Overexpression of miR-22-3p and miR-29c-3p in CFU-Hill colonies is related to senescence process among children with low birth weight.

BACKGROUND: The current study mainly focused on provide further insights into the association of the miR-22-3p and miR-29c-3p expression in CFU-Hill colonies with birth weight and senescence process in children. METHODS: This cross-sectional study evaluated 61 children (32 boys, 29 girls). The CFU-Hill colonies number was evaluated in vitro by cell culture technique and senescence was detected by ß-galactosidase (SA-ß-Gal) assay. Expression of miR-22-3p and miR-29c-3p isolated from CFU-Hill colonies were detected using quantitative real-time polymerase chain reaction. RESULTS: Birth weight was correlated with both CFU-Hill colonies and %SA-ß-Gal positive staining. Multivariate linear regression analysis revealed that the senescence was a predictor of the lower CFU-Hill colonies number, while only the birth weight was a predictor of senescence of CFU-Hill colonies. Overexpression of miR-22-3p and miR-29c-3p was observed in CFU-Hill colonies isolated from children with low birth weight (LBW). Interestingly, we found a significant correlation between %SA-ß-Gal cells staining positive for both miR-22-3p and miR-29c-3p. CONCLUSION: The LBW is associated with decreased CFU-Hill colonies number and high senescence of these cells. The overexpression of miR-22-3p and miR-29c-3p may be partially responsible for this alteration due to regulation of several pathways related to the senescence process. IMPACT: The study establishes a significant correlation between birth weight and the number of CFU-Hill colonies, suggesting that birth weight could be a predictive biomarker for vascular health in children. Data indicates that cellular senescence is a predictor of reduced CFU-Hill colony numbers. This suggests that the aging process of these cells could be an important factor in understanding the vascular health issues in children with low birth weight. The overexpression of miR-22-3p and miR-29c-3p in children with low birth weight and their correlation with increased cellular senescence highlight these microRNAs as possible molecular mechanisms influencing the aging of CFU-Hill colonies.

The Brazilian Zika virus strain causes birth defects in experimental models.

Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.

Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice.

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.