Venom induced pressure elevation reversible syndrome: a severe pediatric rattlesnake envenomation, evidence for conservative management, and call for naming the syndromeVenom induced pressure elevation reversible syndrome: a severe pediatric rattlesnake envenomation, evidence for conservative management, and call for naming the syndrome

Posted by
  Venom induced pressure elevation reversible syndrome: a severe pediatric rattlesnake envenomation, evidence for conservative management, and call for naming the syndromeVenom induced pressure elevation reversible syndrome: a severe pediatric rattlesnake envenomation, evidence for conservative management, and call for naming the syndrome Abstract Introduction : Rattlesnake envenomation frequently mimics traumatic compartment syndrome, as both are characterized by severe pain, swelling, and elevated compartment pressures. Unlike traumatic compartment syndrome there have been no documented cases of ischemic limb injury after envenomated patients have received antivenom. Furthermore, there is experimental evidence that fasciotomy worsens myonecrosis. This has led medical toxicologists and surgical guidelines to shift from liberally recommending fasciotomy to near universal recommendation of antivenom alone. Despite this, fasciotomies continue to be recommended and performed on rattle...

PIMR, a novel Kunitz-type protease inhibitor from the Macrovipera razii, with dual anticoagulant and anticancer activities

Posted by

 


PIMR, a novel Kunitz-type protease inhibitor from the Macrovipera razii, with dual anticoagulant and anticancer activities

Abstract

Snake venom is a rich source of bioactive peptides with diverse pharmacological effects. Kunitz-type protease inhibitors are one of the multifunctional peptides isolated from the snake venom. The Razi’s viper, Macrovipera razii, is a species endemic to Iran whose venom components are still largely unexplored. In this study, we report the isolation, cloning, and functional characterization of PIMR, a novel Kunitz-type protease inhibitor derived from M. razii venom. The gene encoding PIMR was amplified from venom gland cDNA and then cloned into a prokaryotic expression vector. The PIMR protein consists of 71 residues stabilized by three disulfide bonds, characteristic of the folded Kunitz domain. Recombinant PIMR was expressed in Escherichia coli and purified by affinity chromatography. The anticoagulant activity of PIMR was assessed by clotting time, prothrombin time, and activated partial thromboplastin time assays. The results indicated a dose-dependent anticoagulant activity of the peptide. The PIMR also exhibited anticancer effects against the highly invasive breast cancer cell line, MDA-MB-231, with an IC50 of 33 μg/μl. Docking studies indicated that the RGN motif of PIMR interacts with integrins, suggesting a potential mechanism for inhibiting cancer cell proliferation. Additionally, molecular docking confirmed binding of PIMR to trypsin, supporting its role as a serine protease inhibitor. Our findings establish PIMR as a novel serine protease inhibitor with promising anti-coagulant and anti-cancer properties. PIMR, with its diverse biological functions, represents a potential candidate for drug development and further molecular investigations.
Moshtaghian, P., Ayat, H., Ahadi, A. M., & Oraie, H. (2025). PIMR, a novel Kunitz-type protease inhibitor from the Macrovipera razii, with dual anticoagulant and anticancer activities. Biochimie. https://doi.org/10.1016/j.biochi.2025.11.005