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Astrocytes greatly participate to inflammatory and neurotoxic reactions occurring in neurodegenerative diseases and are valuable pharmacological targets to support neuroprotection. Here we used human astrocytes generated from reprogrammed fibroblasts as a cellular model to study the effect of the compound Laquinimod and its active metabolite de-Laquinimod on astrocyte functions and the astrocyte–neuron interaction. We show that human iAstrocytes expressed the receptor for the inflammatory mediator IL1 and responded to it via nuclear translocation of NFκB, an event that did not occur if cells were treated with Laquinimod, indicating a direct anti-inflammatory activity of the drug on the human astrocyte. Similarly, while exposure to IL1 downregulated glial glutamate transporters GLAST and GLT1, treatment with Laquinimod supported maintenance of physiological levels of these proteins despite the inflammatory milieu. Laquinimod also induced nuclear translocation of the aryl hydrocarbon receptor (AHR), suggesting that drug action was mediated by activation of the AHR pathway. However, the drug was effective despite AHR inhibition via CH223191, indicating that AHR signaling in the astrocyte is dispensable for drug responses. Finally, in vitro experiments with rat spinal neurons showed that laquinimod did not exert neuroprotection directly on the neuron but dampened astrocyte-induced neurodegeneration. Our findings indicate that fibroblast-derived human astrocytes represent a suitable model to study astrocyte–neuron crosstalk and demonstrate indirect, partial neuroprotective efficacy for laquinimod.

Demyelination is a key pathogenic feature ofmultiple sclerosis (MS). Here, we evaluated the astrocyte contribution to myelin loss and focused on the neurotrophin receptor TrkB, whose up-regulation on the astrocyte finely demarcated chronic demyelinated areas in MS and was paralleled by neurotrophin loss. Mice lacking astrocyte TrkB were resistant to demyelination induced by autoimmune or toxic insults, demonstrating that TrkB signaling in astrocytes fostered oligodendrocyte damage. In vitro and ex vivo approaches highlighted that astrocyte TrkB supported scar formation and glia proliferation even in the absence of neurotrophin binding, indicating TrkB transactivation in response to inflammatory or toxic mediators. Notably, our neuropathological studies demonstrated copper dysregulation in MS and model lesions and TrkB-dependent expression of copper transporter (CTR1) on glia cells during neuroinflammation. In vitro experiments evidenced that TrkB was critical for the generation of glial intracellular calcium flux and CTR1 up-regulation induced by stimuli distinct from neurotrophins. These events led to copper uptake and release by the astrocyte, and in turn resulted in oligodendrocyte loss. Collectively, these data demonstrate a pathogenic demyelination mechanism via the astrocyte release of copper and open up the possibility of restoring copper homeostasis in the white matter as a therapeutic target in MS.

Animal models provide an important tool to investigate the pathogenesis of neuromuscular disorders. In the present study, we analyze fiber composition of the brachial plexus branches to the pectoral muscles: the medial anterior thoracic nerve (MATN) and the lateral anterior thoracic nerve (LATN). The morphological and morphometric characteristics and the percentage of motor fibers within each nerve are here reported, adding information to microscopic anatomy knowledge of the rat brachial plexus. As control, we employed the quadriceps nerve, commonly used for the evaluation of motor fibers at hindlimbs. We demonstrated that the MATN and the LATN are predominantly composed of large motor fibers and therefore could be employed to evaluate the peripheral nervous system (PNS) involvement at forelimbs in neurological diseases models, predominantly affecting the motor fiber compartment.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia. The accurate and continuous monitoring of these symptoms is essential for optimizing treatment strategies and improving patient outcomes. Traditionally, clinical assessments have relied on scales and methods that often lack the ability for continuous, real-time monitoring and can be subject to interpretation bias. Recent advancements in wearable technologies, such as smartphones, smartwatches, and activity trackers (ATs), present a promising alternative for more consistent and objective monitoring. This review aims to evaluate the use of smartphones and smart wrist devices, like smartwatches and activity trackers, in the management of PD, assessing their effectiveness in symptom evaluation and monitoring and physical performance improvement. Studies were identified by searching in PubMed, Scopus, Web of Science, and Cochrane Library. Only 13 studies of 1027 were included in our review. Smartphones, smartwatches, and activity trackers showed a growing potential in the assessment, monitoring, and improvement of motor symptoms in people with PD, compared to clinical scales and research-grade sensors. Their relatively low cost, accessibility, and usability support their integration into real-world clinical practice and exhibit validity to support PD management.

Background Adult-onset Still’s disease (AOSD) is rare inflammatory disease of unknown etiology that usually affects young adults. The more common clinical manifestations are spiking fevers, arthritis, evanescent rash, elevated liver enzymes, lymphadenopathy, hepatosplenomegaly, and serositis. The multi-visceral involvement of the disease and the different complications, such as macrophage activation syndrome, may strongly decrease the life expectancy of AOSD patients. Methods This study aimed to identify the positive and negative features correlated with the outcome of patients. A retrospective analysis of AOSD patients prospectively admitted to three rheumatologic centers was performed to identify the clinical features present at the time of diagnosis and to predict the possible outcome. Furthermore, we investigated the as yet to be validated prognostic value of the systemic score previously proposed. Results One hundred consecutive AOSD patients were enrolled. The mean systemic score showed that the majority of patients had a multi-organ involvement. Sixteen patients showed different complications, mainly the macrophage activation syndrome. A strong increase of inflammatory markers was observed. All patients received steroids at different dosages, 55 patients in association with immunosuppressive drugs and 32 in association with biologic agents. Sixteen patients died during the follow-up. Regression analysis showed that the higher values of the systemic score and the presence of AOSD-related complications, assessed at the time of diagnosis, were significantly correlated with patient mortality. A prognostic impact of the systemic score of ≥ 7.0 was reported. Conclusions Our study showed that a higher systemic score and the presence of AOSD-related complications at the time of diagnosis were significantly associated with mortality. Of note, a cut-off at 7.0 of the systemic score showed a strong prognostic impact in identifying patients at risk of AOSD-related death.

Introduction: The figure-of-eight walk test (F8WT) assesses gait on a curved path, reflecting everyday walking complexity. Despite recognized validity among elderly individuals, its application in neurological disorders remains inadequately explored. This scoping review summarizes evidence regarding F8WT use, validity, and clinical applicability among individuals with neurological disorders. Methods: A systematic literature search was conducted in the PubMed, Scopus, Embase, and Web of Science databases. After reading the full text of the selected studies and applying predefined inclusion criteria, seven studies, involving participants with multiple sclerosis (n = 3 studies), Parkinson’s disease (n = 2 studies), and stroke (n = 2 studies), were included based on pertinence and relevance to the topic. Results: F8WT demonstrated strong reliability and validity across various neurological populations and correlated significantly with established measures of gait, balance, and disease severity. Preliminary evidence supports its ability to discriminate individuals at increased fall risk and detect subtle motor performance changes. Discussion: The F8WT emerges as a valuable tool, capturing multifaceted gait impairments often missed by linear walking assessments. Sensitive to subtle functional changes, it is suitable for tracking disease progression and intervention efficacy. Conclusions: F8WT is reliable and clinically relevant, effectively identifying subtle, complex walking impairments in neurological disorders.

Graphene quantum dots (GQD), the new generation members of graphene-family, have shown promising applications in anticancer therapy. In this study, we report the synthesis of a fluorescent and biocompatible nanovector, based on GQD, for the targeted delivery of an anticancer drug with benzofuran structure (BFG) and bearing the targeting ligand riboflavin (RF, vitamin B2). The highly water-dispersible nanoparticles, synthesized from multi-walled carbon nanotubes (MWCNT) by prolonged acidic treatment, were linked covalently to the drug by means of a cleavable PEG linker while the targeting ligand RF was conjugated to the GQD by π–π interaction using a pyrene linker. The cytotoxic effect of the synthesized drug delivery system (DDS) GQD-PEG-BFG@Pyr-RF was tested on three cancer cell lines and this effect was compared with that exerted by the same nanovector lacking the RF ligand (GQD-PEG-BFG) or the anticancer drug (GQD@Pyr-RF). The results of biological tests underlined the low cytotoxicity of the GQD sample and the cytotoxic activity of the DDS against the investigated cancer cell lines with a higher or similar potency to that exerted by the BFG alone, thus opening new possibilities for the use of this drug or other anticancer agents endowed of cytotoxicity and serious side effects.

People with multiple sclerosis (PwMS) often experience motor impairments that require long-term rehabilitation. In recent years, digital technologies such as mobile applications and sensor-based systems, have been explored as tools to support motor rehabilitation in this population. However, their implementation in real-world settings critically depends on usability, which influences user engagement, adherence, and integration into clinical practice. To systematically review the usability, acceptability, and preliminary clinical impact of digital rehabilitation interventions targeting motor function in pwMS. A systematic literature search was conducted in PubMed, Scopus, Embase, and Web of Science up to June 2025, to identify studies that evaluated usability within the context of motor rehabilitation interventions delivered through digital platforms. Only studies involving pwMS were included. Nine studies were included. Interventions employed Kinect-based exergaming, mobile applications, pressure-sensitive platforms, and wearable sensors. Usability was generally high, with System Usability Scale (SUS) scores >70 in several studies. Adherence ranged from moderate to high, particularly when interventions incorporated real-time feedback, personalization, and user-centered design. Preliminary improvements were observed in gait speed, balance, cognitive-motor function, and physical activity levels. Digital rehabilitation tools demonstrate promising usability and feasibility for motor rehabilitation in pwMS. Personalized, interactive systems designed with user-centered approaches may enhance engagement and support behavioural activation. Future large-scale trials with standardized outcomes are needed to establish clinical effectiveness and inform integration into routine care. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251125034, PROSPERO CRD420251125034.

Background/Objectives: Multiple sclerosis (MS) is a chronic neurodegenerative disorder mainly affecting young adults and can greatly impair quality of life (QoL). Among its often overlooked but significant symptoms are bowel dysfunctions (BD), such as constipation and fecal incontinence, which can impact physical, emotional, and social well-being, especially in younger patients. This study aims to investigate the impact of BD on the QoL in young adults diagnosed with relapsing-remitting MS (RRMS) and mild disability. Methods: This retrospective cross-sectional study examined the effect of BD on QoL in 110 young adults with RRMS and mild disability (EDSS ≤ 3.5). Bowel symptoms were assessed using the Wexner Incontinence and Constipation Scales, while QoL was measured with the MSQoL-54 questionnaire. Statistical analyses were performed to examine correlations between BD severity and QoL domains. Results: Our findings showed significant correlations between the severity of intestinal symptoms and different domains of QoL, like physical functioning, emotional well-being, and social functioning. Abdominal pain and liquid fecal incontinence were especially linked to lower mental and physical health scores. Subgroup analyses also indicated gender-specific vulnerabilities, with women showing distinct effects on social and emotional dimensions. Conclusion: BD represents an important burden on bowel dysfunctions for young people with MS, deeply impacting various dimensions of QoL. This underscores an urgent need for an integrated, multidisciplinary care model that tackles physical symptoms but also psychological and social challenges. A holistic clinical strategy is vital to improving the overall well-being of this population.

Drug delivery into the vitreous chamber remains a great challenge in the pharmaceutical industry due to the complex anatomy and physiology of the eye. Intravitreal injection is the mainstream route of drug administration to the posterior segment of the eye. The purpose of this review is to assess the current literature about the widening use of the intravitreal 0.7 mg dexamethasone (Dex) implant, and to provide a comprehensive collection of all the ocular disorders that benefit from Dex administration. Although anti-vascular endothelial growth-factors (VEGFs) have been largely indicated as a first-choice level, the Dex implant represents an important treatment option, especially in selected cases, such as vitrectomized eyes or patients in whom anti-VEGF failed or are contraindicated. In this article, the safety profile as well as the list of the possible complications related to intravitreal Dex injection are also discussed.