Biology subjects

Andrade, A. C.

Publications and source records attributed to Andrade, A. C..

3 recordsLinked to original sources

bioRxiv2025

Piezo1 activation increases the release of therapeutic extracellular vesicles after mechanical stimulation in bioreactors

Enhancing protocols and methods for producing therapeutic extracellular vesicles (EVs) in bioreactors is crucial to achieve scalable production while ensuring both quality and quantity. Studies have shown that mechanical stress can promote EV release, although the underlying mechanisms remain largely unclear. Here we investigated which mechanisms are responsible for the increase of EV production under shear stress. EVs were produced from adipose tissue-derived stromal cells (ASCs), also described as mesenchymal stromal cells (MSCs) that can support the regeneration of injured tissues via several paracrine factors. The cultures were treated with GsMTx4, an inhibitor which blocks the Piezo1 ion channels, or with YODA1, its agonist, to assess if mechanical or shear forces pathways are involved in enhancing the EV release. EVs were quantified and characterized after high shear (HS) stimulation compared with no shear stress stimulation (3D) and standard cultures methods (2D). These experiments showed that, after mechanical stimulation by shear stress, EV production increased in bioreactors and this effect was blocked by the inhibition of Piezo1 ion channels with GsMTx4 (88%) with no impact on cell viability. Consistently, the agonist YODA1 increased the EV production (149%). The implications of these findings are significant, especially for regenerative medicine and cellular therapies, where the efficient production of high-quality EVs is crucial. By understanding turbulence-induced shear stress and the natural mechanotransductive pathways within cells, it may be possible to optimize the production of therapeutic EVs, paving the way for more effective treatments in the future.

cell biology↗

bioRxiv2024

Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice

The global impact of the COVID-19 pandemic has been unprecedented, and presently, the world is facing a new challenge known as Post-COVID syndrome (PCS). Current estimates suggest that more than 65 million people are grappling with PCS, encompassing several manifestations, including pulmonary, musculoskeletal, metabolic, and neuropsychiatric sequelae (cognitive and behavioral). The mechanisms underlying PCS remain unclear. The present study aimed to: (i) comprehensively characterize the acute effects of pulmonary inoculation of the betacoronavirus MHV-A59 in immunocompetent mice at clinical, cellular, and molecular levels; (ii) examine potential acute and long-term pulmonary, musculoskeletal, and neuropsychiatric sequelae induced by the betacoronavirus MHV-A59; and to (iii) assess sex-specific differences. Male and female C57Bl/6 mice were initially inoculated with varying viral titers (3x103 to 3x105 PFU/30 L) of the betacoronavirus MHV-A59 via the intranasal route to define the highest inoculum capable of inducing disease without causing mortality. Further experiments were conducted with the 3x104 PFU inoculum. Mice exhibited an altered neutrophil/lymphocyte ratio in the blood in the 2nd and 5th day post-infection (dpi). Marked lung lesions were characterized by hyperplasia of the alveolar walls, infiltration of polymorphonuclear leukocytes (PMN) and mononuclear leukocytes, hemorrhage, increased concentrations of CCL2, CCL3, CCL5, and CXCL1 chemokines, as well as high viral titers until the 5th dpi. While these lung inflammatory signs resolved, other manifestations were observed up to the 60 dpi, including mild brain lesions with gliosis and hyperemic blood vessels, neuromuscular dysfunctions, anhedonic-like behavior, deficits in spatial working memory, and short-term aversive memory. These musculoskeletal and neuropsychiatric complications were exclusive to female mice and were prevented after ovariectomy. In summary, our study describes for the first time a novel sex-dependent model of PCS focused on neuropsychiatric and musculoskeletal disorders. This model provides a unique platform for future investigations regarding the effects of acute therapeutic interventions on the long-term sequelae unleashed by betacoronavirus infection.

neuroscience↗

bioRxiv2019

Linkage disequilibrium and haplotype block patterns in popcorn populations

Linkage disequilibrium (LD) analysis provides information on evolutionary aspects of the populations and allows selecting populations and single nucleotide polymorphisms (SNPs) for association studies. Recently, haplotype blocks have been used to increase the power of quantitative trait loci detection in genome-wide association studies and the prediction accuracy with genomic selection. The objectives of this study were to compare the degree of LD, the LD decay, the LD decay extent, and the number and length of haplotype blocks in the populations and to elaborate the first LD map for maize, for elucidating if the maize chromosomes also had a pattern of interspaced regions of high and low rates of recombination. We used a biparental temperate population, a tropical synthetic, and a tropical breeding population, genotyped for approximately 75,000 SNPs. The level of LD expressed by the r2 values is surprisingly low (0.02, 0.04, and 0.04), but comparable to some non-isolated human populations. The general evidence is that the synthetic is the population with higher LD. It is not expected a significant advantage of haplotype-based association study and along generations genomic selection due to the reduced number of SNPs in the haplotype blocks (2 to 3). The results concerning LD decay (rapid decay after 5-10 kb) and LD decay extent (along up to 300 kb) are in the range observed with maize inbred line panels. Our most important result is that maize chromosomes had a pattern of regions of extensive LD interspaced with regions of low LD. However, our simple simulated LD map provides evidence that this pattern can reflect regions with differences of allele frequencies and LD level (expressed by D) and not regions with high and low rates of recombination.

genetics↗