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  1. AU="Giacomo Frati"
  2. AU=Kokhaei P
  3. AU="Charikleia Triantopoulou"
  4. AU="Salil Bhargava"
  5. AU="Jong-Eun Lee"
  6. AU="Vargas C, Laura"

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  1. Artikel ; Online: Genome Editing for β-Hemoglobinopathies

    Giacomo Frati / Annarita Miccio

    Journal of Clinical Medicine, Vol 10, Iss 3, p

    Advances and Challenges

    2021  Band 482

    Abstract: β-hemoglobinopathies are the most common genetic disorders worldwide and are caused by mutations affecting the production or the structure of adult hemoglobin. Patients affected by these diseases suffer from anemia, impaired oxygen delivery to tissues, ... ...

    Abstract β-hemoglobinopathies are the most common genetic disorders worldwide and are caused by mutations affecting the production or the structure of adult hemoglobin. Patients affected by these diseases suffer from anemia, impaired oxygen delivery to tissues, and multi-organ damage. In the absence of a compatible donor for allogeneic bone marrow transplantation, the lifelong therapeutic options are symptomatic care, red blood cell transfusions and pharmacological treatments. The last decades of research established lentiviral-mediated gene therapy as an efficacious therapeutic strategy. However, this approach is highly expensive and associated with a variable outcome depending on the effectiveness of the viral vector and the quality of the cell product. In the last years, genome editing emerged as a valuable tool for the development of curative strategies for β-hemoglobinopathies. Moreover, due to the wide range of its applications, genome editing has been extensively used to study regulatory mechanisms underlying globin gene regulation allowing the identification of novel genetic and pharmacological targets. In this work, we review the current advances and challenges of genome editing approaches to β-hemoglobinopathies. Special focus has been directed towards strategies aimed at correcting the defective β-globin gene or at inducing fetal hemoglobin (HbF), which are in an advanced state of clinical development.
    Schlagwörter genome editing ; β-hemoglobinopathies ; gene therapy ; Medicine ; R
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2021-01-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: MicroRNAs in Coronary Heart Disease

    Elena Cavarretta / Giacomo Frati

    BioMed Research International, Vol

    Ready to Enter the Clinical Arena?

    2016  Band 2016

    Abstract: Coronary artery disease (CAD) and its complication remain the leading cause of mortality in industrialized countries despite great advances in terms of diagnosis, prognosis, and treatment options. MicroRNAs (miRNAs), small noncoding RNAs, act as ... ...

    Abstract Coronary artery disease (CAD) and its complication remain the leading cause of mortality in industrialized countries despite great advances in terms of diagnosis, prognosis, and treatment options. MicroRNAs (miRNAs), small noncoding RNAs, act as posttranscriptional gene expression modulators and have been implicated as key regulators in several physiological and pathological processes linked to CAD. Circulating miRNAs have been evaluated as promising novel biomarkers of CAD, acute coronary syndromes, and acute myocardial infarction, with prognostic implications. Several challenges related to technical aspects, miRNAs normalization, drugs interaction, and quality reporting of statistical multivariable analysis of the miRNAs observational studies remain unresolved. MicroRNA-based therapies in cardiovascular diseases are not ready yet for human trials but definitely appealing. Through this review we will provide clinicians with a concise overview of the pros and cons of microRNAs.
    Schlagwörter Medicine ; R
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2016-01-01T00:00:00Z
    Verlag Hindawi Publishing Corporation
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart

    Valeria Taliani / Giulia Buonaiuto / Fabio Desideri / Adriano Setti / Tiziana Santini / Silvia Galfrè / Leonardo Schirone / Davide Mariani / Giacomo Frati / Valentina Valenti / Sebastiano Sciarretta / Emerald Perlas / Carmine Nicoletti / Antonio Musarò / Monica Ballarino

    eLife, Vol

    2023  Band 12

    Abstract: Long noncoding RNAs (lncRNAs) are emerging as critical regulators of heart physiology and disease, although the studies unveiling their modes of action are still limited to few examples. We recently identified pCharme, a chromatin-associated lncRNA whose ...

    Abstract Long noncoding RNAs (lncRNAs) are emerging as critical regulators of heart physiology and disease, although the studies unveiling their modes of action are still limited to few examples. We recently identified pCharme, a chromatin-associated lncRNA whose functional knockout in mice results in defective myogenesis and morphological remodeling of the cardiac muscle. Here, we combined Cap-Analysis of Gene Expression (CAGE), single-cell (sc)RNA sequencing, and whole-mount in situ hybridization analyses to study pCharme cardiac expression. Since the early steps of cardiomyogenesis, we found the lncRNA being specifically restricted to cardiomyocytes, where it assists the formation of specific nuclear condensates containing MATR3, as well as important RNAs for cardiac development. In line with the functional significance of these activities, pCharme ablation in mice results in a delayed maturation of cardiomyocytes, which ultimately leads to morphological alterations of the ventricular myocardium. Since congenital anomalies in myocardium are clinically relevant in humans and predispose patients to major complications, the identification of novel genes controlling cardiac morphology becomes crucial. Our study offers unique insights into a novel lncRNA-mediated regulatory mechanism promoting cardiomyocyte maturation and bears relevance to Charme locus for future theranostic applications.
    Schlagwörter ncRNA ; lncRNA ; cardiomyogenesis ; heart ; muscle ; development ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2023-03-01T00:00:00Z
    Verlag eLife Sciences Publications Ltd
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Inflammatory status in pediatric sickle cell disease

    Silvio Marchesani / Valentina Bertaina / Olivia Marini / Matilde Cossutta / Margherita Di Mauro / Gioacchino Andrea Rotulo / Paolo Palma / Letizia Sabatini / Maria Isabella Petrone / Giacomo Frati / Giulia Monteleone / Giuseppe Palumbo / Giulia Ceglie

    Frontiers in Molecular Biosciences, Vol

    Unravelling the role of immune cell subsets

    2023  Band 9

    Abstract: Introduction: The mutation of the beta-globin gene that causes sickle cell disease (SCD) results in pleiotropic effects, such as hemolysis and vaso-occlusive crisis that can induce inflammatory mechanisms with deleterious consequences on the organism. ... ...

    Abstract Introduction: The mutation of the beta-globin gene that causes sickle cell disease (SCD) results in pleiotropic effects, such as hemolysis and vaso-occlusive crisis that can induce inflammatory mechanisms with deleterious consequences on the organism. Moreover, SCD patients display an increased susceptibility to infections. Few studies are currently available that evaluate a wide immunological profile in a pediatric population. This study proposes an evaluation of the immune profile in subjects with SCD in a pediatric population through a detailed analysis by flow cytometry.Methods and Materials: Peripheral blood samples from 53 pediatric patients with SCD (mean age 9.8 years, interquartile range 9 years) were obtained and then analyzed by flow cytometry, in order to evaluate changes in the immune populations compared to 40 healthy donors (mean age 7.3 years, interquartile range 9.5 years).Results: Our data showed an increase in neutrophils (with a reduction in the CD62L + subpopulation) and monocytes (with a decrease in HLA-DRlow monocytes) with normal values of lymphocytes in SCD patients. In the lymphocyte subpopulations analysis we observed lower values of CD4+ T cells (with higher number of memory and central memory T lymphocytes) with increased frequency of CD8+ T cells (with a predominant naive pattern). Moreover, we observed higher values of CD39+ Tregs and lower HLA-DR+ and CD39− T cells with an increased Th17, Th1-17 and Th2 response.Conclusion: We observed immunological alterations typical of an inflammatory status (increase in activated neutrophils and monocytes) associated with a peculiar Treg pattern (probably linked to a body attempt to minimize inflammation intrinsic to SCD). Furthermore, we highlighted a T helper pathway associated with inflammation in line with other studies. Our data showed that immunological markers may have an important role in the understanding the pathophysiology of SCD and in optimizing targeted therapeutic strategies for each patient.
    Schlagwörter sickle cell disease ; immune system ; immunophenotype ; anemia ; hemoglobinopathies ; flow cytofluorimetry ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2023-01-01T00:00:00Z
    Verlag Frontiers Media S.A.
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Remodeled eX vivo muscle engineered tissue improves heart function after chronic myocardial ischemia

    Marianna Cosentino / Carmine Nicoletti / Valentina Valenti / Leonardo Schirone / Flavio Di Nonno / Ludovica Apa / Mariam Zouhair / Desiree Genovese / Luca Madaro / Simone Dinarelli / Marco Rossi / Zaccaria Del Prete / Sebastiano Sciarretta / Giacomo Frati / Emanuele Rizzuto / Antonio Musarò

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Band 15

    Abstract: Abstract The adult heart displays poor reparative capacities after injury. Cell transplantation and tissue engineering approaches have emerged as possible therapeutic options. Several stem cell populations have been largely used to treat the infarcted ... ...

    Abstract Abstract The adult heart displays poor reparative capacities after injury. Cell transplantation and tissue engineering approaches have emerged as possible therapeutic options. Several stem cell populations have been largely used to treat the infarcted myocardium. Nevertheless, transplanted cells displayed limited ability to establish functional connections with the host cardiomyocytes. In this study, we provide a new experimental tool, named 3D eX vivo muscle engineered tissue (X-MET), to define the contribution of mechanical stimuli in triggering functional remodeling and to rescue cardiac ischemia. We revealed that mechanical stimuli trigger a functional remodeling of the 3D skeletal muscle system toward a cardiac muscle-like structure. This was supported by molecular and functional analyses, demonstrating that remodeled X-MET expresses relevant markers of functional cardiomyocytes, compared to unstimulated and to 2D- skeletal muscle culture system. Interestingly, transplanted remodeled X-MET preserved heart function in a murine model of chronic myocardial ischemia and increased survival of transplanted injured mice. X-MET implantation resulted in repression of pro-inflammatory cytokines, induction of anti-inflammatory cytokines, and reduction in collagen deposition. Altogether, our findings indicate that biomechanical stimulation induced a cardiac functional remodeling of X-MET, which showed promising seminal results as a therapeutic product for the development of novel strategies for regenerative medicine.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2023-06-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Mitochondria and Doxorubicin-Induced Cardiomyopathy

    Leonardo Schirone / Luca D’Ambrosio / Maurizio Forte / Riccardo Genovese / Sonia Schiavon / Giulia Spinosa / Giuliano Iacovone / Valentina Valenti / Giacomo Frati / Sebastiano Sciarretta

    Cells, Vol 11, Iss 2000, p

    A Complex Interplay

    2022  Band 2000

    Abstract: Cardiotoxicity has emerged as a major side effect of doxorubicin (DOX) treatment, affecting nearly 30% of patients within 5 years after chemotherapy. Heart failure is the first non-cancer cause of death in DOX-treated patients. Although many different ... ...

    Abstract Cardiotoxicity has emerged as a major side effect of doxorubicin (DOX) treatment, affecting nearly 30% of patients within 5 years after chemotherapy. Heart failure is the first non-cancer cause of death in DOX-treated patients. Although many different molecular mechanisms explaining the cardiac derangements induced by DOX were identified in past decades, the translation to clinical practice has remained elusive to date. This review examines the current understanding of DOX-induced cardiomyopathy (DCM) with a focus on mitochondria, which were increasingly proven to be crucial determinants of DOX-induced cytotoxicity. We discuss DCM pathophysiology and epidemiology and DOX-induced detrimental effects on mitochondrial function, dynamics, biogenesis, and autophagy. Lastly, we review the current perspectives to contrast the development of DCM, which is still a relatively diffused, invalidating, and life-threatening condition for cancer survivors.
    Schlagwörter DOX ; anthracycline ; cardiomyopathy ; mitochondria ; heart ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2022-06-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: An Overview of the Molecular Mechanisms Associated with Myocardial Ischemic Injury

    Leonardo Schirone / Maurizio Forte / Luca D’Ambrosio / Valentina Valenti / Daniele Vecchio / Sonia Schiavon / Giulia Spinosa / Gianmarco Sarto / Vincenzo Petrozza / Giacomo Frati / Sebastiano Sciarretta

    Cells, Vol 11, Iss 1165, p

    State of the Art and Translational Perspectives

    2022  Band 1165

    Abstract: Cardiovascular disease is the leading cause of death in western countries. Among cardiovascular diseases, myocardial infarction represents a life-threatening condition predisposing to the development of heart failure. In recent decades, much effort has ... ...

    Abstract Cardiovascular disease is the leading cause of death in western countries. Among cardiovascular diseases, myocardial infarction represents a life-threatening condition predisposing to the development of heart failure. In recent decades, much effort has been invested in studying the molecular mechanisms underlying the development and progression of ischemia/reperfusion (I/R) injury and post-ischemic cardiac remodeling. These mechanisms include metabolic alterations, ROS overproduction, inflammation, autophagy deregulation and mitochondrial dysfunction. This review article discusses the most recent evidence regarding the molecular basis of myocardial ischemic injury and the new potential therapeutic interventions for boosting cardioprotection and attenuating cardiac remodeling.
    Schlagwörter ischemic injury ; myocardial ischemia ; infarction ; ischemia/reperfusion (I/R) ; molecular ; mechanisms ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2022-03-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Cell Clearing Systems as Targets of Polyphenols in Viral Infections

    Fiona Limanaqi / Carla Letizia Busceti / Francesca Biagioni / Gloria Lazzeri / Maurizio Forte / Sonia Schiavon / Sebastiano Sciarretta / Giacomo Frati / Francesco Fornai

    Antioxidants, Vol 9, Iss 1105, p

    Potential Implications for COVID-19 Pathogenesis

    2020  Band 1105

    Abstract: The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated the ongoing coronavirus disease-2019 (COVID-19) pandemic, still with an uncertain outcome. Besides pneumonia and acute lung injury (ALI) or acute ... ...

    Abstract The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated the ongoing coronavirus disease-2019 (COVID-19) pandemic, still with an uncertain outcome. Besides pneumonia and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), other features became evident in the context of COVID-19. These includes endothelial and coagulation dysfunction with disseminated intravascular coagulation (DIC), and multiple organ dysfunction syndrome (MODS), along with the occurrence of neurological alterations. The multi-system nature of such viral infection is a witness to the exploitation and impairment of ubiquitous subcellular and metabolic pathways for the sake of its life-cycle, ranging from host cell invasion, replication, transmission, up to a cytopathic effect and overt systemic inflammation. In this frame, alterations in cell-clearing systems of the host are emerging as a hallmark in the pathogenesis of various respiratory viruses, including SARS-CoV-2. Indeed, exploitation of the autophagy and proteasome pathways might contribute not only to the replication of the virus at the site of infection but also to the spreading of either mature virions or inflammatory mediators at both cellular and multisystem levels. In this frame, besides a pharmacological therapy, many researchers are wondering if some non-pharmacological substances might counteract or positively modulate the course of the infection. The pharmacological properties of natural compounds have gained increasing attention in the field of alternative and adjunct therapeutic approaches to several diseases. In particular, several naturally-occurring herbal compounds (mostly polyphenols) are reported to produce widespread antiviral, anti-inflammatory, and anti-oxidant effects while acting as autophagy and (immuno)-proteasome modulators. This article attempts to bridge the perturbation of autophagy and proteasome pathways with the potentially beneficial effects of specific phytochemicals and flavonoids in viral infections, with a focus on the multisystem SARS-CoV-2 infection.
    Schlagwörter autophagy ; immunoproteasome ; coronavirus ; inflammation ; resveratrol ; quercetin ; Therapeutics. Pharmacology ; RM1-950 ; covid19
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2020-11-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: Impact of Electronic Alternatives to Tobacco Cigarettes on Indoor Air Particular Matter Levels

    Carmela Protano / Maurizio Manigrasso / Vittoria Cammalleri / Giuseppe Biondi Zoccai / Giacomo Frati / Pasquale Avino / Matteo Vitali

    International Journal of Environmental Research and Public Health, Vol 17, Iss 2947, p

    2020  Band 2947

    Abstract: An aerosol study was carried out in a test room measuring particulate matter (PM) with an aerodynamic diameter smaller than 10, 4, 2.5 and 1 µm (PM 10 , PM 4 , PM 2.5 , PM 1 ) before and during the use of electronic alternatives to tobacco cigarettes ( ... ...

    Abstract An aerosol study was carried out in a test room measuring particulate matter (PM) with an aerodynamic diameter smaller than 10, 4, 2.5 and 1 µm (PM 10 , PM 4 , PM 2.5 , PM 1 ) before and during the use of electronic alternatives to tobacco cigarettes (EATC) IQOS ® , GLO ® , JUUL ® , with different kinds of sticks/pods, as well as during the smoking of a conventional tobacco cigarette. The aerosol was mainly in the PM 1 size range (>95%). All studied EATCs caused lower indoor PM 1 concentrations than conventional tobacco cigarettes. Nevertheless, they determined a worsening of indoor-PM 1 concentration that ranged from very mild for JUUL ® —depending on the pod used—to considerably severe for IQOS ® and GLO ® . Median values ranged from 11.00 (Iqos3 and Juul2) to 337.5 µg m −3 (Iqos4). The high variability of particle loadings was attributed both to the type of stick/pod used and to the different way of smoking of volunteers who smoked/vaped during the experiments. Moreover, during vaping IQOS ® and GLO ® indoor PM 1 concentrations reach levels by far higher than outdoor concentrations that range from 14 to 21 µg m −3 , especially during the exhalation of the smoke. From these results emerge an urgent need of a legislative regulation limiting the use of such devices in public places.
    Schlagwörter indoor air ; particulate matter ; electronic cigarettes ; heat-not-burn products ; IQOS ® ; GLO ® ; Medicine ; R
    Thema/Rubrik (Code) 333 ; 290
    Sprache Englisch
    Erscheinungsdatum 2020-04-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel: The Positive Effects of Exercise in Chemotherapy-Related Cardiomyopathy.

    Elena, Cavarretta / Giorgio, Mastroiacovo / Annik, Lupieri / Giacomo, Frati / Mariangela, Peruzzi

    Advances in experimental medicine and biology

    2017  Band 1000, Seite(n) 103–129

    Abstract: Anthracyclines such as doxorubicin, daunorubicin, epirubicin, mitoxantrone and idarubicin, are powerful chemotherapeutic drugs used both in children and adult populations. Their properties made them particularly suitable for a large variety of neoplasms ... ...

    Abstract Anthracyclines such as doxorubicin, daunorubicin, epirubicin, mitoxantrone and idarubicin, are powerful chemotherapeutic drugs used both in children and adult populations. Their properties made them particularly suitable for a large variety of neoplasms including breast adenocarcinoma, small cell lung cancer and acute leukemia. Early and late anthracycline-induced cardiotoxicity is a well-known phenomenon, and the incidence of heart failure in patients receiving doxorubicin is 2.2%, with a mortality rate over 60% at 2 years. Prognosis can be improved by prevention, early detection and treatment. A specific treatment for anthracycline-induced cardiotoxicity is not yet available, but non-pharmacological measures such as exercise, lifestyle changes and control of risk factors have shown a cardioprotective effect. Exercise training represents a viable non-pharmacological treatment as it increases cardiovascular reserve and endothelial function, regulates proapoptotic signaling, protects against reactive oxygen species (ROS), and decreases autophagy/lysosomal signaling. However, no current guidelines are available for prevention management in cancer patients. Pharmacological measures both for prevention and treatment are those used for heart failure (β-blockers, angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors, statins, dexrazoxane and aldosteron antagonists). In this chapter, we will discuss how the evaluation, monitoring and prevention of chemotherapy-related cardiomyopathy is correlated with physical exercise.
    Sprache Englisch
    Erscheinungsdatum 2017
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-981-10-4304-8_8
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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