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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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SPL transcription factors prevent inflorescence reversion in rice

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Molecular Plant 2021年第7期14卷 1041-1043页

作者： Francesca Giaume fabio Fornara Department of Biosciences University of MilanVia Celoria 2620133 MilanItaly

Plants show an incredible diversity of forms,dimensions,archi-tectures,structures,and reproductive ***,they can be geometrically described as composed of simple building units called phytomers,which are produced by the shoot apical meri-stem(SAM).A phytomer is made up of a node bearing a leaf and an axillary meristem,and of an internode connecting the node to the following *** of phytomers creates the plant body,similarly to a LEGO construction made of simple *** of the phytomeric unit creates *** leaf can change in size and shape;the axillary meristem can be dormant or active,determinate or indeterminate;the internode can elongate considerably,or be compressed to the extent it might look invisible.

关键词： connecting dimensions visible

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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 Quorum Sensing Active Matter in a Confined Geometry

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Chinese Physics Letters 2023年第10期40卷 34-38页

作者：周雨欣李云云 fabio Marchesoni MOE Key Laboratory of Advanced Micro-Structured Materials and Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology School of Physics Science and EngineeringTongji UniversityShanghai 200092China Dipartimento di Fisica Universit`a di CamerinoI-62032 CamerinoItaly

Inspired by the problem of biofilm growth,we numerically investigate clustering in a two-dimensional suspension of active(Janus)particles of finite size confined in a circular *** dynamics is regulated by a non-reciprocal mechanism that causes them to switch from active to passive above a certain threshold of the perceived near-neighbor density(quorum sensing).A variety of cluster phases,i.e.,glassy,solid(hexatic)and liquid,are observed,depending on the particle dynamics at the boundary,the quorum sensing range,and the level of noise.

关键词： Active glassy reciprocal

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Compact Differential Evolution Light: High Performance Despite Limited Memory Requirement and Modest Computational Overhead

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Journal of Computer Science & Technology 2012年第5期27卷 1056-1076页

作者： Giovanni Iacca fabio Caraffini Ferrante Neri EDepartment of Mathematical Information Technology University of JyvskylP.O.Box 35(Agora) Department of Mathematical Information Technology University of JyvskylP.O.Box 35(Agora)

Compact algorithms are Estimation of Distribution Algorithms which mimic the behavior of population-based algorithms by means of a probabilistic representation of the population of candidate solutions. These algorithms have a similar behaviour with respect to population-based algorithms but require a much smaller memory. This feature is crucially important in some engineering applications, especially in robotics. A high performance compact algorithm is the compact Differential Evolution （cDE） algorithm. This paper proposes a novel implementation of cDE, namely compact Differential Evolution light （cDElight）, to address not only the memory saving necessities but also real-time requirements, cDElight employs two novel algorithmic modifications for employing a smaller computational overhead without a performance loss, with respect to cDE. Numerical results, carried out on a broad set of test problems, show that cDElight, despite its minimal hardware requirements, does not deteriorate the performance of cDE and thus is competitive with other memory saving and population-based algorithms. An application in the field of mobile robotics highlights the usability and advantages of the proposed approach.

关键词： differential evolution compact optimization real-time optimization

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Methane Direct Conversion on Mo/ZSM-5 Catalysts Modified by Pd and Ru

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Journal of Natural Gas Chemistry 2006年第2期15卷 82-86页

作者： Priscila Dias Sily fabio Bellot Noronha fabio Barboza Passos Departamento de Engenharia Química Universidade Federal FluminenseRua Passo da Pátria156 Niterói -RJ CEP 24210-240Brazil Instituto Nacional de Tecnologia Av. Venezuela 82Rio de Janeiro -RJ CEP 20081-312Brazil Departamento de Engenharia Química Universidade Federal FluminenseRua Passo da Pátria156 Niterói-RJ CEP 24210-240Brazil

The effect of addition of Ru and Pd to Mo/HZSM-5 catalysts used in the dehydroaromatization of methane was investigated. Catalytic tests and temperature-programmed oxidation results showed that Pd-based catalysts were more selective to naphthalene and suffered strong deactivation. The presence of Ru improved the activity and stability, with a decrease in the carbonaceous deposit probably because of a mechanism of protection of the Mo2C surface.

关键词： methane Pd Ru Mo ZSM-5 dehydroaromatization

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Interventional treatment options for management of delayed arterial hemorrhage after major hepato-pancreatic-biliary surgery

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Hepatobiliary & Pancreatic Diseases International 2023年第6期22卷 648-649页

作者： Benedetto Ielpo Salvatore Alborino Emmanuel Melloul fabio Salvatori Quirino Lai Massimo Rossi Nicolas Demartines Salomone Di Saverio Unidad de Cirugía Hepatobiliopancreática Hospital del MarBarcelonaSpain Interventional Radiology Unit Macerata HospitalMacerataAV4ASUR MarcheItaly HBP and Liver Transplant Surgery Unit Visceral Surgery DeptCHUVUniversity of LausanneLausanneSwitzerland HBP and Liver Transplant Surgery Unit Policlinico Umberto ILa Sapienza University of RomeRomeItaly General Surgery Unit San Benedetto del Tronto HospitalSan Benedetto del TrontoAV5ASUR MarcheItaly

Hilar cholangiocarcinoma is a biliary malignancy arising from the perihilar biliary tree,which is associated with poor oncological outcomes due to its aggressive biology,chemo-resistance and insidious onset[1].As stated by Di Martino et al.,the standard of care is radical resection,and during the last decades,there have been great efforts to improve survival of potentially resectable hilar cholangiocarcinoma,with surgery being the treatment associated with longer survival[2].However,radical resection still represents a challenging operation with high risk of intraoperative and postoperative complications.

关键词： biliary surgery

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Diagnosis, seismic analysis and reinforcement of an old building in El-Maleh, Algeria

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Earthquake Engineering and Engineering Vibration 2010年第4期9卷 577-586页

作者： Nadir Boumechra fabio Casciati Karim Hamdaoui Department of Civil Engineering University Abou Bekr Belkaid of Tlemcen Department of Structural Mechanics University of Pavia

The Northern part of Algeria is considered to be the most active seismogenic area in the Western Mediterranean region. This area has a rich history of seismicity and had experienced many destructive earthquakes such as the Chlef （1954）, El-Asnam （1980）, Beni-Chograne （1994）, AYn-Temouchent （1999） and recently Boumerdes （2003） earthquakes. The earthquake of AYn-Temouchent on December 22, 1999, was of magnitude 5,7, killed at least 28 people and made thousands of families homeless. Consequent damage was seen in all the structures located in a radius of 30 kin. In the city of E1-Maleh, located 12 km northeast of Ain-Temouchent, the ＂The National Bank Branch＂ of E1-Maleh suffered moderate damage, but enough to justify questions about its safety. The project of rehabilitating this building required a broad analysis of its static and dynamic, past and present behaviors. The study reported in this paper was a necessary preliminary step toward the development of an optimal retrofit solution.

关键词： old masonry structure structural analyses modeling retrofit

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Performance of a base isolator with shape memory alloy bars

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Earthquake Engineering and Engineering Vibration 2007年第4期6卷 401-408页

作者： fabio Casciati Lucia Faravelli Karim Hamdaoui Dept. of Structural Mechanics University of Pavia Pavia Italy

A new and innovative base isolation device is introduced in this paper based on extensive research carried out by the authors and their co-workers. A prototype of the device was built and experimentally tested on the shaking table. The new base isolation device consists of two disks, one vertical cylinder with an upper enlargement sustained by three horizontal cantilevers, and at least three inclined shape memory alloy （SMA） bars. The role of the SMA bars is to limit the relative motion between the base and the superstructure, to dissipate energy by their super-elastic constitutive law and to guarantee the re-centring of the device. To verify the expected performance, a prototype was built and tested under sinusoidal waves of displacement of increasing frequency with different amplitudes. It is shown that the main feature of the proposed base isolation device is that for cyclic loading, the super-elastic behavior of the alloy results in wide load-displacement loops, where a large amount of energy is dissipated.

关键词： base isolator dynamic excitation energy dissipation shape memory alloy shaking table test

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