Article
Chemistry, Medicinal
Hina Siddiqui, Sarah Shafi, Hamad Ali, Syed Ghulam Musharraf
Summary: The study showed that the newly synthesized thiourea derivatives 1-27 have potential as erythroid induction agents, with compounds 1, 2, and 3 being particularly effective inducers of HbF expression. Additionally, these compounds exhibited non-cytotoxic effects on the 3T3 cell line, indicating their potential for further development as fetal hemoglobin inducers for the treatment of beta-hemoglobinopathies.
MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Cristina Zuccato, Lucia Carmela Cosenza, Matteo Zurlo, Ilaria Lampronti, Monica Borgatti, Chiara Scapoli, Roberto Gambari, Alessia Finotti
Summary: This study analyzed Cinchona alkaloids as natural HbF-inducing agents in human erythroid cells, and found that cinchonidine and quinidine are potent inducers of gamma-globin mRNA and HbF in erythroid progenitor cells isolated from beta-thalassemia patients. These compounds may be considered for the development of pre-clinical approaches for therapeutic protocols of beta-thalassemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Sukanya Chumchuen, Orapan Sripichai, Natee Jearawiriyapaisarn, Suthat Fucharoen, Chayanon Peerapittayamongkol, Michela Grosso
Summary: Imbalanced globin chain output is important in thalassemia pathophysiology. Induction of fetal hemoglobin through targeting HBS1L shows promising therapeutic potential in beta-thalassemia patients by upregulating gamma-globin mRNA and increasing the percentage of fetal hemoglobin.
Article
Biochemistry & Molecular Biology
Fizza Iftikhar, Muhammad Behroz Naeem Khan, Syeda Tehreem, Nayab Kanwal, Syed Ghulam Musharraf
Summary: Pharmacological induction of fetal hemoglobin has potential therapeutic benefits for ss-hemoglobinopathies, and Fagonia indica has been identified as a relevant treatment option for ss-thalassemia. The compound 8 from F. indica has demonstrated strong HbF induction ability in vitro and in vivo. Treatment with compound 8 led to erythroid differentiation, increased cellular proliferation, enhanced accumulation of total hemoglobin, and upregulation of y-globin gene expression. These findings suggest that compound 8 could be a promising HbF-inducing agent for ss-thalassemia, warranting further preclinical and clinical studies.
BIOORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Abhirup Bagchi, Nivedhitha Devaraju, Karthik Chambayil, Vignesh Rajendiran, Vigneshwaran Venkatesan, Nilofer Sayed, Aswin Anand Pai, Aneesha Nath, Ernest David, Yukio Nakamura, Poonkuzhali Balasubramanian, Alok Srivastava, Saravanabhavan Thangavel, Kumarasamypet M. Mohankumar, Shaji R. Velayudhan
Summary: This study presents novel lineage-specific lentiviral RNAi vectors that efficiently reduce target gene expression in erythroid cells, making them suitable for gene therapy of hemoglobinopathies and high-throughput RNAi screening for studying normal and pathological erythropoiesis.
SCIENTIFIC REPORTS
(2022)
Review
Virology
Christopher Perry, Andrea C. M. E. Rayat
Summary: This comprehensive review discusses the importance of individual bioprocess operations in lentiviral vector (LV) production, emphasizing the role of envelope proteins and bioprocessing on LVs. It explores considerations for optimization and scalability during production, as well as key steps such as purification and quantification of LVs.
Article
Genetics & Heredity
Lucia Carmela Cosenza, Cristina Zuccato, Matteo Zurlo, Roberto Gambari, Alessia Finotti
Summary: Gene editing is an effective strategy for correcting genetic mutations in monogenic hereditary diseases, and combining it with HbF induction protocols can achieve de novo production of HbA and an increase in induced HbF.
Article
Multidisciplinary Sciences
Janet L. Kwiatkowski
Summary: This review discusses several treatment options for individuals with transfusion-dependent beta thalassemia, including allogeneic hematopoietic stem cell transplantation and gene addition therapy. The efficacy and safety data from several clinical trials are mentioned.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Sophie Ramadier, Anne Chalumeau, Tristan Felix, Nadia Othman, Sherazade Aknoun, Antonio Casini, Giulia Maule, Cecile Masson, Anne De Cian, Giacomo Frati, Megane Brusson, Jean-Paul Concordet, Marina Cavazzana, Anna Cereseto, Wassim El Nemer, Mario Amendola, Benoit Wattellier, Vasco Meneghini, Annarita Miccio
Summary: In this study, a novel therapeutic approach combining LV-based gene addition and CRISPR-Cas9 strategies was developed to treat Sickle Cell Disease. This versatile platform reduced the expression of sickle beta-globin and increased the expression of anti-sickling globins, resulting in improved treatment efficacy.
Article
Immunology
Maria Carmina Castiello, Martina Di Verniere, Elena Draghici, Elena Fontana, Sara Penna, Lucia Sereni, Alessandra Zecchillo, Denise Minuta, Paolo Uva, Marco Zahn, Irene Gil-Farina, Andrea Annoni, Silvia Iaia, Lisa M. Ott de Bruin, Luigi D. Notarangelo, Karin Pike-Overzet, Frank J. T. Staal, Anna Villa, Valentina Capo
Summary: This study evaluated the efficacy of gene therapy in hypomorphic RAG1 mouse models and found that it has the potential to partially alleviate the immune deficiency in these patients. However, further research is needed before commencing RAG gene therapy in these highly complex patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Nudrat Aziz, Muhammad Noman Khan, Faraz Ul Haq, Fayaz Ahmed, Arslan Ali, Hesham R. El-Seedi, Syed Ghulam Musharraf
Summary: This study explores the potential of Aquilegia fragrans and Aquilegia pubiflora methanolic extracts in inducing fetal hemoglobin activity in K562 cell line, suggesting their potential in treating beta-thalassemia. Thirty compounds were identified in both species using high-resolution mass spectrometry techniques, with statistical analyses performed to evaluate compound distribution. The chemical fingerprints established in this research will aid in the standardization and quality control of plant extracts.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2021)
Review
Pharmacology & Pharmacy
Parin Rattananon, Usanarat Anurathapan, Kanit Bhukhai, Suradej Hongeng
Summary: Beta-thalassemia is a disease caused by defects in beta-globin synthesis, commonly treated with blood transfusions which can lead to chronic iron overload; transplantation of healthy hematopoietic stem cells is considered an alternative, but carries certain risks.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Chemistry, Analytical
Ruina Shi, Shenghua Jia, Huwei Liu, Honggang Nie
Summary: This review summarizes the latest technologies and enhancements used in large-scale purification of lentiviral vectors, aiming to address the issues of insufficient yield and recovery rate.
JOURNAL OF SEPARATION SCIENCE
(2022)
Article
Hematology
Alessio Cantore, Luigi Naldini
Summary: The development of new treatments for haemophilia has progressed rapidly in the past decade, with gene therapy offering the potential for lifelong treatment. Recombinant adeno-associated virus vectors have shown good efficacy and safety in liver-directed gene therapy, but have limitations. HIV-derived lentiviral vectors integrate into target cell chromatin and are maintained during cell duplication, potentially providing long-term expression advantages especially in pediatric patients.
Article
Virology
Nicole Cordes, Nora Winter, Carolin Kolbe, Bettina Kotter, Joerg Mittelstaet, Mario Assenmacher, Toni Cathomen, Andrew Kaiser, Thomas Schaser
Summary: This study reports the development of a versatile targeting system for MV-LVs, which enables selective gene transfer by mixing with biotinylated adapter molecules. The system demonstrates high efficiency and flexibility, making it suitable for improving the safety and efficacy of cellular therapies.
Article
Cell Biology
Simone Patergnani, Antonino Giattino, Nicoletta Bianchi, Carlotta Giorgi, Paolo Pinton, Gianluca Aguiari
Summary: This study reveals that inhibition of mTOR activates autophagy in ADPKD cells, leading to drug degradation through autophagic vesicles and reduced therapeutic efficacy. The combination of mTOR inhibitor and autophagy inhibitor enhances the decrease in cell proliferation caused by mTOR inhibition. Targeting MDM2, a downstream effector of mTOR signaling, prevents TP53 degradation and induces cell apoptosis, providing a new therapeutic option for ADPKD treatment.
BIOLOGY OF THE CELL
(2023)
Article
Biochemistry & Molecular Biology
Riccardo Barbari, Chiara Tupini, Elisa Durini, Eleonora Gallerani, Francesco Nicoli, Ilaria Lampronti, Anna Baldisserotto, Stefano Manfredini
Summary: A current research trend in the health field is to discover multifunctional compounds that can interact with multiple biological targets, simplifying multidrug therapies and improving patient compliance. This study synthesized new chemicals with a benzothiazole structure and tested them for antioxidant, UV-filtering, and antitumor activities. Compound BZTcin4 showed excellent activity and selectivity towards Colo-38, with good antioxidant capacity and broad-spectrum photoprotective profile.
Article
Multidisciplinary Sciences
Valentino Bezzerri, Valentina Gentili, Martina Api, Alessia Finotti, Chiara Papi, Anna Tamanini, Christian Boni, Elena Baldisseri, Debora Olioso, Martina Duca, Erika Tedesco, Sara Leo, Monica Borgatti, Sonia Volpi, Paolo Pinton, Giulio Cabrini, Roberto Gambari, Francesco Blasi, Giuseppe Lippi, Alessandro Rimessi, Roberta Rizzo, Marco Cipolli
Summary: As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis could be considered a comorbidity for coronavirus disease 2019. However, current clinical evidence suggests that cystic fibrosis may actually protect against SARS-CoV-2 infection. The expression of SARS-CoV-2 receptors in primary airway epithelial cells is regulated by the CFTR channel, and dysfunctional CFTR channels in cystic fibrosis cells result in reduced viral entry and replication.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Carla M. P. Ribeiro, Matthew G. Higgs, Marianne S. Muhlebach, Matthew C. Wolfgang, Monica Borgatti, Ilaria Lampronti, Giulio Cabrini
Summary: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have provided a significant therapeutic advantage for people with cystic fibrosis (pwCF). However, these modulators face limitations in reducing chronic lung bacterial infection and inflammation, which are the main causes of respiratory damage and insufficiency in pwCF, especially in adults. This article revisits the debated issues of pulmonary bacterial infection and inflammatory processes in pwCF, highlighting the mechanisms favoring bacterial infection, the interplay between Pseudomonas aeruginosa and Staphylococcus aureus, and the cross-talk among bacteria, bronchial epithelial cells, and host immune defenses. The recent findings on the effect of CFTR modulators on bacterial infection and inflammation are also presented to identify potential therapeutic targets for respiratory pathology in pwCF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Chiara Tupini, Matteo Zurlo, Jessica Gasparello, Irene Lodi, Alessia Finotti, Thomas Scattolin, Fabiano Visentin, Roberto Gambari, Ilaria Lampronti
Summary: This study demonstrates that the combination therapy using PNA targeting miR-221 and a new palladium allyl complex is effective in inducing apoptosis in tumor cells. Therefore, this combination treatment could be a promising approach for cancer control.
Article
Biochemistry & Molecular Biology
Anna Baldisserotto, Riccardo Barbari, Chiara Tupini, Raissa Buzzi, Elisa Durini, Ilaria Lampronti, Stefano Manfredini, Erika Baldini, Silvia Vertuani
Summary: This research explored the use of plant extracts as potential new active ingredients in nutrition, cosmetics, and pharmaceuticals. The study focused on Moringa oleifera, a plant known for its nutritional properties, and evaluated the antioxidant, antifungal, photoprotective, and cytotoxicity effects of different extracts and infusions obtained from leaves harvested in Paraguay. The results suggest that Moringa oleifera could be beneficial in combating skin aging and oxidative stress, and may have potential applications as natural additives in sunscreens.
Article
Biology
Francesca Crudele, Nicoletta Bianchi, Anna Terrazzan, Pietro Ancona, Antonio Frassoldati, Paolo Gasparini, Adamo P. D'Adamo, Dimitrios Papaioannou, Ramiro Garzon, Anna Wojcicka, Pawel Gaj, Krystian Jazdzewski, Jeffrey Palatini, Stefano Volinia
Summary: In this study, we investigated the function of human genes encoding circular RNAs (circRNAs), which are still a topic of debate. We identified 183 genes that encode circRNAs and found that they are differentially expressed in cancer tissues, suggesting a potential role in cancer. These circRNAs may contribute to cellular and systemic processes by generating novel proteins.
Article
Biochemistry & Molecular Biology
Anna Terrazzan, Francesca Crudele, Fabio Corra, Pietro Ancona, Jeffrey Palatini, Nicoletta Bianchi, Stefano Volinia
Summary: We investigated the dysregulation of circRNAs and their linRNAs in breast cancer cell lines under various drug treatments. The expression ratios of circRNA/linRNA increased due to the downregulation of linRNA and upregulation of circRNA within the same gene. Different drugs had different effects on the regulation of circRNAs and linRNAs, some of which were associated with cancer progression and drug resistance.
Article
Biochemistry & Molecular Biology
Eric W. J. Gates, Nicholas D. Calvert, Nicholas J. Cundy, Federica Brugnoli, Pauline Navals, Alexia Kirby, Nicoletta Bianchi, Gautam Adhikary, Adam J. Shuhendler, Richard L. Eckert, Jeffrey W. Keillor
Summary: TG2 is a multifunctional enzyme involved in protein crosslinking and intracellular signaling. It is implicated in various diseases, including celiac disease, fibrosis, and cancer. The development of novel TG2 inhibitors that selectively target extracellular TG2 is important for therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Laura Breda, Tyler E. Papp, Michael P. Triebwasser, Amir Yadegari, Megan T. Fedorky, Naoto Tanaka, Osheiza Abdulmalik, Giulia Pavani, Yongping Wang, Stephan A. Grupp, Stella T. Chou, Houping Ni, Barbara L. Mui, Ying K. Tam, Drew Weissman, Stefano Rivella, Hamideh Parhiz
Summary: This study developed a nanoparticle system that can target hematopoietic stem cells in vivo and achieved correction of diseased cells through mRNA delivery. Furthermore, this system enables non-genotoxic conditioning for stem cells, providing a new approach for HSCT.
Article
Genetics & Heredity
Alessia Finotti, Jessica Gasparello, Cristina Zuccato, Lucia Carmela Cosenza, Enrica Fabbri, Nicoletta Bianchi, Roberto Gambari
Summary: The anticancer drug mithramycin (MTH) has been found to induce the production of fetal hemoglobin (HbF) in erythroid precursor cells, which has clinical significance in treating β-thalassemia and improving sickle-cell disease. This study identifies the down-regulation of the BCL11A gene transcription and the inhibition of its molecular interactions with the gamma-globin gene promoter as the mechanisms of action for MTH.
Review
Biology
Roberto Gambari, Cristina Zuccato, Lucia Carmela Cosenza, Matteo Zurlo, Jessica Gasparello, Alessia Finotti, Maria Rita Gamberini, Marco Prosdocimi
Summary: This review article presents the fascinating story of sirolimus (rapamycin), a drug known to induce fetal hemoglobin and of great interest for the treatment of beta-thalassemia. It discusses the discovery of rapamycin, its antimicrobial properties, its inhibition of tumor cell growth, and its potential immunosuppressive effects. The article also highlights recent findings regarding rapamycin's ability to induce fetal hemoglobin, paving the way for clinical trials on beta-thalassemia patients.
Article
Biochemistry & Molecular Biology
Cristina Zuccato, Lucia Carmela Cosenza, Matteo Zurlo, Giulia Breveglieri, Nicoletta Bianchi, Ilaria Lampronti, Jessica Gasparello, Chiara Scapoli, Monica Borgatti, Alessia Finotti, Roberto Gambari
Summary: The human homologue of mouse Ly-1 antibody reactive clone protein (LYAR) is a potential regulator of gamma-globin gene transcription. The LYAR rs368698783 (G > A) polymorphism is present in beta-thalassemia patients and reduces the LYAR binding efficiency to the A gamma-globin gene. This study aimed to stratify beta-thalassemia patients based on the rs368698783 (G > A) polymorphism and investigate their erythroid precursor cells' response to selected HbF inducers in vitro.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)