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Facing ethical concerns in the age of precise gene therapy:Outlook on inherited arrhythmias

World Journal of Cardiology 2024年第2期16卷 64-66页

作者： federico carbone Fabrizio Montecucco Department of Internal Medicine University of GenoaGenoa 16132Italy IRCCS Ospedale Policlinico San Martino Genoa Italian Cardiovascular NetworkGenoa 16132Italy

This editorial,comments on the article by Spartalis et al published in the recent issue of the World Journal of Cardiology.We here provide an outlook on potential ethical concerns related to the future application of gene therapy in the field of inherited arrhythmias.As monogenic diseases with no or few therapeutic options available through standard care,inherited arrhythmias are ideal candidates to gene therapy in their treatment.Patients with inherited arrhythmias typically have a poor quality of life,especially young people engaged in agonistic sports.While genome editing for treatment of inherited arrhythmias still has theoretical application,advances in CRISPR/Cas9 technology now allows the generation of knock-in animal models of the disease.However,clinical translation is somehow expected soon and this make consistent discussing about ethical concerns related to gene editing in inherited arrhythmias.Genomic off-target activity is a known technical issue,but its relationship with ethnical and individual genetical diversity raises concerns about an equitable accessibility.Meanwhile,the costeffectiveness may further limit an equal distribution of gene therapies.The economic burden of gene therapies on healthcare systems is is increasingly recognized as a pressing concern.A growing body of studies are reporting uncertainty in payback periods with intuitive short-term effects for insurance-based healthcare systems,but potential concerns for universal healthcare systems in the long term as well.Altogether,those aspects strongly indicate a need of regulatory entities to manage those issues.

关键词： Ethics Inherited arrhythmias CRISPR/Cas9 Gene therapy Equitable accessibility

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Ultrasound unveiling:Decoding venous congestion in heart failure for precision management of fluid status

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World Journal of Cardiology 2024年第6期16卷 306-309页

作者： Davide Ramoni federico carbone Fabrizio Montecucco Department of Internal Medicine University of GenoaGenoa 16132Italy Department of Internal Medicine IRCCS Ospedale Policlinico San MartinoGenoa 16132Italy

This editorial discusses the manuscript by Di Maria et al,published in the recent issue of the World Journal of Cardiology.We here focus on the still elusive pathophysiological mechanisms underlying cardio-renal syndrome(CRS),despite its high prevalence and the substantial worsening of both kidney function and heart failure.While the measure of right atrial pressure through right cardiac catheterization remains the most accurate albeit invasive and costly procedure,integrating bedside ultrasound into diagnostic protocols may substantially enhance the staging of venous congestion and guide therapeutic decisions.In particular,with the assessment of Doppler patterns across multiple venous districts,the Venous Excess Ultrasound(VExUS)score improves the management of fluid overload and provides insight into the underlying factors contributing to cardio-renal interactions.Integrating specific echocardiographic parameters,particularly those concerning the right heart,may thus improve the VExUS score sensitivity,offering perspective into the nuanced comprehension of cardio-renal dynamics.A multidisciplinary approach that consistently incorporates the use of ultrasound is emerging as a promising advance in the understanding and management of CRS.

关键词： Cardio-renal syndrome Fluid overload Heart failure Ultrasound assessment Venous congestion Venous excess ultrasound score

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Left atrial thrombosis in an anticoagulated patient after bioprosthetic valve replacement:Report of a case

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World Journal of Clinical Cases 2014年第1期2卷 20-23页

作者： Gian Marco Rosa Antonello Parodi Ulrico Dorighi federico carbone Franois Mach Alessandra Quercioli Fabrizio Montecucco Nicolas Vuilleumier Manrico Balbi Claudio Brunelli Clinic of Cardiovascular Diseases Internal Medicine Department San Martino Hospital and University of Genoa 16143 Genoa Italy Division of Cardiology Department of Internal Medicine Foundation for Medical researches University of Geneva 1211 Geneva Switzerland the First Medical Clinic Laboratory of Phagocyte Physiopathology and Inflammation Department of Internal Medicine University of Genoa 16143 Genoa Italy Division of Laboratory Medicine Department of Genetics and Laboratory Medicine Geneva University Hospitals 1211 Geneva Switzerland

We present the case of a 74 year old woman suffering from severe mitral valve incompetence and rapid atrial fibrillation. After an appropriate vitamin K antagonist(VKA) therapy, the patient underwent mitral valve replacement by bioprosthesis. Then, the patient was rehospitalized for jaundice. Suspecting hepatotoxicity, VKA was discontinued and fondaparinux was started. During this treatment, the patient developed a symptomatic atrial thrombus. After exclusion of a hepatic disease, VKA was re-established with hemodynamic and liver enzymes normalization and atrial thrombus resolution. Caution has to be used when considering fondaparinux as an alternative strategy to VKA in patients with multiple thrombotic risk factors.

关键词： Mitral valve Thrombus Prosthetic valve Atrium Hepatotoxicity

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Potential pathophysiological role for the vitamin D deficiency in essential hypertension

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World Journal of Cardiology 2014年第5期6卷 260-276页

作者： federico carbone Fran?ois Mach Nicolas Vuilleumier Fabrizio Montecucco Department of Internal Medicine University of Genoa School of MedicineIRCCS Azienda Ospedaliera Universitaria San MartinoIST Istituto Nazionale per la Ricerca sul Cancro16132 GenoaItaly Cardiology Division Foundation for Medical ResearchesDepartment of Internal MedicineUniversity of Geneva1211 GenevaSwitzerland Division of Laboratory Medicine Department of Genetics and Laboratory MedicineGeneva University Hospitals1205 GenevaSwitzerland

Vitamin D deficiency has been indicated as a pandemicemerging public health problem. In addition to the well-known role on calcium-phosphorus homeostasis in thebone, vitamin D-mediated processes have been recentlyinvestigated on other diseases, such as infections, can-cer and cardiovascular diseases. Recently, both the dis-covery of paracrine actions of vitamin D(recognized as"local vitamin D system") and the link of vitamin D with renin-angiotensin-aldosterone system and the fibroblast growth factor 23/klotho pathways highlighted its ac-tive cardiovascular activity. Focusing on hypertension, this review summarizes the more recent experimental evidence involving the vitamin D system and deficiency in the cardiovascular pathophysiology. In particular, we updated the vascular synthesis/catabolism of vitamin D and its complex interactions between the various endocrine networks involved in the regulation of blood pressure in humans. On the other hand, the conflicting results emerged from the comparison between obser-vational and interventional studies emphasize the frag-mentary nature of our knowledge in the field of vitamin D and hypertension, strongly suggesting the need of further researches in this field.

关键词： Vitamin D Hypertension Cardiovascular disease Renin Angiotensin

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Oxidized organic molecules in the tropical free troposphere over Amazonia

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National Science Review 2024年第1期11卷 174-184页

作者： Qiaozhi Zha Diego Aliaga Radovan Krejci Victoria A.Sinclair Cheng Wu Giancarlo Ciarelli Wiebke Scholz Liine Heikkinen Eva Partoll Yvette Gramlich Wei Huang Markus Leiminger Joonas Enroth Otso Per?kyl? Runlong Cai Xuemeng Chen Alkuin Maximilian Koenig Fernando Velarde Isabel Moreno Tuukka Pet?j? Paulo Artaxo Paolo Laj Armin Hansel Samara carbone Markku Kulmala Marcos Andrade Douglas Worsnop Claudia Mohr federico Bianchi Agrarian Sciences Institute Federal University of Uberl?ndia Beijing Advanced Innovation Center for Soft Matter Science and Engineering Beijing University of Chemical Technology Department of Atmospheric and Oceanic Sciences University of Maryland Aerodyne Research Inc. Department of Environmental System Science ETH Zürich Switzerland and Laboratory of Atmospheric Chemistry Paul Scherrer Institute Institute for Atmospheric and Earth System Research/Physics University of Helsinki Joint International Research Laboratory of Atmospheric and Earth System Sciences Nanjing University Department of Environmental Science & Bolin Centre for Climate Research Stockholm University Department of Chemistry and Molecular Biology University of Gothenburg Institute for Ion and Applied Physics University of Innsbruck Ionicon Analytik GmbH Laboratory for Atmospheric Physics Institute for Physics Research Universidad Mayor de San Andrés Institute of Physics University of Sao Paulo Institute for Geosciences and Environmental Research (IGE) University of Grenoble Alpes

New particle formation(NPF) in the tropical free troposphere(FT) is a globally important source of cloud condensation nuclei, affecting cloud properties and climate. Oxidized organic molecules(OOMs)produced from biogenic volatile organic compounds are believed to contribute to aerosol formation in the tropical FT, but without direct chemical observations. We performed in situ molecular-level OOMs measurements at the Bolivian station Chacaltaya at 5240 m above sea level, on the western edge of Amazonia. For the first time, we demonstrate the presence of OOMs, mainly with 4–5 carbon atoms, in both gas-phase and particle-phase(in terms of mass contribution) measurements in tropical FT air from Amazonia. These observations, combined with air mass history analyses, indicate that the observed OOMs are linked to isoprene emitted from the rainforests hundreds of kilometers away. Based on particle-phase measurements, we find that these compounds can contribute to NPF, at least the growth of newly formed nanoparticles, in the tropical FT on a continental scale. Thus, our study is a fundamental and significant step in understanding the aerosol formation process in the tropical FT.

关键词： oxidized organic molecules tropical aerosol formation Amazon free troposphere

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Cardiac damage in athlete's heart: When the “supernormal” heart fails!

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World Journal of Cardiology 2017年第6期9卷 470-480页

作者： Andreina carbone Antonello D’Andrea Lucia Riegler Raffaella Scarafile Enrica Pezzullo Francesca Martone Raffaella America Biagio Liccardo Maurizio Galderisi Eduardo Bossone Raffaele Calabrò Second University of Naples Monaldi HospitalAORN Ospedali dei Colli Department of Advanced Biomedical Sciences FedericoⅡUniversity Hospital Department of Cardiology and Cardiac Surgery University Hospital San Giovanni di Dio

Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete's blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete's heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded.

关键词：运动员心心脏的损坏纤维变性强烈锻练正确的室的 Arrhythmogenic 发育异常 Atrial 纤维性颤动做 Anabolic-androgenic 类固醇 Hypertrophic 心肌症

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Extracellular proteome of Trichoderma harzianum to identify proteins with biotechnological value

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浙江大学学报（农业与生命科学版） 2004年第4期30卷 452-452页

作者： Ambrosino P Scala V Marra R Vinale F Soriente I Ferraioli S carbone V Ruocco M Woo S L Lorito M Dep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyISA-CNR Avellino ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples Italy

Trichoderma harzianum strain T22 parasitizes and controls many phytopatogenic fungi and is applied commercially as biological control agent. The production of hydrolitic enzymes appears to be a key factor in the parasitic process. We tested the endo-esochitinolitic and glucanolitic activities of culture filtrates of T22 grown under carbon and nitrogen starvation or in presence of biomass or cell walls of the phytopathogenic fungi Botrytis cinerea, Rhizoctonia solani and Pythium ultimum. The highest level of enzimatic activities was found in culture where the mycoparasite interacted with a phytopathogenic fungus. Therefore we used a proteomic approach to investigate changes in the complex mixture of extracellular proteins secreted by T. harzianum strain T22 in order to identify proteins of potential biotechnology value for commercial and industrial use.Proteome technology has greatly enhanced our ability to conduct functional genomics studies. Nevertheless only a few studies have been published so far on the fungal extracellular proteome. Sample preparation remains the most critical step in analyses based on two-dimensional gel electrophoresis (2-DE), and it requires to be optimized for each specific application. In this study, our first aim was to set up the extraction protocol of the extracellular proteins secreted by T . harzianum strain T22 when it was grown in vitro .The secreted proteins were analysed by two-dimensional electrophoresis (2-DE) and substantial changes in the extracellular proteome of the mycoparasite have been observed. Comparing the 2D maps of the fungus grown in minimal medium with glycerol as carbon source (used as control condition) with those obtained in inducing conditions, a lot of novel proteins appeared. The higher number of novel and up-regulated spots was obtained in the presence of Rhizoctonia solani biomass. Other spots were specifically up-regulated by the interaction with different plant pathogens. Differentially expressed proteins were subjected to matrix assisted laser desorpt

关键词：木霉属真菌蛋白质鉴定生物技术植物病原体水解酶

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Proteomic study of three component interactions: plant, pathogens and antagonistic fungi

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浙江大学学报（农业与生命科学版） 2004年第4期30卷 449-449页

作者： Marra R Ambrosino P Scala V Romano C Vinale F Ferraioli S Ruocco M carbone V Woo S L Turrà D Scala F Lorito M Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" Via Università 100 80055 Portici (NA)Italy Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" Via Università 100 80055 Portici (NA)ItalyDip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" Via Università 100 80055 Portici (NA)ItalyDip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" Via Università 100 80055 Portici (NA)ItalyDip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" Via Università 100 80055 Portici (NA)ItalyDip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" Via Università 100 80055 Portici (NA)ItalyDip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" Via Università 100 80055 Portici (NA)Italy ISA-CNR Avellino. Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" Via Università 100 80055 Portici (NA)Italy Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" Via Università 100 80055 Portici (NA)Italy Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" Via Università 100 80055 Portici (NA)Italy Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" Via Università 100 80055 Portici (NA)Italy

The molecular factors involved in the three-way interaction between plant, pathogenic fungi and antagonistic/biocontrol fungi, such as Trichoderma, are still poorly understood, even if they represent a matter of interest for improving crop management and developing new strategies for plant diseases control. The aim of this work is to investigate the components involved in this interaction and, for this purpose, a proteomic approach was used. 2-D maps of the protein extracts from the single components in various interactions between plants (potato, bean, tobacco or tomato), pathogens (Botrytis cinerea, Rhizoctonia solani or Pythium ultimum) and biocontrol fungi (Trichoderma atroviride strain P1 or Trichoderma harzianum strain T22) were obtained. The proteome of each partner was collected separately and extracted by acetone precipitation in presence of trichloroacetic acid and a reducing agent (DTT). The extracted proteins were separated by isoelectrofocusing (IEF), using IPG (Immobilized pH gradient) strips, followed by SDS-PAGE. In order to improve resolution the separations were performed both on wide than narrow pH range and on different gel lengths. Differential spots were noted in the proteome of the three-way interaction when compared to each single component. These were further characterized by mass spectrometry and in silico analysis with the aim of identifying and cloning the relative genes. During the in vitro interaction of T. harzianum strain T22 with tomato and the culture filtrate or cell walls of pathogens, the spot number was higher than in the presence of pathogen biomass. In terms of Trichoderma differential proteins displayed on 2D gels, the most important changes were obtained in the presence of P. ultimum . During the in vivo interaction with tomato, the antagonist proteome changed much more in presence of soilborne fungi R. solani and P. ultimum than with the foliar fungus B. cinerea, both in terms of total and increased or novel spots. In silico analysis of some of those spots revealed homol

关键词：病原体植物拮抗真菌生物防治病害抗性

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