Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA112657 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Because of inherent differences between deceased donor (DD) and living donor (LD) liver grafts, we hypothesize that the molecular signatures will be unique, correlating with specific biologic pathways and clinical patterns. Following reperfusion, 579 genes in DD grafts and 1324 genes in LDs were differentially expressed (p<0.005). Many up-regulated LD genes were related to regeneration, biosynthesis and cell cycle, and a large number of down-regulated genes were linked to hepatic metabolism and energy pathways correlating with post-transplant clinical laboratory findings. There was significant up-regulation of inflammatory/immune genes in both DD and LD, each with a distinct pattern. Gene expression patterns of select genes associated with inflammation and regeneration in LD and DD grafts correlated with protein expression. Unique patterns of early gene expression are seen in LD and DD liver grafts, correlating with protein expression and clinical results, demonstrating distinct inflammatory profiles and significant down-regulation of metabolic pathways in LD grafts. Keywords: liver transplantation, live donor transplantation, liver regeneration, microarrays, mRNA expression, reperfusion injury
2009-06-11 | GSE12720 | GEO
Project description:Because of inherent differences between deceased donor (DD) and living donor (LD) liver grafts, we hypothesize that the molecular signatures will be unique, correlating with specific biologic pathways and clinical patterns. Following reperfusion, 579 genes in DD grafts and 1324 genes in LDs were differentially expressed (p<0.005). Many up-regulated LD genes were related to regeneration, biosynthesis and cell cycle, and a large number of down-regulated genes were linked to hepatic metabolism and energy pathways correlating with post-transplant clinical laboratory findings. There was significant up-regulation of inflammatory/immune genes in both DD and LD, each with a distinct pattern. Gene expression patterns of select genes associated with inflammation and regeneration in LD and DD grafts correlated with protein expression. Unique patterns of early gene expression are seen in LD and DD liver grafts, correlating with protein expression and clinical results, demonstrating distinct inflammatory profiles and significant down-regulation of metabolic pathways in LD grafts. Experiment Overall Design: Microarray profiles of 63 biopsies in 13 DD and 8 LD liver grafts done at serial time points (procurement - No Manipulation, backbench - Cold Preservation, and 1-hour post-reperfusion - Post reperfusion) were compared between groups using class comparisons, network and biological function analyses. Specific genes were validated by quantitative PCR and immunopathology. Clinical findings were also compared.
2009-06-23 | E-GEOD-12720 | biostudies-arrayexpress
Project description:Deceased kidney donation after brain death (DBD) is the main source of transplants, yet these grafts yield inferior transplant outcomes when compared to living donation. In brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys that adversely impacts the quality of grafts. Here, we hypothesized that proteolytic processes in DBD kidneys might lead to podocyte damage with subsequent development of post-transplant dysfunction. Using protein topography and migration analysis platform (PROTOMAP), we mapped degradation profiles of cytoskeletal proteins in DBD kidneys. Cytoskeletal proteolytic degradation was further studied by Immunoblotting on a separate cohort of deceased and living donor kidney biopsies. To investigate potential mechanism of kidney cytoskeletal protein degradation, in-vitro human podocytes and ex-vivo precision-cut human kidney slices were employed. We found novel proteolytic profiles of key podocyte cytoskeletal proteins in donor kidneys associated with suboptimal posttransplant function. These were unique to brain-death and were not observed in circulatory-death or living-donor kidneys. Talin-specific protein degradation in DBD kidneys indicated Calpain-1 activation may have a key role in proteolytic processes observed in the dysfunctional kidneys. Investigation of the underlying mechanism suggests that Transforming-Growth Factor-β (TGFβ) induces Calpain-1 activation, leading to brain-death specific podocyte degradation patterns and dysregulation of actin cytoskeleton; events that were prevented, in-vitro, by Calpain inhibition. Conclusion Our data demonstrate that podocyte protein degradation impacts the quality of DBD kidneys, propose a role of TGFβ mediated Calpain-1 proteolytic processing of cytoskeletal Talin-1, suggesting therapeutic opportunities to prevent kidney dysfunction.
2022-08-12 | PXD022074 | Pride
Project description:The study aims to evaluate the efficacy of liver transplantation in the context of non-resectable colorectal liver metastasis. The primary endpoint is the overall survival in this group of patients while the secondary endpoint is the disease-free survival.
Patients included in this protocol will be evaluated either for whole or partial liver transplantation from deceased or living donors.
Type of different transplantations proposed are as follows:
1. Whole liver graft or partial liver (split) from a deceased donor
2. Partial liver graft retrieved from a deceased donor and orthotopically implanted after having performed a left hepatectomy in the recipient.
3. Partial liver graft retrieved from a deceased donor and heterotopically implanted if total hepatectomy can not be performed.
4. Partial liver graft retrieved from a living donor and orthotopically implanted after having performed total hepatectomy.
5. Partial liver graft retrieved from a living donor and orthotopically implanted after having after having performed a left hepatectomy in the recipient.
6. Partial liver graft retrieved from a living donor and heterotopically implanted if total hepatectomy can not be performed.
In cases 2-3-5-6 total hepatectomy of native liver can be secondarily performed after having achieved a proper graft hypertrophy in order to avoid a small for size syndrome
| 2400483 | ecrin-mdr-crc
Project description:Background: Strategies to improve long term renal allograft survival have been directed to recipient dependent mechanisms of renal allograft injury. In contrast, no such efforts have been made to optimize organ quality in the donor. In order to get insight into the deleterious gene pathways expressed at different time points during deceased kidney transplantation, transcriptomics was performed on kidney biopsies from a large cohort of deceased kidney transplants. Methods: A total of 554 kidney biopsies were taken from living and deceased donor kidneys at donation, after cold ischemia and after reperfusion. Transcriptomics by means of whole genome micro-array analyses followed by functional pathway analyses was performed. Results: Oxidative stress and complement- and coagulation pathways were uncovered as potential pathways for intervention in deceased donors. No genes were found to be differentially expressed between donation and cold ischemia. After reperfusion, pathways related to oxidative stress, NOD-like signalling, MAPK, cytokine-cytokine receptor, complement- and-coagulation and chemokines were enriched in kidneys from deceased organ donors. Pathways related to prolonged and worsening deprivation of oxygen were associated with delayed graft function of DCD grafts. Conclusions: The present study reveals oxidative stress and enrichment of complement and coagulation pathways in deceased donor kidneys. Future intervention therapies to optimize donor organ quality and prolong allograft survival should target oxidative stress and innate immune activation in the donor.
2015-04-02 | GSE43974 | GEO
Project description:Ischemia-reperfusion injury during liver transplantation is responsible for early allograft dysfunction (EAD) and failure, both of which are associated with a high risk of morbidity and mortality in the recipient. The purpose of this study was to study major transcriptional alterations in livers procured from different types of human liver donors in order to identify genetic profiles predictive of post-implantation function. We have analyzed samples form living donors (LD), donors after cardiac death (DCD), donors after brain death, with subsequent post-implantation EAD in the recipient (DBD-EAD); and donors after brain death without EAD (DBD). Two samples were obtained from each donor: sample A was taken immediately before cold perfusion (baseline) and sample B 2h after portal reperfusion. We identified clear differences in gene expression patterns according to donor source. Both samples A and B from DBD-EAD and DCD demonstrated over-expression of pro-apoptotic and inflammatory transcripts. However, in DBD and LD, expression of these genes was low at baseline and rose only after reperfusion. DBD and LD demonstrated the greatest increase in overall genetic expression after reperfusion when sample B was contrasted with A, indicating less baseline graft injury in these two groups. Grafts from LD were characterized by activation of transcripts related to anti-ischemic and regenerative processes and fewer pro-inflammatory gene transcripts. This transcriptional events occurring in liver allografts could allow for the prediction of post-transplant function. Pro-inflammatory and ischemic transcriptional changes in the grafts are directly related to donor type and may be useful targets for the development of future therapeutic strategies. The complete database comprised the expression for samples taken from 33 liver grafts. Sample A was taken immediately before cold perfusion (baseline) and sample B 2 h after portal reperfusion. Donors were from one of four groups: living (LD); after cardiac death (DCD); after brain death, with subsequent post-implantation EAD in the recipient (DBD-EAD); and after brain death without EAD (DBD). RNA was extracted from the 66 samples and analyzed using Illumina Beadarray technology. A group of 3 samples from healthy volunteers and 3 samples form LD taken at the start of surgery are included as controls or reference samples. This dataset is part of the TransQST collection.
2013-07-01 | E-GEOD-23649 | biostudies-arrayexpress
Project description:The fate of transplanted kidneys is substantially influenced by the graft quality as transplantation of kidneys from elderly and expanded criteria deceased donors (ECD) is associated with higher occurrence of delayed graft function, rejection and inferior long term outcome. Little is known about early molecular fingerprints of these events in different donor categories. Borderline changes represent the most frequent histological finding early after kidney transplantation. Therefore, transcriptomic profiles of early case biopsies diagnosed as borderline changes were studied in ECD, standard criteria deceased donors (SCD) and living donor (LD) kidney transplantation using RNA microarray (Agilent SurePrintG3). The increased transcripts typical for ECD as compared to LD (n=437) showed enrichment of extracellular matrix (ECM) -receptor interaction (p=0.004) and complement and coagulation pathways (p=0.004) and GO terms related to platelet activation, blood coagulation, regulation of cell cycle, acute inflammatory response, wound healing or defense response (p<0.001). Gene annotation analysis of transcripts with increased expression in ECD grafts compared to SCD (n=244) showed the highest enrichment of inflammatory response (p=0.013), response to wounding (p=0.001) and defense response (p=0.005) and ECM-receptor interaction pathway (p=0.043). Comparative gene expression overlaps of ECD, SCD and LD using Venn’s diagrams found 62 up- and 16 down-regulated genes in ECD compared to both LD and SCD. Shared increased transcripts in ECD vs. both SCD and LD included, thrombospondin 2 (THBS2), angiopoietin-like 4 (ANGPTL4), collagens (COL6A3, COL1A1), chemokines CCL13 or interleukin IL11 and most significant down-regulated transcripts included proline rich 35 (PRR35) and fibroblast growth factor 9 (FGF9). Transcriptomic profile of higher inflammation and extracellular matrix remodeling in early borderline changes in the ECD kidney allografts suggest mechanisms how ischemia/reperfusion injury aggravates alloimmune response in the presence of chronic vascular changes.
2019-07-18 | GSE134386 | GEO
Project description:Ischemia-reperfusion injury during liver transplantation is responsible for early allograft dysfunction (EAD) and failure, both of which are associated with a high risk of morbidity and mortality in the recipient. The purpose of this study was to study major transcriptional alterations in livers procured from different types of human liver donors in order to identify genetic profiles predictive of post-implantation function. We have analyzed samples form living donors (LD), donors after cardiac death (DCD), donors after brain death, with subsequent post-implantation EAD in the recipient (DBD-EAD); and donors after brain death without EAD (DBD). Two samples were obtained from each donor: sample A was taken immediately before cold perfusion (baseline) and sample B 2h after portal reperfusion. We identified clear differences in gene expression patterns according to donor source. Both samples A and B from DBD-EAD and DCD demonstrated over-expression of pro-apoptotic and inflammatory transcripts. However, in DBD and LD, expression of these genes was low at baseline and rose only after reperfusion. DBD and LD demonstrated the greatest increase in overall genetic expression after reperfusion when sample B was contrasted with A, indicating less baseline graft injury in these two groups. Grafts from LD were characterized by activation of transcripts related to anti-ischemic and regenerative processes and fewer pro-inflammatory gene transcripts. This transcriptional events occurring in liver allografts could allow for the prediction of post-transplant function. Pro-inflammatory and ischemic transcriptional changes in the grafts are directly related to donor type and may be useful targets for the development of future therapeutic strategies.
2013-07-01 | GSE23649 | GEO
Project description:The majority of transplanted organs are recovered from deceased donors after brain death (BD). BD has been hypothesized to compromise organ quality in part from the activation of systemic inflammation. The objective of this study was to characterize the immune response induced by BD in a well controlled non-human primate (NHP) model. Assessment of physiologic parameters (blood pressure, heart rate, urinary output, catecholamines, and cerebral angiograms) was used to confirm BD. After 6h of BD, we monitored changes in the peripheral blood by flow cytometry, liver gene expression by microarray and liver protein expression by Western blotting and immunohistochemistry (IHC). BD was indicated by a rapid increase in blood pressure followed by hemodynamic instability, hypotension, diabetes insipidus and the absence of cerebral blood flow and brain stem reflexes. Within the peripheral blood IL-6 levels and neutrophils increased and myeloid dendritic cells decreased in BD NHP when compared to living donor controls. Genes related to innate inflammatory response and apoptosis were significantly upregulated in BD NHP. BD livers showed increased expression of suppressor of cytokine signaling 3 (SOCS3) protein and the danger associated molecular pattern protein S100A9. Increased expression of intracellular cellular adhesion molecule 1 (ICAM-1) and major histocompatibility complex (MHC) II, neutrophil accumulation, and products of oxidative stress (carboxy methyl lysine (CML) and hydroxynonenal (HNE)) were detected by IHC in livers. Conclusion: These data indicate that BD leads to the rapid activation of an inflammatory response within the liver involving components of the innate immune response at the gene and protein levels. The activation of these inflammatory pathways may provide one explanation for the reduced post-transplant function of organs from brain dead donors. Microarray analysis was performed to compare gene expression patterns from livers recovered after 5 hours of brain death (n=5) and from "living donor" non-brain dead controls (n=5).
2012-06-27 | E-GEOD-22624 | biostudies-arrayexpress
Project description:Liver biopsy samples were obtained from 64 infants with biliary atresia at the time of intraoperative cholangiogram. Liver biopsy samples were obtained from 14 age-matched infants with other causes of intrahepatic cholestasis, and from 7 deceased-donor children. GeneChip® Human Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was specifically regulated in the livers from patients with biliary atresia. Gene expression profiling: Liver biopsy samples obtained from infantas with other causes of intrahepatic cholestasis were served as diseased control. Liver tissue obtained from deceased-donor children were served as normal control. A molecular signataure of biliary atresia at the time of diagnosis was identified by comparing hepatic gene expression profile from biliary atresia to those from diseased and normal controls. This dataset is part of the TransQST collection.
2013-06-01 | E-GEOD-46960 | biostudies-arrayexpress