Biology subjects

Borghi, E.

Publications and source records attributed to Borghi, E..

7 recordsLinked to original sources

bioRxiv2026

Identification of ICAM-1-targeting DNA aptamers as a host-directed strategy to inhibit Human Rhinovirus infection

Exacerbations of respiratory viral infections significantly contribute to morbidity and healthcare burden. Among these viruses, Human Rhinoviruses (HRVs) are the most frequent causative agents of upper respiratory tract infections. To date, over 150 HRV serotypes have been identified, classified into three species: HRV-A, HRV-B, and HRV-C. No antiviral therapies are currently available against this viral family, largely due to the high serotype diversity and limited cross-protection. The major group of HRVs relies on the Intercellular Adhesion Molecule-1 (ICAM-1) receptor to infect airway epithelial cells, making ICAM-1 an attractive target for broad-spectrum therapeutic interventions. Here, we report the development of nucleic acid-based aptamers designed to disrupt ICAM-1-HRV binding and thereby prevent viral infection. Aptamers are single-stranded DNA molecules that fold into precise three-dimensional structures, enabling highly specific protein recognition. Using a Systematic Evolution of Ligands by EXponential Enrichment (SELEX) approach guided by a minimal peptide mimicking the ICAM-1 viral binding interface, a library of >1024 random single-stranded DNA sequences was screened. Through iterative rounds of selection, we identified eight candidate 77-nt DNA aptamers, which were subsequently evaluated for their potential using in silico and in vitro assays, as well as functional assays in human epithelial cells. From this strategy, two lead aptamers were selected that effectively inhibited HRV-A16 replication in a concentration-dependent manner, as measured by viral titers (TCID assay) and viral RNA quantification by RT-PCR. These findings demonstrate the potential of ICAM-1-targeting aptamers as antiviral agents capable of preventing HRV entry. By targeting a host receptor and creating a protective barrier at the cell surface, this approach may offer a broadly applicable strategy against multiple HRV serotypes, paving the way for the development of novel antiviral interventions. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/717810v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@130d8org.highwire.dtl.DTLVardef@2dd09borg.highwire.dtl.DTLVardef@1da744eorg.highwire.dtl.DTLVardef@109ea5b_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2025

Mesodermal-specific MECP2 expression in Drosophila induces visceral and skeletal muscle defects rescued by butyrate supplementation

BackgroundPatients affected by Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) experience disabling muscle weakness and gastrointestinal dysmotility of unclear origin. Whether these defects arise cell-autonomously, rather than secondarily to neural dysfunction, and which developmental windows are most vulnerable to MeCP2 disfunction remains unresolved. MeCP2 is a dosage-sensitive transcriptional regulator, whose functions are tightly linked to chromatin states. Because short-chain fatty acids (SCFAs) are known to inhibit histone deacetylases (HDACs), a tractable in vivo model is needed to test the effect of HDAC modulation on muscle defects. MethodsWe misexpressed human MECP2 in the Drosophila melanogaster mesoderm that gives rise to skeletal and visceral muscles. We analyzed quantitatively their morphology and function. To assess the effects of SCFA supplementation, we also supplemented diets with sodium butyrate (NaB), Lalbaay(R), a NaB-containing supplement, acetate (AcOH), and valproate (VPA). FindingsMECP2 misexpression caused pre-eclosion lethality, thinning of larval skeletal fibers with nuclear mispositioning and altered mitochondria. Functionally, it reduced locomotion, decreased food transit and gut peristalsis. Phenotypes were strongest when expression began during development. NaB and VPA supplementation rescue most of these phenotypes, consistent with their histone-deacetylase (HDAC) activity. Defects were not observed upon comparable misexpression of an RTT-associated MeCP2 loss-of-function variant, indicating that they might be relevant to pathogenesis of MECP2-related disorders. InterpretationOur genetic in vivo analysis models peripheral effects of MeCP2 dysregulation and their amelioration, supporting the possibility of HDAC-targeted strategies for MECP2-related muscle and gastrointestinal dysfunction.

genetics↗

bioRxiv2024

Late Miocene transformation of Mediterranean Sea biodiversity

Understanding deep-time marine biodiversity change under the combined effects of climate and connectivity changes is fundamental for predicting the impacts of modern climate change in semi-enclosed seas. We quantify the Late Miocene-Early Pliocene (11.63-3.6 Ma) taxonomic diversity of the Mediterranean Sea for calcareous nannoplankton, dinocysts, foraminifera, ostracods, corals, molluscs, bryozoans, echinoids, fishes, and marine mammals. During this time, marine biota was affected by global climate cooling and the restriction of the Mediterraneans connection to the Atlantic Ocean that peaked with the Messinian Salinity Crisis. Although the net change in species richness from the Tortonian to the Zanclean varies by group, species turnover is greater than 30% in all cases. The results show clear perturbation already in the pre-evaporitic Messinian (7.25-5.97 Ma), with patterns differing among groups and sub-basins.

paleontology↗

bioRxiv2023

Gut microbiota profile in CDKL5 deficiency disorder patients as a potential marker of clinical severity

CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by global developmental delay, early-onset seizures, intellectual disability, visual and motor impairments. Unlike Rett Syndrome (RTT), CDD lacks a clear regression period. CDD patients frequently encounter gastrointestinal (GI) disturbances and exhibit signs of subclinical immune dysregulation. However, the underlying causes of these conditions remain elusive. Emerging studies indicate a potential connection between neurological disorders and gut microbiota, an area completely unexplored in CDD. We conducted a pioneering study, analyzing fecal microbiota composition in CDD patients and their healthy relatives. Notably, differences in intestinal bacterial diversity and composition were identified in CDD patients. We further investigated microbiota changes based on the severity of GI issues, seizure frequency, sleep disorders, food intake type, impairment in neuro-behavioral features (assessed through the RTT Behaviour Questionnaire - RSBQ), and ambulation capacity. Our findings hint at a potential connection between CDD, microbiota, and symptom severity. This study marks the first exploration of the gut-microbiota-brain axis in CDD patients. It adds to the growing body of research emphasizing the role of the gut microbiota in neurodevelopmental disorders and opens doors to potential interventions that target intestinal microbes with the aim of improving the lives of CDD patients.

microbiology↗

bioRxiv2021

The gut microbiota of environmentally enriched mice regulates visual cortical plasticity

Exposing animals to an enriched environment (EE) has dramatic effects on brain structure, function and plasticity. The poorly known "EE derived signals" mediating the EE effects are thought to be generated within the central nervous system. Here, we shift the focus to the body periphery, revealing that gut microbiota signals are crucial for EE-driven plasticity. Developmental analysis of intestinal bacteria composition in EE mice revealed striking differences from standard condition (ST) animals and enhanced levels of short-chain fatty acids (SCFA). Depleting the EE mice gut microbiota with an antibiotic cocktail decreased SCFA and prevented EE induction of adult ocular dominance (OD) plasticity, spine dynamics and microglia rearrangement. SCFA treatment in ST mice mimicked the EE induction of adult OD plasticity and morphological microglial rearrangement. Remarkably, transferring the microbiota of EE mice to ST recipients activated adult OD plasticity. Thus, taken together our data suggest that experience-dependent changes in gut microbiota regulate brain plasticity.

neuroscience↗

bioRxiv2020

Exogenous and endogenous HDAC inhibitor effects in Rubinstein-Taybi syndrome models

Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant disorder with specific clinical signs and neurodevelopmental impairment. The two known proteins altered in the majority of RSTS patients are the histone acetylation regulators CBP and p300. For assessing possible ameliorative effects of exogenous and endogenous HDAC inhibitors (HDACi), we exploited in vivo and in vitro RSTS models. First, HDACi effects were tested on Drosophila melanogaster, showing molecular rescue. In the same model, we observed a shift in gut microbiota composition. We then studied HDACi effects in RSTS cell lines compared to healthy donor cells. We observed patients-specific molecular rescue of acetylation defects at subtoxic concentrations. Finally, we assessed commensal gut microbiota composition in a cohort of RSTS patients compared to healthy siblings. Intriguingly, we observed a significant depletion in butyrate-producing bacteria in RSTS patients. In conclusion, this study reports the possibility of modulating acetylation equilibrium by HDACi treatments and the importance of microbiota composition in a chromatinopathy.

genetics↗

bioRxiv2017

Antenatal microbial colonisation of mammalian gut

The widely accepted dogma of intrauterine sterility and initial colonisation of the newborn during birth has been blurred by recent observations of microbial presence in meconium, placenta and amniotic fluid. Given the importance of a maternal-derived in utero infant seeding, it is crucial to exclude potential environmental or procedural contaminations, and to assess foetal colonisation before parturition. To ascertain antenatal microbial colonisation in mammals, we analysed sterilely collected intestinal tissues from rodent foetuses in parallel with experimental controls, and tissues from autoptic human foetuses. Next generation sequencing (NGS) showed the presence of pioneer microbes in both rat and human intestines, as well as in rodent placentas and amniotic fluids. Live microbes were isolated from culture-dependent analyses from homogenized rat foetal intestines.\n\nMicrobial communities showed foetus- and dam-dependent clustering, confirming the high interindividual variability of microbiota even in the antenatal period. Fluorescent in situ hybridisation analysis confirmed the microbes existence in the lumen of the developing gut.\n\nThese findings have vast implications for an emerging field of enhancing the management of healthy pregnancies, and for understanding how the infant microbiome starts and it is thus shaped.

microbiology↗