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Mesenchymal stem cell secretome and extracellular vesicles for neurodegenerative diseases: Risk-benefit profile and next steps for the market access

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Bioactive Materials 2023年第11期29卷 16-35页

作者： Lorella Giovannelli Elia Bari Claudio Jommi Fulvio Tartara Daniele Armocida Diego Garbossa fabio Cofano Maria Luisa Torre Lorena Segale Department of Pharmaceutical Sciences University of Piemonte Orientale28100NovaraItaly IRCCS Mondino Foundation 27100PaviaItaly A.U.O Policlinico Umberto INeurosurgery DivisionHuman Neurosciences DepartmentSapienza University00135RomaItaly Department of Neuroscience Rita Levi Montalcini Neurosurgery UnitUniversity of Turin10126TurinItaly PharmaExceed S.r.l 27100PaviaItaly

Neurodegenerative diseases represent a growing burden on healthcare systems worldwide. Mesenchymal stem cells (MSCs) have shown promise as a potential therapy due to their neuroregenerative, neuroprotective, and immunomodulatory properties, which are, however, linked to the bioactive substances they release, collectively known as secretome. This paper provides an overview of the most recent research on the safety and efficacy of MSC-derived secretome and extracellular vesicles (EVs) in clinical (if available) and preclinical models of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington’s disease, acute ischemic stroke, and spinal cord injury. The article explores the biologically active substances within MSC-secretome/EVs, the mechanisms responsible for the observed therapeutic effects, and the strategies that may be used to optimize MSC-secretome/EVs production based on specific therapeutic needs. The review concludes with a critical discussion of current clinical trials and a perspective on potential future directions in translating MSC-secretome and EVs into the clinic, specifically regarding how to address the challenges associated with their pharmaceutical manufacturing, including scalability, batch-to-batch consistency, adherence to Good Manufacturing Practices (GMP) guidelines, formulation, and storage, along with quality controls, access to the market and relative costs, value for money and impact on total expenditure.

关键词： Exosomes Microvesicles Secretome Mesenchymal stem cells Secretome formulation Brain regeneration

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A refined Frequency Domain Decomposition tool for structural modal monitoring in earthquake engineering

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Earthquake Engineering and Engineering Vibration 2017年第3期16卷 627-648页

作者： fabio Pioldi Egidio Rizzi Department of Engineering and Applied Sciences (Dalmine) University of Bergamo viale G. Marconi 5 1-24044 Dalmine (BG) Italy

Output-only structural identification is developed by a refined Frequency Domain Decomposition（rFDD） approach, towards assessing current modal properties of heavy-damped buildings（in terms of identification challenge）, under strong ground motions. Structural responses from earthquake excitations are taken as input signals for the identification algorithm. A new dedicated computational procedure, based on coupled Chebyshev Type Ⅱ bandpass filters, is outlined for the effective estimation of natural frequencies, mode shapes and modal damping ratios. The identification technique is also coupled with a Gabor Wavelet Transform, resulting in an effective and self-contained time-frequency analysis framework. Simulated response signals generated by shear-type frames（with variable structural features） are used as a necessary validation condition. In this context use is made of a complete set of seismic records taken from the FEMA P695 database, i.e. all 44 ＂Far-Field＂（22 NS, 22 WE） earthquake signals. The modal estimates are statistically compared to their target values, proving the accuracy of the developed algorithm in providing prompt and accurate estimates of all current strong ground motion modal parameters. At this stage, such analysis tool may be employed for convenient application in the realm of Earthquake Engineering, towards potential Structural Health Monitoring and damage detection purposes.

关键词： Operational Modal Analysis （OMA） modal dynamic identification refined Frequency Domain Decomposition（rFDD） FEMA P695 seismic database earthquake response identification input

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Molecular Control of Flowering in Response to Day Length in Rice

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Journal of Integrative Plant Biology 2013年第5期55卷 410-418页

作者： Vittoria Brambilla fabio Fornara Department of Biosciences University of Milan

Flowering at the most appropriate times of the year requires careful monitoring of environmental conditions and correct integration of such information with an endogenous molecular network. Rice （Oryza sativa） is a facultative short day plant, and flowers quickly under short day lengths, as opposed to Arabidopsis thaliana whose flowering is accelerated by longer days. Despite these physiological differences, several genes controlling flowering in response to day length （or photoperiod） are conserved between rice and Arabidopsis, and the molecular mechanisms involved are similar. Inductive day lengths trigger expression of florigenic proteins in leaves that can move to the shoot apical meristem to induce reproductivedevelopment. As compared to Arabidopsis, rice also possesses unique factors that regulate expression of florigenic genes. Here, we discuss recent advances in understanding the molecular mechanisms involved in day length perception, production of florigenic signals, and molecular responses of the shoot apical meristem to florigenic proteins.

关键词： Rice florigen flowering photoperiod shoot apical meristem.

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Extremely low frequency electromagnetic fields stimulation modulates autoimmunity and immune responses：a possible immuno-modulatory therapeutic effect in neurodegenerative diseases

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Neural Regeneration Research 2016年第12期11卷 1888-1895页

作者： fabio Guerriero Giovanni Ricevuti Department of Internal Medicine and Medical Therapy Section of Geriatrics University of Pavia Pavia Italy Azienda di Servizi alia Persona Istituto di Cura Santa Margherita of Pavia Pavia Italy

Increasing evidence shows that extremely low frequency electromagnetic fields（ELF-EMFs） stimulation is able to exert a certain action on autoimmunity and immune cells. In the past, the efficacy of pulsed ELFEMFs in alleviating the symptoms and the progression of multiple sclerosis has been supported through their action on neurotransmission and on the autoimmune mechanisms responsible for demyelination. Regarding the immune system, ELF-EMF exposure contributes to a general activation of macrophages, resulting in changes of autoimmunity and several immunological reactions, such as increased reactive oxygen species-formation, enhanced phagocytic activity and increased production of chemokines. Transcranial electromagnetic brain stimulation is a non-invasive novel technique used recently to treat different neurodegenerative disorders, in particular Alzheimer＇s disease. Despite its proven value, the mechanisms through which EMF brain-stimulation exerts its beneficial action on neuronal function remains unclear. Recent studies have shown that its beneficial effects may be due to a neuroprotective effect on oxidative cell damage. On the basis of in vitro and clinical studies on brain activity, modulation by ELF-EMFs could possibly counteract the aberrant pro-inflammatory responses present in neurodegenerative disorders reducing their severity and their onset. The objective of this review is to provide a systematic overview of the published literature on EMFs and outline the most promising effects of ELF-EMFs in developing treatments of neurodegenerative disorders. In this regard, we review data supporting the role of ELF-EMF in generating immune-modulatory responses, neuromodulation, and potential neuroprotective benefits. Nonetheless, we reckon that the underlying mechanisms of interaction between EMF and the immune system are still to be completely understood and need further studies at a molecular level.

关键词： electromagnetic fields Alzheimer＇s disease transcranial magnetic stimulation autoimmunity immunomodulation

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A novel distributed architecture for unmanned aircraft systems based on Robot Operating System 2

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IET Cyber-Systems and Robotics 2023年第1期5卷 9-23页

作者： Lorenzo Bianchi Daniele Carnevale fabio Del Frate Roberto Masocco Simone Mattogno Fabrizio Romanelli Alessandro Tenaglia Department of Civil Engineering and Computer Science Engineering University of Rome“Tor Vergata”RomeItaly

A novel distributed control architecture for unmanned aircraft system (UASs) based on thenew Robot Operating System (ROS) 2 middleware is proposed, endowed with industrialgradetools that establish a novel standard for high-reliability distributed systems. Thearchitecture has been developed for an autonomous quadcopter to design an inclusivesolution ranging from low-level sensor management and soft real-time operating systemsetup and tuning to perception, exploration, and navigation modules orchestrated by afinite-state machine. The architecture proposed in this study builds on ROS 2 with itsscalability and soft real-time communication functionalities, while including security andsafety features, optimised implementations of localisation algorithms, and integrating aninnovative and flexible path planner for UASs. Finally, experimental results have beencollected during tests carried out both in the laboratory and in a realistic environment,showing the effectiveness of the proposed architecture in terms of reliability, scalability, andflexibility.

关键词： navigation robot perception slam(robots) unmanned aerial vehicle

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Attributes of stand-age-dependent forest determine technosol fertility of Atlantic forest re-growing on mining tailings in Mariana,Brazil

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Journal of Forestry Research 2022年第1期33卷 103-116页

作者： Pedro Manuel Villa Sebastião Venâncio Martins Aline Pilocelli Gabriel Correa Kruschewsky Andreia Aparecida Dias fabio Haruki Nabeta Forest Restoration Laboratory Department of Forest EngineeringUniversidade Federal de ViçosaViçosaMinas GeraisBrazil Fundação Renova Belo HorizonteMinas GeraisBrazil

Understanding how soil fertility changes due to environmental conditions and stand-age-dependent forest attributes is important for local-scale forest restoration.We evaluated the effects of stand-age-dependent forest attributes(plant community composition and litter stock)on soil and technosol fertility across two second-growth Atlantic forests(SGF)after the deposition of mining tailings in Mariana,southeastern Brazil.We hypothesized that technosol fertility in the SGF tailings is positively affected by plant community composition variability,stand age,and litter stock.We used total exchangeable bases and organic matter as fertility indicators for technosol and soil,and species composition and litter stock as stand-age-dependent forest attributes.Our results showed significant differences in the stand-age-dependent forest attributes and soil chemical properties between the two forest patches(SGF tailing and SGF non-tailing)evaluated.Thus,there was a marked gradient of litter storage and fertility between soil and technosol that can be important forest recovery indicators for the affected plant communities.Furthermore,according to the tested models,we corroborated the hypothesis that technosol fertility is positively affected by stand age,plant community composition variability,and litter stock,which may contribute considerably to forest recovery on tailings.Our results demonstrate that the fertility predictors analyzed to explain the forest recovery on tailings can also be considered as ecological indicators for assessing forest restoration in areas impacted by mining tailings in Mariana.

关键词： Ecological indicators Forest recovery Litter stock Nutrient recovery Technosol

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Virtual-reality and intelligent hardware in digital twins

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Virtual Reality & Intelligent Hardware 2022年第6期4卷 I0001-I0003页

作者： Zhihan LV Gustavo MARFIA fabio POIESI Neil VAUGHAN Jun SHEN Uppsala University Sweden University of Bologna Italy Fondazione Bruno Kessler Italy University of Exeter UK University of Wollongong Australia

Several new models and formats for the digital transformation of the manufacturing industry appear because of the rapid integration of information technology and the real economy,as well as the increasingly obvious evolution trend of industrial digitalization,networking,and intelligence.Among them,digital twins have increasingly become a research hotspot in all sectors of the industry and have broad prospects.It maps physical objects in virtual space in a digital way and simulates their behavioral characteristics in real environments.It makes the gap between virtuality and reality disappear based on their closed-loop interaction.Digital twins are undoubtedly an important and strategic technology in response to familiar products,production,and services.It can also speculate some indicators that cannot be directly measured by machine learning through collecting the direct data of limited physical sensor indicators.This can realize an assessment of the current state,a diagnosis of past problems,and a prediction of future trends,and simulate possibilities to provide more comprehensive decision support.

关键词： hardware doubt prediction

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The race for quantum supremacy: pushing the classical limit for photonic hardware

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National Science Review 2019年第1期6卷 2-3页

作者： Nicolò Spagnolo fabio Sciarrino Quantum Lab Dipartimento di FisicaSapienza Università di Roma

The strong efforts towards the realization of scalable quantum computing are motivated by the promise of super-polynomial speed-up in several computational tasks.A first fundamental step in this route is to provide concrete evidence of ‘quantum supremacy’. Such a regime is obtained when a quantum device is capable of solving a specific problem faster than the best classical hardware. A serious attempt to provide a first demonstration of quantum speed-up with affordable resources is represented by boson sampling [1,2],

关键词： The race for quantum supremacy pushing the classical limit for photonic hardware

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Fractal nature of human gastrointestinal system:Exploring a new era

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World Journal of Gastroenterology 2023年第25期29卷 4036-4052页

作者： fabio Grizzi Marco Spadaccini Maurizio Chiriva-Internati Mohamed A A A Hegazi Robert S Bresalier Cesare Hassan Alessandro Repici Silvia Carrara Department of Immunology and Inflammation IRCCS Humanitas Research HospitalRozzano 20089MilanItaly Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20072MilanItaly Division of Gastroenterology and Digestive Endoscopy Department of GastroenterologyIRCCS Humanitas Research HospitalRozzano 20089MilanItaly Departments of Gastroenterology Hepatology&NutritionDivision of Internal MedicineThe University of Texas MD Anderson Cancer CenterHoustonTX 77030United States

The morphological complexity of cells and tissues,whether normal or pathological,is characterized by two primary attributes:Irregularity and self-similarity across different scales.When an object exhibits self-similarity,its shape remains unchanged as the scales of measurement vary because any part of it resembles the whole.On the other hand,the size and geometric characteristics of an irregular object vary as the resolution increases,revealing more intricate details.Despite numerous attempts,a reliable and accurate method for quantifying the morphological features of gastrointestinal organs,tissues,cells,their dynamic changes,and pathological disorders has not yet been established.However,fractal geometry,which studies shapes and patterns that exhibit self-similarity,holds promise in providing a quantitative measure of the irregularly shaped morphologies and their underlying self-similar temporal behaviors.In this context,we explore the fractal nature of the gastrointestinal system and the potential of fractal geometry as a robust descriptor of its complex forms and functions.Additionally,we examine the practical applications of fractal geometry in clinical gastroenterology and hepatology practice.

关键词： Fractals Geometry Gastroenterology Esophagus Stomach Colon Pancreas Liver Time-series Shape Behavior

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Potential therapeutic effects of polyphenols in Parkinson's disease:in vivo and in vitro pre-clinical studies

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Neural Regeneration Research 2021年第2期16卷 234-241页

作者： Claudio Giuliano Silvia Cerri fabio Blandini Laboratory of Cellular and Molecular Neurobiology IRCCS Mondino FoundationPaviaItaly

Parkinson's disease is a neurodegenerative disorder characterized by a combination of severe motor and non-motor symptoms.Over the years,several factors have been discovered to play a role in the pathogenesis of this disease,in particular,neuroinflammation and oxidative stress.To date,the pharmacological treatments used in Parkinson's disease are exclusively symptomatic.For this reason,in recent years,the research has been directed towards the discovery and study of new natural molecules to develop potential neuroprotective therapies against Parkinson's disease.In this context,natural polyphenols have raised much attention for their important anti-inflammatory and antioxidant properties,but also for their ability to modulate protein misfolding.In this review,we propose to summarize the relevant in vivo and in vitro studies concerning the potential therapeutic role of natural polyphenols in Parkinson's disease.

关键词： alpha-synuclein anti-inflammatory antioxidants natural molecules neuroprotection Parkinson's disease polyphenols syntomatic effect

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