Small molecule inhibitor binds to NLRP3 and prevents inflammasome activation.

Despite recent advances in the mechanism of oxidized DNA activating NLRP3, the molecular mechanism and consequence of oxidized DNA associating with NLRP3 remains unknown. Cytosolic NLRP3 binds oxidized DNA which has been released from the mitochondria, which subsequently triggers inflammasome activation. Human glycosylase (hOGG1) repairs oxidized DNA damage which inhibits inflammasome activation. The fold of NLRP3 pyrin domain contains amino acids and a protein fold similar to hOGG1. Amino acids that enable hOGG1 to bind and cleave oxidized DNA are conserved in NLRP3. We found NLRP3 could bind and cleave oxidized guanine within mitochondrial DNA. The binding of oxidized DNA to NLRP3 was prevented by small molecule drugs which also inhibit hOGG1. These same drugs also inhibited inflammasome activation. Elucidating this mechanism will enable design of drug memetics that treat inflammasome pathologies, illustrated herein by NLRP3 pyrin domain inhibitors which suppressed interleukin-1ß (IL-1ß) production in macrophages. One-Sentence Summary: NLRP3 cleaves oxidized DNA and small molecule drug binding inhibits inflammasome activation.

Preservation of internal iliac artery flow during endovascular aortic aneurysm repair in a patient with bilateral absence of common iliac artery.

Bilateral absence of the common iliac artery is an extremely rare congenital vascular malformation in which the distal aorta divides directly into two external iliac arteries and two internal iliac arteries. In the case of the presence of this vascular malformation in association with an aortic aneurysm, preservation of the internal iliac artery flow during endovascular aortic repair represents a technical challenge. We have reported a case in which the bilateral absence of the common iliac artery associated with an infrarenal abdominal aortic aneurysm was successfully treated by endovascular aortic repair using commercially available iliac branched devices to maintain pelvic perfusion.

Rigor mortis development and effects of filleting conditions on the quality of Tra catfish (Pangasius hypophthalmus) fillets.

South-East Asian countries produce several million tons annually of Tra catfish (Pangasius hypophthalmus) fillets for export and domestic consumption. However, the processing procedure has not yet been investigated. This study was carried out to analyze the rigor mortis development of the fish and to evaluate the effects of filleting conditions on the quality of the fillets. Compared to pre-rigor fillet processing, post-rigor fillet processing resulted in higher fillet mass yield, less fillet length contraction and reduced exudation loss during chilled storage for both fillets before freezing and fillets after freezing and thawing. The post-rigor fillet processing led to significantly less drip loss after thawing. For fresh fish fillets, pre-rigor processing led to lower cooking loss compared to post-rigor processing. For frozen and thawed fish fillets there was no significant difference in those two parameters. The present research serves as a foundation for further investigations on the modification of processing practices for better fillet quality.