Biology subjects

Da Silva, P.

Publications and source records attributed to Da Silva, P..

3 recordsLinked to original sources

bioRxiv2026

Intranasal Anti-CD3 Antibody Treatment Attenuates Post-COVID Neuroinflammation and Enhances Hippocampal Neurogenesis and Cognitive Function in Mice

Cognitive impairment is a disabling feature of Long COVID, with data supporting neuroinflammation and maladaptive glial responses as primary drivers. Nasal administration of an anti-CD3 monoclonal antibody (aCD3 mAb) has shown therapeutic benefits in autoimmune and CNS disease models. Using a respiratory-restricted mild SARS-CoV-2 mouse model of Long COVID, we show that nasal anti-CD3 mAb, administered shortly after infection or during chronic neuroinflammation, increased brain FoxP3+ IL-10+ Tregs, reduced microglial and astrocytic gliosis in the white matter and hippocampus, restored neurogenesis, and improved short-term memory. Nasal aCD3 mAb reprogrammed microglia from an antigen-presenting, NF-{kappa}B-driven inflammatory state toward chemokine signaling, phagosome, and TGF {beta}-related regulatory phenotype. Patients with Long COVID with neurological symptoms had lower circulating Treg populations. These findings identify nasal administration of aCD3 mAb as a noninvasive strategy to control neuroinflammation, restore the neurogenic niche, and offer a novel approach to treating cognitive impairment in Long COVID.

immunology↗

bioRxiv2025

Liver FGF21 mediates sex-specific adaptation to juvenile protein malnutrition

Dietary protein sufficiency during childhood is essential for healthy growth and tissue development. Chronic protein deficiency leads to stunting, height-for-age more than two standard deviations below the median, and affects 149 million children under five (https://www.who.int/publications/i/item/9789240073791). Linear growth is governed by the somatotropic axis, wherein pituitary growth hormone (GH) stimulates hepatic insulin-like growth factor 1 (IGF-1) to promote bone elongation1. Although boys are consistently more stunted than girls across populations (ranging from 18% to 45%)2,3, mechanisms underlying this apparent resilience remain unclear. Rodent studies suggest that the protein-to-carbohydrate ratio modulates life-history traits such as metabolism, lifespan, and reproduction, with evidence of sex-dependent sensitivity4,5. Whether such dimorphism reflects coordinated developmental adaptations in response to protein scarcity, particularly in females, has not been fully explored. Here, we show that juvenile dietary protein restriction causes sexually dimorphic adaptations with pronounced stunting in males and delayed reproductive maturation in females. Using liver-specific deletion, we identify fibroblast growth factor 21 (FGF21) as a sex-specific hepatic regulator of female somatic growth and reproductive development, revealing a dimorphic endocrine adaptation to early-life protein scarcity. Our findings position FGF21 as a critical physiological checkpoint coordinating growth and reproductive timing in response to nutritional stress.

physiology↗

bioRxiv2021

Early transcriptomic response of Alnus glutinosa to Frankia alni symbiont, an upregulated nsLTP (non-specific Lipid Transfer Protein) is implicated in early and late stages of symbiosis

Alnus glutinosa response to Frankia alni is driven by several sequential physiological modifications that include calcium spiking, root hair deformation, penetration, induction of primordium, formation and growth of nodule. Here, we have conducted a transcriptomic study to analyse plant responses to Frankia alni at early stages of symbiosis establishment. Forty-two genes were significantly activated by either with a Frankia culture supernatant or with living cells separated from the roots by a dialysis membrane permitted to identify plant genes which expression changes upon early contact with Frankia. Most of these genes encode biological processes, including oxidative stress and response to stimuli. The most upregulated gene is the non-specific lipid transfer protein (nsLTP) encoding gene with a fold change of 141. Physiological experiments showed that nsLTP increases Frankia nitrogen fixation at sub-lethal concentration. Immunohistochemistry experiments conducted at an early infection stage indicated that nsLTP protein is localized at the deformed root hair region after Frankia inoculation and later in nodules, precisely around bacterial vesicles. Taken together, these results suggest that nsLTP acts at early and late stages of symbiosis, probably by increasing nitrogen uptake by Frankia.

plant biology↗