem cell (MSC) delivery routes and the cell carrier materials used for delivering the cells. The main delivery routes include the liver, the kidney and the ocular surface. This introductory information is followed up with general information about stem cell based therapeutics, covering relevant topics such as the secretome and optimal delivery strategies in cell-based therapeutics. The book then progresses into the topic of in vivo cell tracking methods in preclinical and clinical studies with specific emphasis on the liver, ocular surface and kidney while also covering factors that affect the residence time, viability, and homing of MSCs with respect to the targeted location. The discussions in these chapters are accompanied by key descriptions of MSC-based therapeutic applications in rodent models and human clinical studies. The advantages and bottlenecks in clinical MSC application, and ways to improve the therapeutic efficacy of transplanted cells are also presented, rounding up the contents of the book. Key Feature: - A comprehensive summary of stem cell delivery for cell-based therapeutics, suitable for a broad range of readers - 10 sequential chapters that enhance the reader’s understanding on the subject - An Introduction to stem cell technology - Coverage of 3 key stem cell transplantation routes (liver, kidney and eye) - Coverage of in vivo stem cell tracking - Inclusion of basic information about MSC delivery and methods of clinical applications - Discussions about preclinical mouse models - A perspective on stem cell bottlenecks and recent advances in biomedical engineering that enhance the clinical application of MSCs The contents are adapted to suit readers learning about advanced stem cells therapies at all academic levels, including undergraduates, lecturers, as well as those who are curious to understand more about the importance of stem cells, and their application in cell-based therapeutics. Professionals involved in allied fields in clinical research, and biomedical engineering will also gain a substantial understanding about regenerative medicine and cell transplantation.

Published
2021
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4. Extracellular Vesicle-Enclosed Oxidative Stress- and Inflammation-Related microRNAs as Potential Biomarkers of Vitamin D Responsivity: A Pilot Study on Inflammatory Bowel Disease Patients with or without COVID-19.

Author

Ammirata, Giorgia, Arigoni, Maddalena, Licastro, Danilo, Caviglia, Gian Paolo, Disabato, Michela, Zubair, Ghania, Bezzio, Cristina, Saibeni, Simone, De Nicolò, Amedeo, Cusato, Jessica, Palermiti, Alice, Manca, Alessandra, Tolosano, Emanuela, Cozzini, Stefano, Mancini, Marcello, Altruda, Fiorella, D'Avolio, Antonio, Ribaldone, Davide Giuseppe, Ala, Ugo, and Fagoonee, Sharmila

Subjects
INFLAMMATORY bowel diseases, CROHN'S disease, COVID-19, TRANSFER RNA, VIRUS diseases
Abstract

The relationship between serum 25-hydroxyvitamin D (25(OH)D) levels, genomic response to vitamin D (Vit.D), and positivity to SARS-CoV-2 remains understudied. In this pilot study, during the follow-up of patients with Inflammatory Bowel Disease (IBD) and COVID-19, we investigated this issue by analyzing the molecular contents of serum extracellular vesicles (EVs) from six groups of IBD patients (n = 32), classified according to anti-SARS-CoV-2 status, 25(OH)D level, and Vit.D supplementation, by small RNA-seq. This analysis revealed differentially expressed miRNAs, PIWI-RNA, transfer RNA, small nucleolar RNAs, and protein-coding RNAs in the EVs obtained from these cohorts of IBD patients. Experimental validation evidenced a statistically significant increase in miR30d-5p, miR150-5p, Let-7f-5p, and Let-7a-5p in the anti-SARS-CoV-2-positive and low 25(OH)D and Vit.D supplemented groups with respect to the non-Vit.D supplemented group, indicating their responsiveness to Vit.D treatment. Bioinformatics analysis highlighted the regulation of these validated miRNAs by oxidative stress and inflammation, hallmarks of IBD and COVID-19. Our study reports an unprecedented panel of circulating EV-enclosed inflammation- and oxidative stress-related miRNAs, the potentiality of which, as biomarkers for Vit.D responsivity in IBD patients, needs to be explored in future studies on larger cohorts in order to allow clinicians to optimize current treatment strategies upon viral infection. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Extracellular Vesicles as Delivery Vehicles for Non-Coding RNAs: Potential Biomarkers for Chronic Liver Diseases.

Author

Ferro, Arianna, Saccu, Gabriele, Mattivi, Simone, Gaido, Andrea, Herrera Sanchez, Maria Beatriz, Haque, Shafiul, Silengo, Lorenzo, Altruda, Fiorella, Durazzo, Marilena, and Fagoonee, Sharmila

Subjects
NON-coding RNA, LIVER diseases, HEPATIC fibrosis, LINCRNA, EXTRACELLULAR vesicles
Abstract

In recent years, EVs have emerged as promising vehicles for coding and non-coding RNAs (ncRNAs), which have demonstrated remarkable potential as biomarkers for various diseases, including chronic liver diseases (CLDs). EVs are small, membrane-bound particles released by cells, carrying an arsenal of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA species, such as piRNAs, circRNAs, and tsRNAs. These ncRNAs act as key regulators of gene expression, splicing, and translation, providing a comprehensive molecular snapshot of the cells of origin. The non-invasive nature of EV sampling, typically via blood or serum collection, makes them highly attractive candidates for clinical biomarker applications. Moreover, EV-encapsulated ncRNAs offer unique advantages over traditional cell-free ncRNAs due to their enhanced stability within the EVs, hence allowing for their detection in circulation for extended periods and enabling more sensitive and reliable biomarker measurements. Numerous studies have investigated the potential of EV-enclosed ncRNAs as biomarkers for CLD. MiRNAs, in particular, have gained significant attention due to their ability to rapidly respond to changes in cellular stress and inflammation, hallmarks of CLD pathogenesis. Elevated levels of specific miRNAs have been consistently associated with various CLD subtypes, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and chronic hepatitis B and C. LncRNAs have also emerged as promising biomarkers for CLD. These transcripts are involved in a wide range of cellular processes, including liver regeneration, fibrosis, and cancer progression. Studies have shown that lncRNA expression profiles can distinguish between different CLD subtypes, providing valuable insights into disease progression and therapeutic response. Promising EV-enclosed ncRNA biomarkers for CLD included miR-122 (elevated levels of miR-122 are associated with MASLD progression and liver fibrosis), miR-21 (increased expression of miR-21 is linked to liver inflammation and fibrosis in CLD patients), miR-192 (elevated levels of miR-192 are associated with more advanced stages of CLD, including cirrhosis and HCC), LncRNA HOTAIR (increased HOTAIR expression is associated with MASLD progression and MASH development), and LncRNA H19 (dysregulation of H19 expression is linked to liver fibrosis and HCC progression). In the present review, we focus on the EV-enclosed ncRNAs as promising tools for the diagnosis and monitoring of CLD of various etiologies. [ABSTRACT FROM AUTHOR]

Published
2024
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9. MicroRNA-22 Is a Key Regulator of Lipid and Metabolic Homeostasis

Author

Panella, Riccardo, primary, Petri, Andreas, additional, Desai, Bhavna N., additional, Fagoonee, Sharmila, additional, Cotton, Cody A., additional, Nguyen, Piercen K., additional, Lundin, Eric M., additional, Wagshal, Alexandre, additional, Wang, Da-Zhi, additional, Näär, Anders M., additional, Vlachos, Ioannis S., additional, Maratos-Flier, Eleftheria, additional, Altruda, Fiorella, additional, Kauppinen, Sakari, additional, and Paolo Pandolfi, Pier, additional

Published
2023
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12. Autoimmune Hepatitis and Fibrosis

Author

Pellicano, Rinaldo, primary, Ferro, Arianna, additional, Cicerchia, Francesca, additional, Mattivi, Simone, additional, Fagoonee, Sharmila, additional, and Durazzo, Marilena, additional

Published
2023
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13. Bone Marrow Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles Promote Corneal Wound Repair by Regulating Inflammation and Angiogenesis

Author

Saccu, Gabriele, primary, Menchise, Valeria, additional, Gai, Chiara, additional, Bertolin, Marina, additional, Ferrari, Stefano, additional, Giordano, Cristina, additional, Manco, Marta, additional, Dastrù, Walter, additional, Tolosano, Emanuela, additional, Bussolati, Benedetta, additional, Calautti, Enzo, additional, Camussi, Giovanni, additional, Altruda, Fiorella, additional, and Fagoonee, Sharmila, additional

Published
2022
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15. Expression of SARS-Cov-2 Entry Factors in Patients with Chronic Hepatitis

Author

Rosso, Chiara, primary, Demelas, Cristina, additional, Agostini, Greta, additional, Abate, Maria Lorena, additional, Vernero, Marta, additional, Caviglia, Gian Paolo, additional, D’Amato, Daphne, additional, Armandi, Angelo, additional, Tapparo, Marta, additional, Guariglia, Marta, additional, Troshina, Giulia, additional, Massano, Alessandro, additional, Olivero, Antonella, additional, Nicolosi, Aurora, additional, Zannetti, Antonella, additional, Pellicano, Rinaldo, additional, Ciancio, Alessia, additional, Saracco, Giorgio Maria, additional, Ribaldone, Davide Giuseppe, additional, Bugianesi, Elisabetta, additional, and Fagoonee, Sharmila, additional

Published
2022
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18. Impact of Macroscopic On-Site Evaluation (MOSE) on Accuracy of Endoscopic Ultrasound-Guided Fine-Needle Biopsy (EUS-FNB) of Pancreatic and Extrapancreatic Solid Lesions: A Prospective Study

Author

Gaia, Silvia, primary, Rizza, Stefano, additional, Bruno, Mauro, additional, Ribaldone, Davide Giuseppe, additional, Maletta, Francesca, additional, Sacco, Marco, additional, Pacchioni, Donatella, additional, Rizzi, Felice, additional, Saracco, Giorgio Maria, additional, Fagoonee, Sharmila, additional, and De Angelis, Claudio Giovanni, additional

Published
2022
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21. Phytochemicals from Indian ethnomedicines

Author

Fatima, Nishat, Baqri, Syed Shabihe Raza, Alsulimani, Ahmad, Fagoonee, Sharmila, Slama, Petr, Kesari, Kavindra Kumar, Roychoudhury, Shubhadeep, Haque, Shafiul, Shia PG College, Jazan University, CNR-ENEA-EURATOM Association, Mendel University in Brno, Department of Applied Physics, Assam University, Aalto-yliopisto, and Aalto University

Subjects
Oxidative stress, Phytochemicals, ROS, Ethnomedicine, Cancer
Abstract

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Oxygen is indispensable for most organisms on the earth because of its role in respiration. However, it is also associated with several unwanted effects which may sometimes prove fatal in the long run. Such effects are more evident in cells exposed to strong oxidants containing reactive oxygen species (ROS). The adverse outcomes of oxidative metabolism are referred to as oxidative stress, which is a staple theme in contemporary medical research. Oxidative stress leads to plasma membrane disruption through lipid peroxidation and has several other deleterious effects. A large body of literature suggests the involvement of ROS in cancer, ageing, and several other health haz-ards of the modern world. Plant-based cures for these conditions are desperately sought after as supposedly safer alternatives to mainstream medicines. Phytochemicals, which constitute a diverse group of plant-based substances with varying roles in oxidative reactions of the body, are impli-cated in the treatment of cancer, aging, and all other ROS-induced anomalies. This review presents a summary of important phytochemicals extracted from medicinal plants which are a part of Indian ethnomedicine and Ayurveda and describes their possible therapeutic significance.

Published
2021

28. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice

Author

Porporato, Paolo E., Filigheddu, Nicoletta, Reano, Simone, Ferrara, Michele, Angelino, Elia, Gnocchi, Viola F., Prodam, Flavia, Ronchi, Giulia, Fagoonee, Sharmila, Fornaro, Michele, Chianale, Federica, Baldanzi, Gianluca, Surico, Nicola, Sinigaglia, Fabiola, Perroteau, Isabelle, Smith, Roy G., Sun, Yuxiang, Geuna, Stefano, and Graziani, Andrea

Subjects
Ghrelin -- Physiological aspects -- Genetic aspects -- Research, Cachexia -- Risk factors -- Genetic aspects -- Diagnosis -- Care and treatment -- Research, Atrophy, Muscular -- Risk factors -- Genetic aspects -- Diagnosis -- Care and treatment -- Research, Health care industry
Abstract

Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghrelin is a peptide hormone that stimulates growth hormone (GH) release and positive energy balance through binding to the receptor GHSR-1a. Only acylated ghrelin (AG), but not the unacylated form (UnAG), can bind GHSR-1a; however, UnAG and AG share several GHSR-1a-independent biological activities. Here we investigated whether UnAG and AG could protect against skeletal muscle atrophy in a GHSR-1a-independent manner. We found that both AG and UnAG inhibited dexamethasone-induced skeletal muscle atrophy and atrogene expression through PI3Kβ-, mTORC2-, and p38-mediated pathways in myotubes. Upregulation of circulating UnAG in mice impaired skeletal muscle atrophy induced by either fasting or denervation without stimulating muscle hypertrophy and GHSR-1a-mediated activation of the GH/IGF-1 axis. In Ghsr-deficient mice, both AG and UnAG induced phosphorylation of Akt in skeletal muscle and impaired fasting-induced atrophy. These results demonstrate that AG and UnAG act on a common, unidentified receptor to block skeletal muscle atrophy in a GH-independent manner., Introduction Skeletal muscle atrophy involves massive loss of muscle structural proteins, which leads to muscle weight decrease and progressive loss of muscle function. Skeletal muscle atrophy is induced by muscle [...]

Published
2013
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29. The mitochondrial heme exporter Flvcr1b mediates erythroid differentiation

Author

Chiabrando, Deborah, Marro, Samuele, Mercurio, Sonia, Giorgi, Carlotta, Petrillo, Sara, Vinchi, Francesca, Fiorito, Veronica, Fagoonee, Sharmila, Camporeale, Annalisa, Turco, Emilia, Merlo, Giorgio R., Silengo, Lorenzo, Altruda, Fiorella, Pinton, Paolo, and Tolosano, Emanuela

Subjects
Heme -- Properties, Erythrocytes -- Genetic aspects, Mitochondria -- Properties, Cell differentiation -- Genetic aspects, Health care industry
Abstract

Feline leukemia virus subgroup C receptor 1 (FLVCR1) is a cell membrane heme exporter that maintains the balance between heme levels and globin synthesis in erythroid precursors. It was previously shown that Flvcr1-null mice died in utero due to a failure of erythropoiesis. Here, we identify Flvcr1b, a mitochondrial Flvcr1 isoform that promotes heme efflux into the cytoplasm. Flvcr1b overexpression promoted heme synthesis and in vitro erythroid differentiation, whereas silencing of Flvcr1b caused mitochondrial heme accumulation and termination of erythroid differentiation. Furthermore, mice lacking the plasma membrane isoform (Flvcr1a) but expressing Flvcr1b had normal erythropoiesis, but exhibited hemorrhages, edema, and skeletal abnormalities. Thus, FLVCR1b regulates erythropoiesis by controlling mitochondrial heme efflux, whereas FLVCR1a expression is required to prevent hemorrhages and edema. The aberrant expression of Flvcr1 isoforms may play a role in the pathogenesis of disorders characterized by an imbalance between heme and globin synthesis., Introduction Erythropoiesis is a tightly controlled process regulated by both systemic and cellular signals. Among the latter, heme plays a crucial role not only because it is an essential structural [...]

Published
2012
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31. Anxiety and Gastrointestinal Symptoms Related to COVID-19 during Italian Lockdown

Author

Abenavoli, Ludovico, primary, Cinaglia, Pietro, additional, Lombardo, Giuditta, additional, Boffoli, Eduardo, additional, Scida, Miriam, additional, Procopio, Anna Caterina, additional, Larussa, Tiziana, additional, Boccuto, Luigi, additional, Zanza, Christian, additional, Longhitano, Yaroslava, additional, Fagoonee, Sharmila, additional, and Luzza, Francesco, additional

Published
2021
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32. Higher Efficiency of Percutaneous Microwave (MWA) Than Radiofrequency Ablation (RFA) in Achieving Complete Response in Cirrhotic Patients with Early Hepatocellular Carcinoma

Author

Gaia, Silvia, primary, Ciruolo, Michela, additional, Ribaldone, Davide Giuseppe, additional, Rolle, Emanuela, additional, Migliore, Enrica, additional, Mosso, Elena, additional, Vola, Simone, additional, Risso, Alessandra, additional, Fagoonee, Sharmila, additional, Saracco, Giorgio Maria, additional, and Carucci, Patrizia, additional

Published
2021
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33. Primary Biliary Cholangitis and Bile Acid Farnesoid X Receptor Agonists

Author

Abenavoli, L, Procopio, A, Fagoonee, S, Pellicano, R, Carbone, M, Luzza, F, Invernizzi, P, Abenavoli, Ludovico, Procopio, Anna Caterina, Fagoonee, Sharmila, Pellicano, Rinaldo, Carbone, Marco, Luzza, Francesco, Invernizzi, Pietro, Abenavoli, L, Procopio, A, Fagoonee, S, Pellicano, R, Carbone, M, Luzza, F, Invernizzi, P, Abenavoli, Ludovico, Procopio, Anna Caterina, Fagoonee, Sharmila, Pellicano, Rinaldo, Carbone, Marco, Luzza, Francesco, and Invernizzi, Pietro

Abstract

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by the progressive destruction of the intrahepatic bile ducts. Currently, the first line drug for PBC is ursodeoxycholic acid (UDCA) characterized by anti-apoptotic, anti-inflammatory and protective actions on cholangiocytes. Despite its recognized therapeutic action, 30-40% of PBC patients only partially benefit from UDCA therapy. This has led to the identification of the role of the farnesoid x receptor (FXR) in cholestatic liver diseases and, consequently, to the development of obeticholic acid (OCA), a steroid FXR agonist that has been recently approved for the treatment of PBC. OCA though is not effective in all patients and can cause itch, which eventually induces treatment drop out. Therefore, the search for new therapeutic strategies for PBC has begun. This review, in addition to summarizing the current treatments for PBC, provides overview of the chemical characteristics of new steroid FXR agonist candidates that could represent a future perspective for the treatment of PBC.

Published
2020

38. Clinical Response and Changes of Cytokines and Zonulin Levels in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Treated with Bifidobacterium Longum ES1 for 8 or 12 Weeks: A Preliminary Report

Author

Caviglia, Gian Paolo, primary, Tucci, Alessandra, additional, Pellicano, Rinaldo, additional, Fagoonee, Sharmila, additional, Rosso, Chiara, additional, Abate, Maria Lorena, additional, Olivero, Antonella, additional, Armandi, Angelo, additional, Vanni, Ester, additional, Saracco, Giorgio Maria, additional, Bugianesi, Elisabetta, additional, Astegiano, Marco, additional, and Ribaldone, Davide Giuseppe, additional

Published
2020
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41. Serum Interleukin-6 and -8 as Predictors of Response to Vedolizumab in Inflammatory Bowel Diseases

Author

Bertani, Lorenzo, primary, Caviglia, Gian Paolo, additional, Antonioli, Luca, additional, Pellicano, Rinaldo, additional, Fagoonee, Sharmila, additional, Astegiano, Marco, additional, Saracco, Giorgio Maria, additional, Bugianesi, Elisabetta, additional, Blandizzi, Corrado, additional, Costa, Francesco, additional, and Ribaldone, Davide Giuseppe, additional

Published
2020
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42. On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

Author

Caviglia, Gian, primary, Rosso, Chiara, additional, Stalla, Francesco, additional, Rizzo, Martina, additional, Massano, Alessandro, additional, Abate, Maria, additional, Olivero, Antonella, additional, Armandi, Angelo, additional, Vanni, Ester, additional, Younes, Ramy, additional, Fagoonee, Sharmila, additional, Pellicano, Rinaldo, additional, Astegiano, Marco, additional, Saracco, Giorgio, additional, Bugianesi, Elisabetta, additional, and Ribaldone, Davide, additional

Published
2020
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49. Older age and HDL-cholesterol as independent predictors of liver fibrosis assessed by BARD score

Author

Klisić, Aleksandra, Klisić, Aleksandra, Abenavoli, Ludovico, Fagoonee, Sharmila, Kavarić, Nebojša, Kocić, Gordana, Ninić, Ana, Klisić, Aleksandra, Klisić, Aleksandra, Abenavoli, Ludovico, Fagoonee, Sharmila, Kavarić, Nebojša, Kocić, Gordana, and Ninić, Ana

Abstract

BACKGROUND: It is known that non-alcoholic fatty liver disease (NAFLD), and in particular non-alcoholic steatohepatitis, can progress to advanced fibrosis. However, pathophysiological mechanisms implicated in this evolution are not elucidated yet. We aimed to investigate the independent predictors of liver fibrosis in patients with NAFLD, determined by BARD score, one of the most used algorithms for fibrosis evaluation. METHODS: This prospective study enrolled a total of 301 participants with NAFLD, as determined by a Fatty Liver Index (FLI) >= 60. All patients were categorized into two groups: with no/mild fibrosis (BARD score 1, N.=62) and with advanced fibrosis (BARD score 2, 3 and 4 N.=239). RESULTS: Serum high density lipoprotein cholesterol (HDL-c), glucose and glycated hemoglobin were higher (P=0.028, P lt 0.001 and P=0.002, respectively), whereas serum transaminases and gamma glutamil transferase levels were lower in patients with advanced fibrosis than in those with no/ mild fibrosis (P=0.010, P lt 0.001 and P=0.005, respectively). There were no significant differences in oxidative stress (i.e., advanced oxidant protein products and malondialdehyde) and anti-oxidative protection markers (i.e., catalase) between patients with no/ mild fibrosis and advanced fibrosis. Multivariate ordinal regression analysis showed independent associations and predictions of ages (OR=1.071, 95% CI 1.004-1.097, P lt 0.001), and HDL-c levels (OR= 2.549, 95% CI 1.087-5.989, P=0.032) on BARD score categories in patients with NAFLD. CONCLUSIONS: In conclusion, we found that older age and higher HDL-c, are independent predictors for advanced liver fibrosis assessed with the BARD score. Future investigations are needed to further explore this relationship.

Published
2019

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