Biology subjects

Machado, V.

Publications and source records attributed to Machado, V..

3 recordsLinked to original sources

bioRxiv2025

Intestinal stem cell marker MEX3A regulates PPARγ expression with functional impact in colorectal carcinogenesis

RNA-binding proteins (RBPs) are major effectors of post-transcriptional regulation. Recently, we described the role of MEX3A in maintaining intestinal stem cell identity and epithelial renewal by repressing the PPAR{gamma} pathway. This work aimed to study MEX3A functional impact in colorectal cancer (CRC). MEX3A and PPAR{gamma} expression profiles were characterized in murine and human models. CRISPR/Cas9-mediated MEX3A knockout was performed in patient-derived CRC tumoroids (PDCTs) and MEX3A RNA targets identified through the HyperTRIBE technique. Apc+/fl;Mex3a+/- mice presented a significant reduction in tumor burden. Apc+/fl;Kras+/G12D;Mex3a+/-mice presented a reduced tumor area, while corresponding tumoroids exhibited reduced growth and enhanced differentiation potential mediated by PPAR{gamma} signalling. MEX3A overexpression (85% of human CRC cases) was inversely correlated with PPAR{gamma} downregulation (72% of cases). Accordingly, MEX3A-depleted PDCTs showed decreased LGR5 expression, accompanied by increased PPAR{gamma} expression and higher sensitivity to 5-Fluorouracil/Oxaliplatin (FOLFOX)-based chemotherapy. The HyperTRIBE results revealed a direct interaction between MEX3A and PPARG transcripts. STATEMENT OF SIGNIFICANCEThese results emphasize that MEX3A plays a crucial role in colorectal carcinogenesis, partially through regulation of the PPARG pathway, mediating tumour development and response to therapy, thus constituting a potential therapeutic target.

cancer biology↗

bioRxiv2021

Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drive rapid and potent immunogenicity capable of single-dose protection

Antibodies from SARS-CoV-2 vaccines may target epitopes which reduce durability or increase the potential for escape from vaccine-induced immunity. Using a novel synthetic vaccinology pipeline, we developed rationally immune focused SARS-CoV-2 Spike-based vaccines. N-linked glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and comprehensive in vitro screening, we incorporated glycans into the Spike Receptor-Binding Domain (RBD) and assessed antigenic profiles. We developed glycan coated RBD immunogens and engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicited potent neutralizing antibodies in guinea pigs, hamsters and multiple mouse models, including human ACE2 and human B cell repertoire transgenics. RBD nanoparticles encoding wild-type and the P.1 SARS-CoV-2 variant induced high levels of cross-neutralizing antibodies. Single, low dose immunization protected against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of novel, potent coronavirus vaccines.

immunology↗

bioRxiv2020

A new approach for quantifying phosphorus requirement in an Amazonian fish using CT-scanning

Phosphorus (P) is an essential mineral for fish growth, as it plays pivotal roles in skeletal development and energy transfer reactions. However, the dietary requirement of this mineral is variable among fish species and the growth stages. Thus, this study aimed to determine the digestible P (dP) requirement for tambaqui in the initial growth stage ({+/-} 17 to 150g) using growth data, mineralization of the whole body, vertebrae and scales, as well as blood chemistry as response parameters. A total of 192 tambaqui juveniles of approximately 17 {+/-} 0.85 g were stocked into a water recirculation system. Fish were assigned to 24 70L-tanks using randomized block design (two floors) with six treatments (1.3, 2.4, 4.8, 6.3, 7.8 and 8.8 g kg-1 dP) and four replicates. Fish were fed six semipurified diets with increasing levels of dP for 90 days. The dietary requirement of P was estimated using regression models (P < 0.05). Duncan and SNK multiple range tests were used when regression models were not fitted. No mortality or apparent signs of P deficiency were observed. All performance variables were improved with increasing levels of dP in the diet. Based on weight gain, the P requirement was 6.3g kg-1 diet while for increased carcass mineral deposition was 6.6g kg-1 diet and for adequate mineralization of vertebrae the requirement was 4.75 g dP kg-1 diet. The blood chemistry parameters were greatly affected by the dietary P level, except for serum calcium. Thus, the dietary dP requirement for tambaqui juveniles in the early stage was 6.3 g kg-1 diet based on growth and bone mineralization.

physiology↗