Project description:Ischemia reperfusion injury (IRI) in organ transplantation remains a significant problem with limited alternative therapeutic options. Organs that undergo significant damage during IRI, particularly those enduring long warm ischemia times, undergo significant delayed graft function (DGF) after reperfusion and tend to have greater complications long term with the onset of chronic rejection. The gas molecule carbon monoxide (CO) has emerged as an agent that can suppress IRI in rodent models of solid organ transplantation. Since the use of CO is a potential therapeutic modality in humans, we tested if CO can prevent DGF in a pig model of kidney transplantation Keywords: stress response, treatment response 18 Samples from pig kidneys, two naïve controls, two timepoints, two conditions, 4 replicates
Project description:Ischemia reperfusion injury (IRI) in organ transplantation remains a significant problem with limited alternative therapeutic options. Organs that undergo significant damage during IRI, particularly those enduring long warm ischemia times, undergo significant delayed graft function (DGF) after reperfusion and tend to have greater complications long term with the onset of chronic rejection. The gas molecule carbon monoxide (CO) has emerged as an agent that can suppress IRI in rodent models of solid organ transplantation. Since the use of CO is a potential therapeutic modality in humans, we tested if CO can prevent DGF in a pig model of kidney transplantation Keywords: stress response, treatment response
Project description:INTRODUCTION Ischemia and reperfusion injury (IRI)-elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest 1. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery 1. IRI, one of the biggest challenges for organ transplantation, continues to be a vital source of morbidity among recipients, especially in liver transplantation 2. With the enlarging shortage of available donor livers, the increased use of extended criteria donor grafts further increases IRI, adversely affecting both short-term and long-term outcomes of graft and patient survival 3. Numerous studies have investigated the benefits of pharmacological, heat shock, and ischemic preconditioning interventions aimed at decreasing liver IRI 4. However, the benefit was limited. Our center has been making great effort in conquering IRI and have developed a novel surgical technique called ischemia-free liver transplantation 5. It is an ultimate method to overcome IRI in liver transplantation, but there is still a long way to popularize it. As a result, it is still of great significance to study IRI and identify the core genes in the process and the underlying mechanism. Comprehensive bioinformatics analysis has been increasingly important as a method to study various pathological and physiological condition 6. By enrolling multiple omics or combining different types of omics, comprehensive bioinformatics analysis was able to recognize key factors that could have potentially pathogenic impact such as gene expression, protein function, and downstream pathways. With the rapid development of high-throughput sequencing technologies, several transcriptomic datasets on IRI of liver transplantation have become available in the Gene Expression Omnibus (GEO) database. Herein, we recruited 3 GEO datasets to conduct comprehensive analysis with the GEO dataset from our center. Moreover, we performed the first proteome of liver tissues to study liver IRI. Then the transcriptome and proteome were used for combined analysis to reveal key factors in liver IRI.
Project description:Primary graft dysfunction (PGD), which is caused primarily by ischemia–reperfusion injury (IRI), is a major obstacle in lung transplantation. Here, we developed an orthotopic, single-lung transplant pig model to simulate prolonged cold IRI. After 24 hours of cold ischemia and 8 hours of warm reperfusion, the transplanted lung exhibited severe allograft injury. Subsequent single-cell RNA sequencing (scRNA-seq) revealed significant changes in alveolar macrophages after IRI, with prominently enriched ferroptosis pathways. Transmission electron microscopy (TEM) confirmed characteristic ferroptosis changes in lung macrophages, and decreased GPX4 expression in macrophages indicated increased susceptibility to ferroptosis. Overall, our pig orthotopic left lung transplant model effectively simulates IRI after transplantation, which offers a valuable platform for more detailed investigations of early reperfusion injury to pulmonary grafts. Moreover, we preliminarily demonstrated the importance of macrophage ferroptosis in IRI, suggesting that inhibiting macrophage ferroptosis may be a promising therapeutic strategy for lung IRI.
Project description:Ischemia-reperfusion injury (IRI) is a major cause of morbidity and mortality following conventional lung transplantation and warm ischemia may limit success of transplanting lungs from non-heart-beating donors. We sought to determine alterations in gene expression in rat lung tissue subjected to warm ischemia in vivo followed by reperfusion. Keywords: time course
Project description:Ischemia-reperfusion injury (IRI) is a well-known model for acute kidney injury (AKI).
We applied proteomic analysis to detect membrane proteins from IRI mouse kidneys. The analysis set are composed of negative control (sham operation), samples of 4-hour after IRI, and samples of 8-hour IRI.
Project description:During kidney transplantation, ischemia reperfusion injury (IRI) is inevitable and leads to oxidative stress and inflammation. We investigated the role of macronutrients in the effects of dietary restriction on both a phenotypical and transcriptional level, thereby comparing protective and nonprotective diets in search for pathways and regulators involved in the protection against IRI.
Project description:Long noncoding RNA profile in the liver after ischemia-reperfusion injury (IRI). In the study presented here, we mixed the three mouse livers after IRI and identified the genome-wide expression level of lncRNAs.
Project description:Long noncoding RNA profile in the mouse plasma after ischemia-reperfusion injury (IRI). In the study presented here, we mixed the plasma from three mouse after IRI and identified the genome-wide expression level of lncRNAs.
Project description:Hypothermic oxygenated machine perfusion (HOPE) is an organ preservation strategy shown to reduce ischemia-reperfusion-injury (IRI)-related complications following liver transplantation this remains to be evaluated in humans. Analysis of liver tissue transcriptome at reperfusion revealed an effect of HOPE on the reactive oxygen species pathway. Two weeks post transplantation, HOPE recipients exhibited increased circulating CD4+FOXP3+CD127lo regulatory T cells (Tregs) (p<0.01), which corresponded to a higher frequency of donor specific Tregs (p<0.01) and was followed by reduced alloreactivity index of CD8+ T cells 3 months post-transplant. Our study provides novel mechanistic insight into the capacity of HOPE to influence liver IRI and to modulate effector and regulatory donor-specific Tcell responses post-transplantation. These findings, which confirm observations made in animal models, help explain the decreased rejection rates reported in patients receiving HOPE-treated allografts.