avoiding-ischemia-reperfusion-injury-in-liver-transplantation

Avoiding Ischemia Reperfusion Injury in Liver Transplantation

Currently, ex situ machine perfusion is a burgeoning technique that provides a better preservation method for donor organs than conventional static cold ...

Sun Yat-sen University

Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology

Guangdong Provincial International Cooperation Base of Science and Technology

Allograft rejection has been an obstacle for long-term survival of patients for many years. Current strategies for transplant rejection are not as optimal as we expected, especially for long-term treatments. Trichinella spiralis, a nematode parasitized in mammalian muscle and as an invader, maintains harmonious with host in the long term by evading host immune attack. To determine whether T. spiralis infection impacts on allograft rejection, we performed mice cardiac allograft transplantation model by using BALB/c (H-2(b)) mice as donors and C57BL/6 (H-2(b)) mice orally infected with 300 muscle larvae for 28 days as recipients. Graft survival was monitored by daily palpation of the abdomen; histologic change was observed by H&E stain; and CD4(+), CD8(+), CD4(+)IFN-γ(+), and CD4(+)IL-17(+) T cells and regulatory T cells were examined with the use of flow cytometry. Serum cytokine levels were measured by Luminex. Finally, we found that mean survival time of cardiac allografts in T. spiralis group was 23.40 ± 1.99 days, while the vehicle control group was 10.60 ± 0.75 days. Furthermore, we observed alleviated histological changes in the heart allograft, decreased corresponding CD8(+) T cells, suppressed Th1 and Th17 responses, and increased regulatory T cell frequency in a murine cardiac transplantation model at day 7 post-transplantation in experimental group. These data suggest that T. spiralis infection resulted in prolonged allograft survival following murine cardiac transplantation, with suppressed Th1/Th17 responses and augmented regulatory T cells.

Trichinella spiralis infection changes immune response in mice performed abdominal heterotopic cardiac transplantation and prolongs cardiac allograft survival time.

Activation of hepatic stellate cells (HSCs) is an essential event in the initiation and progression of liver fibrosis. HSCs are believed to be the major source of collagen-producing myofibroblasts in fibrotic livers. A key feature in the pathogenesis of liver fibrosis is fibrillar Collagen I (Col 1) deposition. Osteopontin (OPN), an extracellular matrix (ECM) cytokine expressed in HSCs, could drive fibrogenesis by modulating the HSC pro-fibrogenic phenotype and Col 1 expression. Here, we aimed to investigate the molecular mechanism of OPN regulating the activation of HSCs. Our results showed that hepatic expression of OPN was increased in patients with liver fibrosis. In addition, hepatic OPN was positively correlated with Col 1 and α-SMA. Recombinant OPN (rOPN) upregulated Col 1 and α-SMA expression in LX-2 cells. However, OPN knockdown downregulated Col 1 expression. The 3'-UTR of the collagen 1 (Col 1) was identified to bind miR-129-5p. Transfection of miR-129-5p mimic in HSC resulted in a marked reduction of Col 1 expression. Conversely, a decrease in miR-129-5p in HSCs transfected by anti-sense miR-129-5p (AS-miR-129-5p) caused Col 1 upregulation. Furthermore, luciferase reporter assay showed that miR-129-5p directly target the 3'-UTR of Col1α1 mRNA via repressing its post-transcriptional activities. Finally, miR-129-5p level was decreased in fibrotic liver of human, and reduced by rOPN treatment. In contrast, miR-129-5p was induced in HSCs transfected by OPN siRNA. These data suggested that OPN induces Col 1 expression via suppression of miR-129-5p in HSCs.

Osteopontin promotes collagen I synthesis in hepatic stellate cells by miRNA-129-5p inhibition.

Corrigendum to "Osteopontin promotes collagen I synthesis in hepatic stellate cells by miRNA-129-5p inhibition" [Exp. Cell Res. 362(2) (2018) 343-348].

Inflammation, oxidative stress, and dyslipidemia are major factors in the pathogenesis of atherosclerosis. Andrographolide, a bioactive component of Andrographis paniculata, has several biological activities, including anti-inflammatory, antioxidant, and anticancer effects. This study shows that andrographolide downregulates the oxidized low-density lipoprotein (oxLDL)-induced expression of the pro-inflammatory molecules monocyte chemotactic protein (MCP)-1 and interleukin (IL)-6 and blocks the nuclear factor-κB signaling pathway in macrophages. Additionally, andrographolide treatment decreased reactive oxygen species (ROS) generation in oxLDL-induced macrophages, indicating that the compound can decrease oxidative stress. The results also suggest that andrographolide suppresses oxLDL-induced foam cell formation and inhibits oxLDL-induced CD36 expression in vitro. Furthermore, in vivo studies have indicated that andrographolide treatment ameliorates atherosclerosis pathogenesis in apolipoprotein E knockout mice. Therefore, by suppressing inflammation, ROS generation, and foam cell formation, andrographolide may ameliorate the progression of atherosclerosis, suggesting its potential as a therapeutic drug for the prevention and/or treatment of this disease.

Andrographolide Ameliorates Atherosclerosis by Suppressing Pro-Inflammation and ROS Generation-Mediated Foam Cell Formation.

Liver transplantation (LT) is an effective option for hepatocellular carcinoma (HCC) and end-stage liver cirrhosis. However, organ shortage and tumor recurrence are the main obstacles limiting its popularization and application in HCC patients. Testing for circulating tumor cells (CTCs) would be a valuable strategy to predict the recurrence and metastasis of HCC after LT. Various CTCs detection methods have different advantages and disadvantages. This study aims to investigate the predictive value of testing for CTCs based on immunofluorescence in situ hybridization of peripheral blood cells in patients with HCC after LT.

Article	Year
Trichinella spiralis infection changes immune response in mice performed abdominal heterotopic cardiac transplantation and prolongs cardiac allograft survival time. Parasitology research\| PubMed ID: 26481486	2016
Osteopontin promotes collagen I synthesis in hepatic stellate cells by miRNA-129-5p inhibition. Experimental cell research\| PubMed ID: 29196165	2018
Corrigendum to "Osteopontin promotes collagen I synthesis in hepatic stellate cells by miRNA-129-5p inhibition" [Exp. Cell Res. 362(2) (2018) 343-348]. Experimental cell research\| PubMed ID: 29336781	2018
Andrographolide Ameliorates Atherosclerosis by Suppressing Pro-Inflammation and ROS Generation-Mediated Foam Cell Formation. Inflammation\| PubMed ID: 29948505	2018
Analysis of preoperative circulating tumor cells for recurrence in patients with hepatocellular carcinoma after liver transplantation. Annals of translational medicine\| PubMed ID: 33145286	2020

Yinghua Chen

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