Project description:The purpose of this study was to detect the expression profile of tsRNA during deep hypothermia circulatory arrest, and to find possible regulatory factors according to the changes in its expression level, in the hope of providing an effective organ protection strategy for this process.Three blood samples were collected from a central veins line into ethylenediaminetetraacetic acid (EDTA) tubes as follows: T1 (before starting circulatory arrest), T2 (15 min after initiation of DHCA), T3 (after declamping the left common carotid artery and before rewarming). A total of 286 commonly expressed tsRNAs were identified in the T1 and T2 groups, 68 tsRNAs specifically expressed in the T1 group, and 44 tsRNAs specifically expressed in the T2 group. A total of 290 commonly expressed tsRNAs were identified in the T2 and T3 groups, 64 tsRNAs specifically expressed in the T2 group, and 43 tsRNAs specifically expressed in the T3 group. Next, four tsRNAs were selected to be verified by qRT-PCR. In summary, this study innovatively proposed the correlation between the deep hypothermic circulatory arrest process and the expression profile of tsRNA, and evaluated the expression level and regulation mode of tsRNA. A preliminary exploration of its potential biological role in the process of deep hypothermic circulatory arrest has been carried out, which can provide a better basis and a more comprehensive explanation for the organ protection mechanism of deep hypothermic circulatory arrest. And in further research, we are expected to achieve targeted protection of organs by overexpressing or inhibiting the corresponding tsRNA.
Project description:The goal of the study was to identify the gene changes that occur in the striatum of neonatal piglets exposed to cardiopulmonary bypass (CPB) with deep hypothermic cardiac arrest (DHCA) then recovered for 6h. To accomplish our goal, mRNA-seq was performed on RNA isolated from neonatal pigs exposed to either DHCA or sham conditions.
Project description:Differential expression profiles and functional prediction of tRNA-derived small RNAs in plasma of patients with aortic dissection during deep hypothermic circulatory arrest
Project description:Hypothermic oxygenated machine perfusion promotes mitophagy flux against hypoxia ischemic injury in donation after circulatory death liver
Project description:In DCD organ donation one of the significant problems for the organ is the inflammatory response due to ischaemia reperfusion injury caused by warm ischaemia prior to retrieval followed by warm reoxygenation upon transplantation. We developed a model where a DCD kidney was retrieved and preserved using hypothermic machine perfusion with cold University of Wisconsin solution with/without the addition of heparinoids low molecular weight heparin and pentosan polysulfate (PPS) followed by warm oxygenated perfusion with modified Krebs-Henseleit buffer to simulate early ischaemia reperfusion injury (IRI). The donor rats consisted of a control group cold perfusion group compared to warm perfusion and groups treated with either low molecular weight heparin or PPS to assess their activity in ameliorating IRI. We used equimolar pooled RNA samples from each group to perform an exploratory microarray experiment Donor kidneys were harvested and preserved by hypothermic machine perfusion with University of Wisconsin (UW) Solution for 3 hours followed by warm oxygenated perfusion with modified Krebs-Henseleit buffer for 30 minutes to simulate transplantation and whole blood ischaemia reperfusion injury. The model was then used to test the anti-inflammatory properties of the glycosaminoglycan heparin and PPS when used as supplements into perfusate solutions. Half of the donor kidney was used to extract RNA using the Tri reagent and stored in RNA Later. The qualitative best three RNAs from each group were quantified by fluorimetry and mixed in an equimolar manner and used for microarray analysis.
Project description:This study aimed to find diagnostic biomarkers for predicting cardiac surgery-associated acute kidney injury in children. We found that the change of exomiRs level in circulatory system occurred in the early stage after cardiac operation, and the changes of hsa-miR-184 and hsa-miR-6766-3p content in circulatory system could predict CSA-AKI well.
Project description:Ischemia/reperfusion injury (IRI) is a hallmark of tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for repair of DCD kidneys. Doxycycline administration has shown protective effects during IRI. Here, we explore the impact of doxycycline on proteolytic degradation mechanisms and the urinary proteome of perfused kidney grafts. Porcine kidneys underwent 30 min of warm ischemia, 24 h of oxygenated HMP (control/doxycycline) and 240 min of ex-vivo reperfusion. A high-efficiency undecanal-based N-termini enrichment workflow (HUNTER) was performed to identify the tissue degradome. In addition, a proteomic analysis was applied on urine samples collected during reperfusion using label-free quantitation (LFQ) mass spectrometry. Hierarchical clustering showed distinctive clustering profiles between urine samples collected at T15 min (metabolism) and T240 min (complement and coagulation). At T10, significantly more degraded proteins were observed in perfusates of the control group. At T240, significantly more degraded proteins were observed in the doxycycline group, indicating that doxycycline alters protein degradation during HMP. In conclusion, doxycycline administration during HMP led to significant proteomic differences including protective effects by attenuating urinary NGAL levels. Ultimately, we unravelled multiple pathways that undergo alterations during machine perfusion that can be targeted to attenuate IRI induced injury.
Project description:We performed deep sequencing of the miRNAs present in ~20 toxicologically relevant tissues in Sprague Dawley rats and used three independent analysis of the data to determine which miRNAs are tissue specific and tissue enriched.
