Biology subjects

Barrera, N. P.

Publications and source records attributed to Barrera, N. P..

3 recordsLinked to original sources

bioRxiv2026

Tocilizumab induces significant changes in longitudinal proteomes of blood serum from patients with severe COVID-19 pneumonia

Coronavirus disease 2019 (COVID-19) shows highly variable clinical outcomes that are not fully explained by age or comorbidities, underscoring the importance of host molecular responses in determining disease severity. Proteomic and multi-omics studies have linked severe COVID-19 to profound dysregulation of immune, inflammatory, and coagulation pathways, and have shown that circulating protein signatures can predict clinical trajectories. Tocilizumab (TCZ), a monoclonal antibody targeting the interleukin-6 receptor (IL-6R), is an established therapy for IL-6-driven inflammatory diseases and can normalize aberrant molecular profiles. Here, we applied longitudinal serum proteomics to patients with severe SARS-CoV-2 pneumonia treated with TCZ to further characterize how IL-6R blockade reshapes the systemic inflammatory milieu. After TCZ administration, several clinical and inflammatory markers, including C-reactive protein (CRP), CCL5 and CXCL10, decreased. Proteomic profiling revealed that TCZ exerts a sustained effect on the serum proteome, with the most pronounced changes emerging 7 days after treatment. These changes were associated with a broad reconfiguration of the proteomic profile toward a pattern resembling a healthy physiological state, characterized by the restoration of key protein abundances to levels comparable to those observed under homeostatic conditions. Collectively, our findings support that TCZ treatment contributes to the normalization of the inflammatory state in severe COVID-19 and represents a viable therapeutic option for managing the acute inflammatory phase of the disease, while also highlighting additional pathways and biomarkers involved in this recovery process.

pharmacology and toxicology↗

bioRxiv2025

Royal Jelly Derived Extracellular Vesicles Modulate Microglial Nanomechanics and Inflammatory Responses

BACKGROUND: Microglia, the brain's resident immune cells, undergo profound mechanical and functional changes upon activation contributing to neuroinflammation, a pathological signature of many neurological diseases. Thus, new anti-inflammatory treatment options are needed that tackle these mechanobiological alterations in microglia, which remain strongly understudied. In this context, extracellular vesicles (EVs) are crucial mediators of intercellular and interkingdom communication, yet their influence on the mechanobiological properties of recipient cells remains largely unknown. Honeybee-derived Royal Jelly EVs (RJEVs) have demonstrated remarkable anti-inflammatory properties, but their impact on microglial cellular nanomechanics and uptake mechanisms remains unclear. RESULTS: In this study, we used a multi-disciplinary approach to analyze the resulting biological and nanomechanical changes following the activation of human microglia and the potential effect of RJEV treatment on these mechanobiological parameters. We observed that LPS treatment was associated with decreased cellular Young's modulus, increased membrane fluidity, and enhanced motility of microglia, indicating a more migratory and pro-inflammatory phenotype. Additionally, LPS exposure altered cellular EV uptake mechanisms by shifting preference from an equilibrium of four mechanisms to the predominance of macropinocytosis and clathrin-dependent endocytosis. Remarkably, RJEV treatment counteracted these mechanobiological changes by, in turn, increasing microglial stiffness, reducing motility, and decreasing secretion of pro-inflammatory cytokines. CONCLUSION: This is the first study to demonstrate that microglial activation state dictates EV uptake mechanisms and to establish a direct link between inflammation, cellular and membrane mechanics, and EV-mediated modulation. Our findings highlight RJEVs as promising candidates for regulating neuroinflammation by targeting microglial mechanobiology as well as opening new strategies for EV-based therapeutics.

neuroscience↗

bioRxiv2022

Nanoscale dynamics of streptococcal adhesion to AGE-modified collagen

The adhesion of initial colonizers such as Streptococcus mutans to collagen is critical for dentinal and root caries progression. One of the most described pathological and aging-associated changes in collagen - including dentinal collagen - is the generation of advanced glycation end-products (AGEs) such as methylglyoxal (MGO)-derived AGEs. Despite previous reports suggesting that AGEs alter bacterial adhesion to collagen, the biophysics driving oral streptococcal attachment to MGO-modified collagen remains largely understudied. Thus, the aim of this work was to unravel the dynamics of the initial adhesion of S. mutans to type-I collagen in the presence and absence of MGO-derived AGEs, by employing bacterial cell force-spectroscopy with atomic force microscopy (AFM). Type-I collagen gels were treated with 10mM MGO to induce AGE formation, which was characterized with microscopy and ELISA. Subsequently, AFM cantilevers were functionalized with living S. mutans UA 159 or S. sanguinis SK 36 cells and probed against collagen surfaces to obtain force-curves displaying bacterial attachment in real-time, from which the adhesion force, number of events, Poisson analysis, and contour and rupture lengths for each individual detachment event were computed. Furthermore, in-silico docking studies between the relevant S. mutans UA 159 collagen-binding protein SpaP and collagen were computed, in the presence and absence of MGO. Overall, results showed that MGO modification increased both the number and adhesion force of single-unbinding events between S. mutans and collagen, without altering the contour or rupture lengths. Both experimental and in-silico simulations suggest that this effect is due to increased specific and non-specific forces and interactions between S. mutans UA 159 and MGO-modified collagen substrates. In summary, these results suggest that collagen alterations due to glycation and AGE formation may play a role in early bacterial adherence to oral tissues, associated with conditions such as aging or chronic hyperglycemia, amongst others.

microbiology↗