Biology subjects

Fumagalli, S.

Publications and source records attributed to Fumagalli, S..

4 recordsLinked to original sources

bioRxiv2026

Glycan-coated nanoparticles mimicking the ischemic glycocalyx scavenge the complement system conferring protection after experimental ischemic stroke

Glycoproteins lining the luminal endothelial surface form the glycocalyx, composing the tripartite blood brain barrier. We explored the glycocalyx as a source of danger signals for complement lectin pathway after ischemic stroke. Our data indicate that hypoxic microvascular cells increased -D-mannosyl and N-acetylglucosaminyl exposure after re-oxygenation, favoring mannose binding lectin (MBL) pathogenic deposition, and overexpression of inflammatory genes (ICAM-1 and MMP-2). The hypoxia-conditioned medium induced neuronal damage (reduced MAP-2), microglia and astrocytic reactivity (increased/thickened ramifications) when applied to induced pluripotent stem cell-derived neurons, astrocytes and microglia co-cultures. All these effects were counteracted by mannose-capped gold nanoparticles (Man-GNPs), shown to bind and sequester MBL from the medium. We then tested the Man-GNPs in vivo, in an ischemic stroke model using humanized mice, knocked-in for human MBL. The ischemic mice (males:females 1:1) treated with Man-GNPs (3h after the ischemic onset) exhibited less anxiety at the elevated plus maze and reduced neuronal loss at 8d after ischemia compared to vehicle-treated. Thus, multivalent Man-GNPs represent a promising approach to take MBL away from its glycoproteic targets on the ischemic endothelium, hence preventing downstream pathogenesis. Moreover, these data support circulating MBL as a druggable pharmacological target to prevent the thrombo-inflammatory events following acute brain injury.

neuroscience↗

bioRxiv2025

Multi-center Translational Trial of Remote Ischemic Conditioning in Acute Ischemic Stroke (TRICS BASIC)

BackgroundBasic science studies have reported remote ischemic conditioning (RIC) as neuroprotective in acute ischemic stroke, while clinical evidence remains conflicting. The TRICS BASIC study investigated the efficacy and safety of RIC in experimental ischemic stroke using a rigorous clinical trial methodology. MethodsMulti-center, multi-species, parallel group, randomized, controlled, preclinical trial of transient femoral artery clipping to induce RIC in female and male rats and mice subjected to transient endovascular occlusion of the middle cerebral artery. Animals were randomized to receive RIC, or sham surgery, after reperfusion. The primary endpoint was good functional outcome at 48 hours, assessed using a composite functional neuroscore. Secondary endpoints was infarct volume at 48 hours and safety, assessed using a standardized health report at 24 and 48 hours. Pre-enrollment harmonization, centralized monitoring, allocation concealment, blinded outcome assessment and intention-to-treat analysis were applied. ResultsThe trial enrolled 164 rodents (82 mice and 82 rats) of both sexes (53% females), across seven laboratories. A greater proportion of RIC-treated rodents achieved a favorable functional outcome compared to controls, at 48 hours post-ischemia (55% versus 36%; OR 2.2, 95% CI [1.23-4.4], p=0.009). RIC was associated with a small reduction in infarct volume (standardized mean difference -0.38, 95% CI [-0.70, -0.05], p=0.024). Health monitoring indicated no major safety concerns, and post-operative analgesia requirements were lower in RIC-treated mice. ConclusionsSurgically-induced RIC provided a modest but evident neuroprotective effect in experimental ischemic stroke, underscoring the potential of this strategy as an adjunctive treatment in stroke care. The findings of the TRICS BASIC study highlighted the importance of multicenter preclinical trials in addressing variability and enhancing translational validity. Registrationregistered at preclinicaltrials.eu, identifier PCTE0000177.

neuroscience↗

bioRxiv2024

Data Hunters: bridging bioinformatics education and microbiome research

Vast sequencing data in public repositories offer researchers unprecedented opportunities for gaining insights through reanalysis and machine learning approaches, thereby advancing the microbiology field. However, the lack of standardized metadata poses a significant obstacle to big data reuse, necessitating advanced bioinformatics skills for curation and integration. To tackle this challenge, we organized the Data Hunters Workshop, enabling extensive human skin microbiome metadata curation through student community engagement. The Data Hunters Workshop constitutes a student-science initiative within the University of Milano-Bicocca, Italy. Integrating theoretical and hands-on phases, the workshops structure included a 6-hour lecture, covering metagenomics and metadata manipulation fundamentals, followed by an interactive practical phase designed as a learn-and-play activity. This phase was supported by in-house developed educational online and command-line resources, facilitating students acquisition of Python commands for managing microbiome metadata. Upon the workshops conclusion, its effectiveness was assessed through surveys and standardized evaluation scales. Twenty-nine students addressed the critical challenge of metagenomics metadata standardization. Workshops resources have equipped students with foundational knowledge in metagenomics and Python programming, empowering them to curate metadata from 379 amplicon-based and shotgun sequencing projects of the human skin microbiome. The collaborative endeavors of these students will ensure the construction of a curated metadata collection. The Data Hunters Workshop established a reusable model for similar educational aims, facilitating metagenomics and bioinformatics teaching and metadata curation. It bridged education and microbiome research by focusing on human skin microbiome metadata curation, ultimately striving to construct a specific collection promptly accessible to researchers.

scientific communication and education↗

bioRxiv2023

MADAME: a user-friendly bioinformatic tool for data and metadata retrieval in microbiome research

Microbiome research advancements have provided countless insights. Despite the massive amount of data currently stored in public repositories, these resources remain vastly underutilized due to the intricacy of data and metadata retrieval from these databases. However, leveraging data-driven approaches is crucial for microbiome research progress by overcoming variations between studies and identifying generalizable trends. We designed the open-access and user-friendly bioinformatic tool MADAME (MetADAta MicrobiomE) to streamline the data and metadata retrieval process. MADAME addresses the challenges posed by the public repositories current limitations, allowing users to retrieve publications associated with the accession codes of interest. Additionally, MADAME allows users to visually explore retrieved results through the generation of a comprehensive report with plots and statistics. These unique features of MADAME let users maximize their time and resources, enabling them to assess metadata suitability before pursuing data download. To showcase its diverse functionalities, we recreate several scenarios to meet the diverse requirements that researchers may have.

bioinformatics↗