Methotrexate might be valuable to fight breast cancer.

Venomous animals are found through a wide taxonomic range including cartilaginous fish such as the freshwater stingray Potamotrygon motoro occurring in South America, which can injure people and cause venom-related symptoms. Ensuring the efficacy of drug development to treat stingray injuries can be assisted by the knowledge of the venom composition. Here we performed a detailed transcriptomic characterization of the venom gland of the South American freshwater stingray Potamotrygon motoro. The transcripts retrieved showed 418 hits to venom components (comparably to 426 and 396 hits in other two Potamotrygon species), with high expression levels of hyaluronidase, cystatin and calglandulin along with hits uniquely found in P. motoro such as DELTA-alicitoxin-Pse1b, Augerpeptide hhe53 and PI-actitoxin-Aeq3a. We also identified undescribed molecules with extremely high expression values with sequence similarity to the SE-cephalotoxin and Rapunzel genes. Comparative analyses showed that despite being closely related, there may be significant variation among the venoms of freshwater stingrays, highlighting the importance of considering elicit care in handling different envenomation cases. Since hyaluronidase represents a major component of fish venom, we have performed phylogenetic and selective pressure analyses of this gene/protein across all fish with the available information. Results indicated an independent recruitment of the hyaluronidase into the stingray venom relative to that of venomous bony fish. The hyaluronidase residues were found to be mostly under negative selection, but 18 sites showed evidence of diversifying positive selection (P < 0.05). Our data provides new insight into stingray venom variation, composition, and selective pressure in hyaluronidase.

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