1.A breakthrough in antibody-drug conjugates in anti-immune rejection
Cailong GUO ; Yuanyi MANG ; Lei ZHANG
Chinese Journal of Tissue Engineering Research 2014;(5):773-778
BACKGROUND:The immunological rejection between host and graft is the leading cause of organ
transplantation failure. The traditional immunosuppressive agents have been unable to meet the needs of clinical treatment. Antibody-drug conjugate, as a type of new drugs, may be hope for the treatment of immune rejection. OBJECTIVE:To comprehensively analyze the composition of antibody-drug conjugates, mechanism of action, clinical research progress as wel as the development trend.
METHODS:A computer-based online retrieval was performed to search papers in CNKI and PubMed database using the key words of ADCs, immunosuppressive agents, immunotoxins, organ transplantation, graft rejection in Chinese and English. Recently published or published in the prestigious journals were selected in the same field. After excluding objective-independent papers and repeated studies, 42 papers were included for further analysis. RESULTS AND CONCLUSION:Antibody-drug conjugates, as highly effective and lowly toxic immunosuppressant, have achieved a breakthrough in treatment of targeting tumor, while the role of it in anti-immune rejection is stil at the exploratory stage. For islet transplantation, novel antibody-drug conjugates are required to block CD8+T effector by CD103/E-Cadherin pathway, and wil probably serve as a potential drug intervention for al ograft rejection.
2.Risk factors of biliary anastomotic stenosis after liver transplantation from donation after cardiac death and therapeutic strategies
Yang GAO ; Xiaoshan LI ; Shengning ZHANG ; Yuanyi MANG ; Gang REN ; Jing LIU ; Laibang LI ; Jianghua RAN ; Li LI
Chinese Journal of Hepatobiliary Surgery 2020;26(9):678-682
Objective:To investigate the related risk factors for biliary anastomotic stenosis after liver transplantation (LT) from donation after cardiac death(DCD) and therapeutic strategies.Methods:The data of 192 patients who received LT from DCD in First Hospital of Kunming from Jan 2010 to Jun 2018 were retrospectively analyzed. A total of 145 patients were enrolled, 85 males and 60 females, with average age 45 years. There was a biliary anastomotic stenosis in 8 cases and no stenosis in 137 cases. Their Chinese criterion for biliary anatomic stenosis, age, body mass index, liver fat, cold/warm ischemia time, unschedule cardiac arrest time, usage of vasopressors, high sodium in the donor were compared, and stenosis related factors were analysed by Spearman correlation analysis.Results:The stenosis was positively correlated with age ( r=0.229), body mass index ( r=0.204), lipoidosis ( r=0.239), duration of hot ischemia ( r=0.214), total duration of unplanned cardiac arrest ( r=0.401), use of booster drugs ( r=0.237), and preoperative donor hypernatremia ( r=0.557) (all P<0.05). Endoscopic biliary stent implantation is effective in the treatment of biliary anastomotic stenosis and has a high success rate. Conclusions:There are many factors related to biliary anastomotic stenosis after DCD liver transplantation, but the better donor maintenance, shorten cold/ warm ischemia time, improved anastomosis will be helpful to reduce biliary complications.As the same time, endoscopic biliary stent placement is the preferred way to treat biliary anastomotic stenosis.
3.LncRNA MALAT1 promotes hepatocellular carcinoma proliferation and invasion by regulating NEAT1 related exosomes secretion
Yuanyi MANG ; Li LI ; Jianghua RAN ; Shengning ZHANG ; Laibang LI ; Yingpeng ZHAO ; Yang GAO ; Jiaojiao ZHAO ; Xiangle HE
Chinese Journal of Hepatobiliary Surgery 2022;28(4):289-294
Objective:To investigate the correlations between expression of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1) and their functions on exosome secretion, proliferation and invasion in hepatocellular carcinoma (HCC).Methods:We used small interfering RNA of MALAT1 (si-MALAT1) to knockdown MALAT1 in HuH-7. At the meanwhile, cells which were transfected with si-NC were used as the negative control group. Expression of NEAT1, cell proliferation and invasion function were detected these two groups. HuH-7 cells were transfected with lentivirus NEAT1 over expressing vector (lv-NEAT1) or negative control (lv-control). Expression of exosomes secretion related genes were analyzed between lv-NEAT1 and lv-control groups. Cells of lv-NEAT1 were knockdown MALAT1 expression using si-MALAT1, which could be si-MALAT1+ lv-NEAT1 group. exosomes secretion was detected in si-NC, si-MALAT1 and si-MALAT1+ lv-NEAT1 group. We treated cells (si-MALAT1 group) with exosomes from cells with lv-NEAT1 or lv-control to divide cells as si-MALAT1+ exosomes of lv-NEAT1 cells and si-MALAT1+ exosomes of lv-control groups. Cell proliferation and invasion of cells were detected in two groups.Results:Low expression of NEAT1 were found in MALAT1 knockdown cells compared with si-NC group [(0.72±0.02) vs. (0.98±0.01), P<0.05]. Cells with MALAT1 knockdown shown diminished proliferation [(0.66±0.03) vs. (0.98±0.04), P<0.05)] and invasion [(88.33±7.26) vs. (147.70±13.62), P<0.05)]. Compared with si-NC group, CD9 and CD63 expression were decreased in exosomes of si-MALAT1 group. Compared with si-MALAT1 group, CD9 and CD63 expression was increased in exosomes of si-MALAT1+ lv-NEAT1 group. Compared with si-MALAT1+ exosomes of lv-control group, proliferation [(0.97±0.03) vs. (0.74±0.05), P<0.05)] and invasion [ (132.70±7.36) vs. (98.33±6.01), P<0.05) ] were increased in si-MALAT1+ exosomes of lv-NEAT1 group. Exosomes related genes expression including HSPA8 (5.53±0.31), SLC3A2 (0.32±0.07) and SLC7A5 (0.77±0.45) were changed in lv-NEAT1 group compared with lv-control group [(0.98±0.15), P<0.05]. Conclusion:MALAT1 induced exosomes secretion by NEAT1 and exosomes related genes regulation. This regulation might be related with increased proliferation and invasion function in HCC cells with MALAT1 and NEAT1 abnormal expression.