Biomedical subjects

Alfredo Cabrera-Orefice

Publications and source records attributed to Alfredo Cabrera-Orefice.

2 recordsLinked to original sources

PubMed2025

Venomics of the Arabian saw-scaled viper (Echis coloratus) through transcriptome-guided proteomics and in vitro functional profiling.

The Arabian saw-scaled viper (Echis coloratus) is among the snakes of highest medical relevance in the Middle East and North Africa. However, to date, its venom has been investigated in a very limited number of studies, and much remains unknown regarding its compositional and functional properties. By integrating proteotranscriptomics with bioactivity profiling, we present a comprehensive transcriptome-level catalogue of E. coloratus venom components and their associated biological activities. Our analysis identified 183 venom components belonging to 17 distinct protein families. Relative toxin abundances revealed that 92% of the venom proteome is composed of C-type lectin and C-type lectin-related protein (CTL), L-amino acid oxidase (LAAO), phospholipase A2 (PLA2), snake venom serine protease (SVSP), and snake venom metalloproteinase (SVMP), with CTL and PLA2 alone accounting for 73% of the total composition. Bioassays targeting key aspects of viperid envenomation demonstrated potent protease and PLA2 activity in a concentration-dependent manner. In contrast, Factor Xa-like, plasmin-like, and haemolytic activities were negligible. Marked cytotoxicity was observed at the highest concentration tested (i.e., 25 μg/ml) in the mammalian cell lines MDCK II and Calu-3, whereas cytotoxic effects were minimal at lower concentrations. These findings highlight the complexity and potency of E. coloratus venom, and provide a valuable foundation for improving our understanding of envenomation caused by this species.

Animals↗

PubMed2025

Synergistic targeting of cancer cells through simultaneous inhibition of key metabolic enzymes.

As cancer cell specific rewiring of metabolic networks creates potential therapeutic opportunities, we conducted a synthetic lethal screen utilizing inhibitors of metabolic pathways. Simultaneous administration of (R)-GNE-140 and BMS-986205 (Linrodostat) preferentially halted proliferation of ovarian cancer cells, but not of their non-oncogenically transformed progenitor cells. While (R)-GNE-140 inhibits lactate dehydrogenase (LDH)A/B and thus effective glycolysis, BMS-986205, in addition to its known inhibitory activity on Indoleamine 2,3-dioxygenase (IDO1), also restricts oxidative phosphorylation (OXPHOS), as revealed here. BMS-986205, which is being tested in multiple Phase III clinical trials, inhibits the ubiquinone reduction site of respiratory complex I and thus compromises mitochondrial ATP production. The energetic catastrophe caused by simultaneous interference with glycolysis and OXPHOS resulted in either cell death or the induction of senescence in tumor cells, with the latter being eliminated by senolytics. The frequent synergy observed with combined inhibitor treatment was comprehensively confirmed through testing on tumor cell lines from the DepMap panel and on human colorectal cancer organoids. These experiments revealed highly synergistic activity of the compounds in a third of the tested tumor cell lines, correlating with alterations in genes with known roles in metabolic regulation and demonstrating the therapeutic potential of metabolic intervention.

Humans↗