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Role of copper chelating agents: between old applications and new perspectives in neuroscience

Neural Regeneration Research 2025年第3期20卷 751-762页

作者： Rosalba Leuci Leonardo Brunetti Vincenzo Tufarelli Marco Cerini Marco Paparella Nikola Puvača Luca Piemontese Department of Pharmacy-Pharmaceutical Science University of Bari Aldo MoroBariItaly Department of Precision and Regenerative Medicine and Jonian Area(diMePRe-J) Section of Veterinary Science and Animal ProductionUniversity of Bari Aldo MoroBariItaly Department of Engineering Management in Biotechnology Faculty of Economics and Engineering Management in Novi SadUniversity Business Academy in Novi SadNovi SadSerbia

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

关键词： agriculture Alzheimer's disease chelators copper feed supplements multi-target

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Small heat shock protein B8:from cell functions to its involvement in diseases and potential therapeutic applications

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Neural Regeneration Research 2025年第10期20卷 2872-2886页

作者： Marta Chierichetti Riccardo Cristofani Valeria Crippa Veronica Ferrari Marta Cozzi Elena Casarotto Paola Pramaggiore Laura Cornaggia Guglielmo Patelli Ali Mohamed Margherita Piccolella Mariarita Galbiati Paola Rusmini Barbara Tedesco Angelo Poletti Laboratory of Experimental Biology Dipartimento di Scienze Farmacologiche e Biomolecolari“Rodolfo Paoletti”(DiSFeB)Universitàdegli Studi di MilanoMilanItaly

Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock ***8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and ***8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective *** line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and *** cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under ***,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar *** note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other *** is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial *** review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its ***-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.

关键词： aggregation autophagy cancer chaperone chaperone-assisted selective autophagy cognitive impairment HSPB8 neuroinflammation neuromuscular diseases therapy

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Calcium-sensitive protein MLC1 as a possible modulator of the astrocyte functional state

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Neural Regeneration Research 2025年第7期20卷 2008-2010页

作者： Elena Ambrosini Angela Lanciotti Maria Stefania Brignone Department of Neuroscience Istituto Superiore di SanitàRomeItaly

Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult *** maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.

关键词： alterations modulator maintain

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Non-Topological Domain Walls in a Model with Broken Supersymmetry

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Communications in Theoretical Physics 2011年第5期55卷 841-851页

作者： Leonardo Campanelli Marco Ruggieri dipartimento di Fisica Universita di Bari Yukawa Institute for Theoretical Physics Kyoto University

We study non-topological, charged planar walls （Q-walls） in the context of a particle physics model with supersymmetry broken by low-energy gauge mediation. Analytical properties are derived within the fiat-potential approximation for the flat-direction raising potential, while a numerical study is performed using the fall two-loop supersymmetric potential. We analyze the energetics of finite-size Q-walls and compare them to Q-balls, non-topological solitons possessing spherical symmetry and arising in the same supersymmetric model. This allows us to draw a phase diagram in the charge-transverse length plane, which shows a region where Q-wall solutions are energetically favored over Q-balls. However, due to their finiteness, such finite-size Q-walls are dynamically unstable and decay into Q-balls in a time which is less than their typical scale-length.

关键词： Q-walls non-topological solitons

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Integrin-targeting with peptide-bioconjugated semiconductor-magnetic nanocrystalline heterostructures

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Nano Research 2016年第3期9卷 644-662页

作者： Gianpiero Valente Nicoletta Depalo Ivan de Paola Rosa Maria lacobazzi Nunzio Denora Valentino Laquintana Roberto Comparelli Emiliano Altamura Tiziana Latronico Michele Altomare Elisabetta Fanizza Marinella Striccoli Angela Agostiano Michele Saviano Annarita Del Gatto Laura Zaccaro Maria Lucia Curri universita degli Studi di bari Aldo Moro Dipartimento di Chimica Via Orabona 4 70125 - Bari Italy Istituto per i Processi Chimico-Fisici-CNR UOS bari Via Orabona 4 70125 - Bari Italy Istituto di Biostrutture e Bioimmagini-CNR Via Mezzocannone 16 80134 - Napoli Italy universita degli Studi di bari Aldo Moro Dipartimento di Farmacia - Scienze del Farmaco Via Orabona 4 70125 - Bari Italy universita degli Studi di bariAIdo Moro Dipartimento di Bioscienze Biotecnologie e Biofarmaceutica Via Orabona 4 70125 - Bari Italy lstituto di Cristallografia-CNR Via Amendola 122/0 70126 Bari Italy

Binary asymmetric nanocrystals （BNCs）, composed of a photoactive TiO2 nanorod joined with a superparamagnetic γ-Fe203 spherical domain, were embedded in polyethylene glycol modified phospholipid micelle and successfully bioconjugated to a suitably designed peptide containing an RGD motif. BNCs represent a relevant multifunctional nanomaterial, owing to the coexistence of two distinct domains in one particle, characterized by high photoactivity and magnetic properties, that is particularly suited for use as a phototherapy and hyperthermia agent as well as a magnetic probe in biological imaging. We selected the RGD motif in order to target integrin expressed on activated endothelial cells and several types of cancer cells. The prepared RGD-peptide/BNC conjugates, comprehensively monitored by using complementary optical and structural techniques, demon- strated a high stability and uniform dispersibility in biological media. The cytotoxicity of the RGD-peptide/BNC conjugates was studied in vitro. The cellular uptake of RGD-peptide conjugates in the cells, assessed by means of two distinct approaches, namely confocal microscopy analysis and emission spectroscopy determination in cell lysates, displayed selectivity of the RGD-peptide-BNC conjugate for the cw]33 integrin. These RGD-peptide-BNC conjugates have a high potential for theranostic treatment of cancer.

关键词： nanocrystallineheterostructures photoactive semiconductor magnetic nanostructure cyclic RGD peptide αvβ3 integrin active targeting

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Space, Time, and Their Transformations

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Journal of Systems Engineering and Electronics 1995年第4期6卷 25-44页

作者： F.Selleri (universita di bari-dipart. di Fisica, INFN-Sezione di bari,Via Amendola 173, I-70126 bari) universita di bari-dipart. di Fisica INFN-Sezione di Bari Via Amendola 173 1-70126 Bari

We construct a set T of space-the transformations between inertial systems that are completely equivalent for explaining the experimental evidence, by starting from two empirically based assumptions: (1) The two-way velocity of light is c in all inertial systems and in all directions; (2) Time dilation effects take place with the usual relativistic factor. The Lorentz transformation is an element of T and any two elements of T differ only as to a convention regarding clock synchronization. The simplest choice is to transform time independently of space coordinates (absolute synchronization) and can be called 'inerital transformation.' When accelerations are considered the equivalence is broken and the inertial transformation emerges as closest to physical reality.

关键词： Special relativity Space and time.

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Sorafenib delivery nanoplatform based on superpara- magnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

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Nano Research 2017年第7期10卷 2431-2448页

作者： Nicoletta Depalo Rosa Maria lacobazzi Gianpiero Valente Ilaria Arduino Silvia Villa Fabio Canepa Valentino Laquintana Elisabetta Fanizza Marinella Striccoli Annalisa Cutrignelli Angela Lopedota Letizia Porcelli Amalia Azzariti Massimo Franco Maria Lucia Curri Nunzio Denora Istituto per i Processi Chimico-Fisici-CNR UOS bari Via Orabona 4 70125 Bari Italy Istituto Tumori IRCCS Giovanni Paolo II viale O. Flacco 65 70124 Bari Italy dipartimento di Chimica Universita degli Studi di Bad Aldo Moro Via Orabona70125 Bari Italy dipartimento di Farmacia-Scienze del Farmaco Universita degli Studi di Bari Aldo Moro Via Orabona 4 70125 Bari Italy dipartimento di Chimica e Chimica Industriale Universita di Genova Via Dodecaneso 31 16146 Genova Italy

Currently, sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients. Unfortunately, its side effects, particularly its overall toxicity, limit the therapeutic response that can be achieved. Superparamagnetic iron oxide nanoparticles （SPIONs） are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field, thus improving intratumoral accumulation and reducing adverse effects. Here, nanoformulations based on polyethylene glycol modified phospholipid micelles, loaded with both SPIONs and sorafenib, were successfully prepared and thoroughly investigated by complementary techniques. This nanovector system provided effective drug delivery, had an average hydrodynamic diameter of about 125 nm, had good stability in aqueous medium, and allowed controlled drug loading. Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle. An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver. Human hepatocellular carcinoma （HepG2） cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib. These experiments demonstrated that this delivery platform is able to enhance sorafenib＇s antitumor effectiveness by magnetic targeting. The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites, where selective release of sorafenib can improve its efficacy and safety profile.

关键词： superparamagnetic ironoxide nanoparticles poly(ethylene glycol) (PEG)-modified phospholipidmicelles drug delivery magnetic targeting hepatocellular carcinoma sorafenib

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How dopamine tunes parvalbumin interneurons in the hippocampus:new experimental observations in Alzheimer's disease

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Neural Regeneration Research 2025年第5期20卷 1405-1406页

作者： Livia La Barbera Paraskevi Krashia Annalisa Nobili Department of Medicine and Surgery UniversitàCampus Bio-Medico di RomaViaÁlvaro del PortilloRomeItaly Department of Experimental Neurosciences IRCCS Santa Lucia FoundationVia del Fosso di FioranoRomeItaly Department of Science and Technology for Sustainable Development and One Health UniversitàCampus Bio-Medico di RomaViaÁlvaro del PortilloRomeItaly

Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc *** is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.

关键词： Alzheimer alterations dopamine

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Calabrian and Ionian： A proposal for the definition of Mediterranean stages for the Lower and Middle Pleistocene

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Episodes 2006年第2期29卷 107-114页

作者： Maria Bianca Cita Luca Capraro Neri Ciaranfi Enrico di Stefano Maria Marino Domenico Rio Rodolfo Sprovieri Gian Battista Vai universita di Milano Dipartimento di Scienze della Terra ‘Ardito Desio＇ via Mangiagalli 34. 20133 Milano Italy universita di Padova Dipartimento di Geologia Paleontologia e Geofisica via Giottol 35137 Padova Italy universita di bari Dipartimento di Geologia e Geofisica via Orabona 4 70125 Bari Italy universita di Palermo Dipartimento di Geologia e Geodesia corso Tukory 131 90134 Palermo Italy universita di Bologna Dipartimento di Scienze della Terra e Geologico-Ambientali Piazza di Porta San Donato 140126 Bologna Italy

The need to standardise stratigraphical subdivisions of continuous marine sedimentary successions that outcrop for hundreds metres, using clearly defined points fixed in the field is strongly felt. A proposal is presented here to formalize regional stages for the Lower Pleistocene （Calabrian） and for the Middle Pleistocene （Ionian） in Italy. The sections are well exposed, carefully investigated using multiple criteria （an integrated stratigraphical approach） and located in the central part of the Mediterranean. This area is recognized worldwide as a classical region for the Neogene and the Pleistocene sequences. The terrestrial record is directly correlated with the deep-sea record, as determined from ODP Sites 653 （Tyrrhenian Sea）, 963 （Sicily Channel） and 964 （Ionian Sea）from the central Mediterranean. The present formal proposal is consistent with the INQUA and ICS decision to define and correlate the Plio/Pleistocene boundary （GSSP at Vrica） within the Olduvai Subchron, at 1.81 My, the Lower/Middle Pleistocene boundary at the Matuyama/Brunhes reversal at 0. 78 My and the Middle/ Upper Pleistocene boundary with the base of MIS 5, approximately 0. 13My. The present proposal also is consistent with the call for stage unit stratotypes that emphasize both the physical content of a stage and its boundaries （Hilgen et al., 2006）.

关键词：卡拉布里亚爱奥尼亚地中海更新世

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A Second Order Finite-difference Ghost-Point Method for Elasticity Problems on Unbounded Domains with Applications to Volcanology

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Communications in Computational Physics 2014年第9期16卷 983-1009页

作者： Armando Coco Gilda Currenti Ciro Del Negro Giovanni Russo dipartimento di Scienze della Terra e Geoambientali Universita di Bari Aldo MoroBariItaly. Bristol University Queens RoadBristol BS81RJUnited Kingdom. Istituto Nazionale di Geofisica e Vulcanologia Italy. dipartimento di Matematica e Informatica Universita di CataniaCataniaItaly

We propose a finite-difference ghost-point approach for the numerical solution of Cauchy-Navier equations in linear elasticity problems on arbitrary unbounded *** technique is based on a smooth coordinate transformation,which maps an unbounded domain into a unit *** geometries are defined by suitable level-set *** equations are discretized by classical nine-point stencil on interior points,while boundary conditions and high order reconstructions are used to define the field variables at ghost-points,which are grid nodes external to the domain with a neighbor inside the *** linear system arising from such discretization is solved by a multigrid *** approach is then applied to solve elasticity problems in volcanology for computing the displacement caused by pressure *** method is suitable to treat problems in which the geometry of the source often changes(explore the effects of different scenarios,or solve inverse problems in which the geometry itself is part of the unknown),since it does not require complex re-meshing when the geometry is *** numerical tests are successfully performed,which asses the effectiveness of the present approach.

关键词： Linear elasticity Cauchy-Navier equations ground deformation unbounded domain coordinate transformation method Cartesian grid ghost points level-set methods multigrid.

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