The inhibition of eIF5A hypusination by GC7, a preconditioning protocol to prevent brain death-induced renal injuries in a preclinical porcine kidney transplantation model.

The eIF5A hypusination inhibitor GC7 (N1-guanyl-1,7-diaminoheptane) was shown to protect from ischemic injuries. We hypothesized that GC7 could be useful for preconditioning kidneys from donors before transplantation. Using a preclinical porcine brain death (BD) donation model, we carried out in vivo evaluation of GC7 pretreatment (3 mg/kg iv, 5 minutes after BD) at the beginning of the 4h-donor management, after which kidneys were collected and cold-stored (18h in University of Wisconsin solution) and 1 was allotransplanted. Groups were defined as following (n = 6 per group): healthy (CTL), untreated BD (Vehicle), and GC7-treated BD (Vehicle + GC7). At the end of 4h-management, GC7 treatment decreased BD-induced markers, as radical oxygen species markers. In addition, GC7 increased expression of mitochondrial protective peroxisome proliferator-activated receptor-gamma coactivator-1-alpha (PGC1α) and antioxidant proteins (superoxyde-dismutase-2, heme oxygenase-1, nuclear factor [erythroid-derived 2]-like 2 [NRF2], and sirtuins). At the end of cold storage, GC7 treatment induced an increase of NRF2 and PGC1α mRNA and a better mitochondrial integrity/homeostasis with a decrease of dynamin- related protein-1 activation and increase of mitofusin-2. Moreover, GC7 treatment significantly improved kidney outcome during 90 days follow-up after transplantation (fewer creatininemia and fibrosis). Overall, GC7 treatment was shown to be protective for kidneys against BD-induced injuries during donor management and subsequently appeared to preserve antioxidant defenses and mitochondria homeostasis; these protective effects being accompanied by a better transplantation outcome.

Unmatched Virus Preservation Solution may Impede One-Step Reagent for Detection of 2019-nCoV RNA.

BACKGROUND AND METHODS: 2019 Corona Virus Disease (COVID-19) caused by SARS-CoV-2 is still pandemic now. RT-qPCR detection was the most common method for the diagnosis of SARS-CoV-2 infection, facilitated by amounts of nucleic acid testing kits. However, the accuracy of nucleic acid detection is affected by various factors such as specimen collection, specimen preparation, reagents deficiency, and personnel quality. RESULTS: In this study, we found that unmatched virus preservation solution will inhibit N gene and OFR-1ab gene (two independent genes of SARS-CoV-2) amplification in one-step detection reagent. CONCLUSIONS: Despite just being a particular phenomenon we found in our work to fight 2019-nCoV, we concluded that unmatched virus preservation solution may have an inhibitory effect on SARS-CoV-2 nucleic acid detection which may lead to incorrect clinical diagnosis.