Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypothermic oxygenated perfusion (HOPE) is a relatively new dynamic preservation procedure that has not been widely implemented in liver transplantation despite its advantages. Improved graft protection is one such advantage offered by HOPE and has been attributed to multiple mechanisms, one of which may be the modulation of the thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) inflammasome pathway. The TXNIP/NLRP3 inflammasome pathway plays a critical role in sterile inflammation under oxidative stress as a result of ischemia/reperfusion injury (IRI). In the current study, we aimed to investigate the graft protection offered by HOPE and its impact on the TXNIP/NLRP3 inflammasome pathway. To simulate conditions of donation after cardiac death (DCD) liver transplantation, rat livers were exposed to 30 min of warm ischemia after cardiac arrest. Livers were then preserved under cold storage (CS) or with HOPE for 3 h. Livers were then subjected to 1 h of isolated reperfusion. Liver injuries were assessed on the isolated perfusion rat liver model system before and after reperfusion. Compared with the CS group, the HOPE group had a significant reduction in liver injury and improvement in liver function. Our findings also revealed that reperfusion injury induced liver damage and activated the TXNIP/NLRP3 inflammasome pathway in DCD rat livers. Pretreatment of DCD rat livers with HOPE inhibited the TXNIP/NLRP3 inflammasome pathway and attenuated liver IRI. Attenuation of oxidative stress as a result of HOPE led to the down-regulation of the TXNIP/NLRP3 inflammasome pathway and thus offered superior protection compared with the traditional CS method of organ preservation.-He, W., Ye, S., Zeng, C., Xue, S., Hu, X., Zhang, X., Gao, S., Xiong, Y., He, X., Vivalda, S., Li, L., Wang, Y., Ye, Q. Hypothermic oxygenated perfusion (HOPE) attenuates ischemia/reperfusion injury in the liver through inhibition of the TXNIP/NLRP3 inflammasome pathway in a rat model of donation after cardiac death.
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PMID:Hypothermic oxygenated perfusion (HOPE) attenuates ischemia/reperfusion injury in the liver through inhibition of the TXNIP/NLRP3 inflammasome pathway in a rat model of donation after cardiac death. 2987 Jun 80

Thioredoxin plays an essential role in bacterial antioxidant machinery and virulence; however, its regulatory actions in the host are less well understood. Reduced human Trx activates transient receptor potential canonical 5 (TRPC5) in inflammation, but there is no evidence of whether these receptors mediate bacterial thioredoxin effects in the host. Importantly, TRPC5 can form functional complexes with other subunits such as TRPC4. Herein, E. coli-derived thioredoxin induced mortality in lipopolysaccharide- (LPS-) injected mice, accompanied by reduction of leukocyte accumulation, regulation of cytokine release into the peritoneum, and impairment of peritoneal macrophage-mediated phagocytosis. Dual TRPC4/TRPC5 blockade by ML204 increased mortality and hypothermia in thioredoxin-treated LPS mice but preserved macrophage's ability to phagocytose. TRPC5 deletion did not alter body temperature but promoted additional accumulation of peritoneal leukocytes and inflammatory mediator release in thioredoxin-administered LPS mice. Thioredoxin diminished macrophage-mediated phagocytosis in wild-type but not TRPC5 knockout animals. TRPC5 ablation did not affect LPS-induced responses. However, ML204 caused mortality associated with exacerbated hypothermia and decreased peritoneal leukocyte numbers and cytokines in LPS-injected mice. These results suggest that bacterial thioredoxin effects under LPS stimuli are mediated by TRPC4 and TRPC5, shedding light on the additional mechanisms of bacterial virulence and on the pathophysiological roles of these receptors.
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PMID:Transient Receptor Potential Canonical Channels 4 and 5 Mediate Escherichia coli-Derived Thioredoxin Effects in Lipopolysaccharide-Injected Mice. 2998 57