1.Research advances of encapsulation and co-delivery modes during islet transplantation
Zuhan CHEN ; Ruiyang MA ; Jingwen WANG ; Huanjing BI ; Xiaoming DING
Chinese Journal of Organ Transplantation 2023;44(8):502-507
This review summarized the latest advances in islet transplantation, islet encapsulation and co-delivery strategies of cell and growth factors.
2.Study of adverse drug events related to tacrolimus in pediatric solid organ transplant recipients based on FAERS database
Boqing DONG ; Jingwen WANG ; Huanjing BI ; Zuhan CHEN ; Cuinan LU ; Wujun XUE ; Yang LI ; Xiaoming DING
Organ Transplantation 2024;15(4):581-590
Objective To investigate the characteristics of adverse drug event (ADE) related to tacrolimus (Tac) in pediatric solid organ transplant recipients. Methods The data were retrieved from the US Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the second quarter of 2023. The ADE data of pediatric organ transplant recipients with Tac as the primary suspected drug were extracted. The relationship between Tac and ADE was quantitatively analyzed by proportional imbalance method. Basic characteristics and signal strength of ADE related to Tac were analyzed. ADE related to Tac in children of different ages and different types of organ transplantation were analyzed. Results A total of 1 443 children's ADE reports involving Tac were screened, including 188 cases (13.0%) of heart transplantation, 668 cases (46.3%) of liver transplantation, 531 cases (36.8%) of kidney transplantation and 56 cases (3.9%) of lung transplantation. The median age of children was 10 years old. The top three countries with ADE reporting were the United States, France and the United Kingdom. China reported 26 cases, accounting for 1.8%. Infection and infectious diseases accounted for the highest proportion (20.96%) in ADE related to Tac, including EB virus and cytomegalovirus infection, etc. Infection and infectious diseases occupied the largest proportion of ADE related to Tac in children of different ages, whereas the pathogen types were different. Rejection, unstable immunosuppression level and renal function damage were also common ADE related to Tac in children of all ages. Nervous system disease was the main ADE in heart transplant recipients, while infection and infectious diseases were more common in liver and kidney transplant recipients. Rejection was the most common ADE in lung transplant recipients. Conclusions ADE related to Tac possess different distribution characteristics in different types of organ transplantation. Extensive attention should be paid to individualized drug monitoring and risk assessment in pediatric organ transplant recipients, thereby optimizing Tac treatment and reducing the risk of ADE.
3.Analysis of the molecular mechanism of pancreatic islet ischemic injury and identification of core transcription factors based on single-cell transcriptomics
Boqing DONG ; Ying WANG ; Chenge WANG ; Huanjing BI ; Jingwen WANG ; Ruiyang MA ; Jin ZHENG ; Wujun XUE ; Xiaoming DING ; Yang LI
Organ Transplantation 2024;15(6):920-927
Objective To explore the molecular mechanisms and cell-cell interactions in the injury process of pancreatic islet transplantation. Methods Single-cell transcriptome data from mouse islets treated with inflammatory factors were used, and data processing was performed using the Seurat package, with integrated data to remove batch effects. Cell subpopulations were annotated based on known markers. Cell-cell interactions in the inflammatory factor-treated group were analyzed using the CellChat package, and inferred based on the expression of cell surface receptors and ligands. Gene set enrichment analysis was used to clarify the biological processes enriched in β-cells after treatment with inflammatory factors. Finally, differentially expressed transcription factors were identified and verified using microarray datasets of donor islet ischemic injury and Western blotting. Results A total of 7 different cell subpopulations were found in mouse islets, with β-cells being the most abundant. Cell-cell interaction network analysis showed that the number and strength of interactions between ductal cells and other cells were the highest. Gene set enrichment analysis showed that after treatment with inflammatory factors, the immune response was positively enriched in β-cells, while peptide hormone metabolism, bile acid metabolism, and ion homeostasis were downregulated. The common differential transcription factors identified in the mouse single-cell transcriptome and the microarray dataset of donor islet ischemic injury were early growth response 1 (EGR1), nuclear factor-κB inhibitor α (NFKBIA), and activating transcription factor 3 (ATF3). Among them, NFKBIA and ATF3 were upregulated, while EGR1 was downregulated. The expression of EGR1 protein was downregulated after 24 h, 48 h, and 72 h of cold ischemia. Conclusions EGR1 is a transcription factor closely related to islet cold ischemia, and future research should focus on the specific mechanisms of EGR1 and its downstream target genes, in order to provide more effective strategies for clinical treatment of islet transplantation.