Biology subjects

Souza, A. d.

Publications and source records attributed to Souza, A. d..

3 recordsLinked to original sources

bioRxiv2026

Biodegradable Intra-arterial Devices for Focal Drug Delivery to Targeted Organs

This study presents the development of biodegradable intra-arterial drug delivery (IADD) devices for the focal treatment of targeted organs. The IADD devices are fabricated using magnesium (Mg) and poly(glycerol sebacate) (PGS), leveraging their biocompatibility and tunable biodegradability, and are loaded with two model drugs, dexamethasone (DEX) or cisplatin (CIS). The IADD devices with helical and linear designs were fabricated for focal drug delivery to targeted organs and characterized for their microstructure and composition using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR). The results confirmed the successful incorporation and stability of the drugs within the device. The IADD devices demonstrated in vitro release of DEX and CIS over 30 days, with drug-dependent and fabrication-dependent release profiles. The IADD devices demonstrated cytocompatibility with endothelial cells and sustained pharmacological activity against glioma cells throughout the in vitro release period. DEX-loaded IADD devices were implanted into the artery upstream of a target organ in rat models. The devices implanted into the renal artery to target the kidney and the carotid artery to target the brain achieved 109-fold and 68-fold improvements, respectively, in organ vs systemic drug levels compared to oral drug administration. Arterial histology and explanted-device analysis provided preliminary evidence of local vascular tolerability and device integrity over the examined implantation period. Overall, these results support IADD devices as a proof-of-concept approach for focal intra-arterial drug delivery to targeted organs, demonstrating substantially elevated target-organ drug levels relative to systemic exposure. HighlightsO_LIIntroduction of a novel intra-arterial drug delivery (IADD) platform C_LIO_LIIADD devices were fabricated from bioresorbable Mg and drug-loaded PGS C_LIO_LIDEX- and CIS-loaded IADD devices were evaluated for in vitro release and bioactivity C_LIO_LIIADD delivery achieved marked DEX enrichment in the kidney and brain C_LIO_LIPost-implantation studies support preliminary vascular safety C_LI

bioengineering↗

bioRxiv2025

Heme-NO dilates arteries via mobilization of NO moieties from a vascular intracellular NO store

Nitrosyl heme (heme-NO) has recently emerged as a surrogate signaling entity for nitric oxide (NO). However, questions remain about how heme-NO signals across the cell membrane. Herein, we test the hypothesis that heme-NO signals as a nitrodilator that vasodilates by mobilizing NO moiety from a nitrodilator-activated intracellular NO store (NANOS) in the vasculature. We identify a novel mechanism for glutathione-catalyzed formation of a model compound, alb-heme-NO, and determine glutathione (GSH) as a ligand in its structure. Heme-NO complexes with plasma proteins in blood and, as such, it is impermeable to red blood cells or the vascular wall. Alb-heme-NO-mediated vasodilation, both in vitro and in vivo, is attenuated by prior depletion of the NANOS and potentiated by NANOS supplementation. Incubation with alb-heme-NO induces efflux of NO moieties from arteries. Additionally, the role of nitrosyl hemoglobin (HbNO) in mediating NO bioactivity export from erythrocytes is challenged. In conclusion, heme-NO functions as an extracellular nitrodilator via activation of the intracellular NANOS.

physiology↗

bioRxiv2025

Estimating the replicability of Brazilian biomedical science

Concerns over the replicability and reproducibility of published research have grown in many research fields, but empirical data to inform policies are still scarce. Biomedical research in Brazil expanded rapidly over the last three decades, with no systematic assessment of the replicability of its findings. With this in mind, we set up the Brazilian Reproducibility Initiative, a multicenter replication of published experiments from Brazilian science using three common experimental methods: the MTT assay, the reverse transcription polymerase chain reaction (RT-PCR) and the elevated plus maze (EPM). A total of 56 laboratories performed 143 replications of 56 experiments; of these, 90 replications of 45 experiments were considered valid by an independent committee. Replication rates for these experiments varied between 20 and 44% according to five predefined criteria. In median terms, ratios between group means were 58% lower in replications than in original experiments, while coefficients of variation were 82% higher. Effect size decrease was smaller for MTT experiments, original results with less variability and those considered more challenging to replicate, while t values for replications were positively correlated with researcher predictions about replicability, and negatively correlated with the rate of publications by the original articles last author. Deviations from preregistered protocols were very common in replications, most frequently due to reasons inherent to the experimental model or related to infrastructure and logistics. Our results highlight factors that limit the replicability of results published by researchers in Brazil and suggest ways by which this scenario can be improved.

scientific communication and education↗