1.Effect of adoptive reinfusion of Treg on immune rejection of islet allografts in mice
Junhui LI ; Yuanyu ZHAO ; Meng GUO ; Junsong JI ; Hang YUAN ; Hui WANG ; Qi LU ; Zhiren FU ; Guoshan DING ; Hao YIN
Organ Transplantation 2019;10(6):690-
Objective To investigate the effects of adoptive reinfusion of regulatory T cell (Treg) on the recovery of islet function and graft survival time after islet allograft transplantation. Methods The diabetic model was established using C57BL/6 mice as recipients, and Balb/c mice were chosen as donors for islet allografts transplantation beneath the renal capsule. The recipient mice were divided into 3 groups and 3 mice in each group according to different processing Methods: Treg experiment group (Treg group, 1×106 Treg cells were injected via tail vein at 1 d before operation), positive control group [sirolimus (SRL) group, SRL at a dose of 300 μg/(kg·d) was intragastrically given every day from 1 d before operation] and blank control group (control group, an equivalent volume of normal saline was intragastrically given every day from 1 d before operation). Enzyme-linked immune absorbent assay (ELISA) was used to detect the changes of blood glucose and C-peptide in mice within 14 days after transplantation.
2.Inhibition of islet allograft rejection by Qa-1/PD-L1 artificial liposome
Meng GUO ; Yuanyu ZHAO ; Hao YIN ; Jiayong DONG ; Junsong JI ; Qi LU ; Hang YUAN ; Fei TENG ; Wenyuan GUO ; Guoshan DING
Chinese Journal of Organ Transplantation 2019;40(2):72-77
Objective To explore the effects of Qa-1 and PD-L1 loaded artificial liposomal treatment in allograft rejection and its outcomes .Methods The extracellular domains of Qa-1 and PD-L1 were loaded on liposome surface by streptavidin-biotin system . Mixed lymphocyte reaction (MLR) was performed for measuring Qa-1/PD-L1 liposome biological function .Then liposome was co-transplanted with allo-islets via portal vein .The levels of blood glucose and C-peptide were detected daily after transplantation .Also hepatic lymphocytes after transplantation were isolated for determining the proportion of activated cells and signaling pathway changes .Results Artificial liposome could be easily loaded with biotinylated peptide and its diameter was between 50 to 500 nm . Qa-1/PD-L1 liposome could significantly suppress lymphocyte proliferation , activation and secretion of IFN-γ in MLR by an activation of SHP1/2 and an inhibition of Syk pathway .Qa-1/ PD-L1 liposomes could suppress the activation of hepatic lymphocytes in vivo by activating SHP1/2 ,protecting islet allografts and maintaining a normal level of blood glucose in recipients .Conclusions Qa-1/PD-L1 loaded liposome can effectively suppress allograft rejection and improve the outcomes of islet transplantation .
3.Research progress in risk factors of post-transplantation diabetes mellitus
Junfeng DONG ; Qiang XUE ; Fei TENG ; Yuanyu ZHAO ; Hao YIN
Organ Transplantation 2024;15(1):145-150
Solid organ transplantation has significantly prolonged the survival of patients with end-stage diseases. However, long-term use of immunosuppressants will increase the risk of post-transplantation diabetes mellitus (PTDM) in the recipients, thereby elevating the risk of infection, cardiovascular disease and death. In recent years, with persistent improvement of diagnostic criteria of PTDM, clinicians have deepened the understanding of this disease. Compared with type 2 diabetes mellitus, PTDM significantly differs in pathophysiological characteristics and clinical progression. Hence, different treatment strategies should be adopted. Early identification of risk factors of organ transplant recipients, early diagnosis and intervention are of significance for improving the quality of life of recipients, prolonging the survival of grafts and reducing the fatality of recipients. Therefore, the diagnosis, incidence and risk factors of PTDM were reviewed in this article, aiming to provide reference for clinicians to deliver prompt diagnosis and intervention for PTDM.
4.Research advances in total pancreatectomy with autologous islet cell transplantation
Jingjing LI ; Yuanyu ZHAO ; Hong FU ; Fei TENG ; Jiaxi MAO ; Wenyuan GUO
Journal of Clinical Hepatology 2023;39(10):2506-2512
Since the 1970s, patients with chronic pancreatitis (CP) have benefited from total pancreatectomy with autologous islet cell transplantation (TPAIT). With the continuous development of surgical techniques and perioperative management over the past few decades, there have been improvements in islet cell function, insulin independence rate, and the survival rate of patients. This article summarizes the preoperative indications for TPAIT, the development of surgical operations, postoperative management and monitoring, and prognosis, so as to help clinicians learn more about TPAIT.
5.Analysis of urine Alzheimer-associated neuronal thread protein level and related factors of middle-aged and elderly people in Mianyang
Yurong ZHANG ; Kun FANG ; Renfei ZHANG ; Fang WANG ; Yang LIU ; Ping YANG ; Yan WU ; Lei LI ; Yuanyu ZHAO ; Zhilong CAI ; Jia YANG ; Dan YUAN
Sichuan Mental Health 2023;36(1):53-58
ObjectiveTo investigate the Alzheimer-associated neurofilament protein (AD7c-NTP) in urine of middle-aged and elderly people and its correlation between common metabolites. MethodsA total of 1 150 middle-aged and elderly people who did their physical exmanination in the health examination center of the Sichuan Science City Hospital and the Third Hopital of Mianyang were recruited from March 2017 to March 2020. The level of urine AD7c-NTP were measured by enzyme-linked immunosorbent assay (ELISA), and common metabolites in blood were measured by biochemical analyzer. Based on urine AD7c-NTP level ≤1.5 ng/mL, the objects was divided into normal group (n=956) and elevated group (n=194). Thier demographic data and blood biochemical indicators were collected. ResultsThe urine AD7c-NTP level in middle-aged and elderly people was 0.60(0.30~1.20) ng/mL. The urine AD7c-NTP level was higher in women than that in men [1.04(0.40~1.30) ng/mL vs. 0.84(0.30~1.00) ng/mL, Z=4.202, P˂0.01]. And the urine AD7c-NTP level was lower in the normal group than that in the elevated group [0.50(0.30~0.90) ng/mL vs. 2.10(1.70~2.10) ng/mL, Z=22.035, P˂0.01]. The results of the univariate comparison showed that, the differences between the two groups in age (Z=6.545), fasting glucose (Z=3.506), blood uric acid (Z=2.574), urea nitrogen (Z=2.891), creatinine (Z=2.243), total bilirubin (Z=3.936), glutathione (Z=0.969), total cholesterol (t=3.956) and low density lipoprotein (Z=-5.678) were were statistically significant (P˂0.05 or 0.01). Spearman correlation analysis showed that, the urine AD7c-NTP level was positively correlated with age and the levels of urea nitrogen, glucose, total cholesterol and low density lipoprotein (r=0.177, 0.178, 0.171, 0.109, 0.149, P˂0.01), and negatively correlated with the level of total bilirubin (r=-0.172, P˂0.01). Conclusionthe urine AD7c-NTP level in middle-aged and elderly females was signifitcantly higher than in middle-aged and elderly males.The urine AD7c-NTP level of middle-aged and elderly people was positively correlated with age, urea nitrogen, glucose, total cholesterol and low density lipoprotein, and negatively correlated with total bilirubin.
6.Opportunities and challenges of marginal donor liver
Xinyi LU ; Fei TENG ; Hong FU ; Yuanyu ZHAO ; Liye ZHU ; Jiayong DONG ; Jiaxi MAO ; Wenyuan GUO
Organ Transplantation 2024;15(3):463-468
With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease.
7.I-Evans blue: evaluation of necrosis targeting property and preliminary assessment of the mechanism in animal models.
Qiaomei JIN ; Xin SHAN ; Qi LUO ; Dongjian ZHANG ; Yuanyu ZHAO ; Nan YAO ; Fei PENG ; Dejian HUANG ; Zhiqi YIN ; Wei LIU ; Jian ZHANG
Acta Pharmaceutica Sinica B 2018;8(3):390-400
Necrosis is a form of cell death, which is related to various serious diseases such as cardiovascular disease, cancer, and neurodegeneration. Necrosis-avid agents (NAAs) selectively accumulated in the necrotic tissues can be used for imaging and/or therapy of related diseases. The aim of this study was to preliminarily investigate necrosis avidity of I-evans blue (I-EB) and its mechanism. The biodistribution of I-EB at 24 h after intravenous administration showed that the radioactivity ratio of necrotic to viable tissue was 3.41 in the liver and 11.82 in the muscle as determined by counting in model rats. Autoradiography and histological staining displayed preferential uptake of I-EB in necrotic tissues. nuclear extracts from necrotic cells exhibited 82.3% of the uptake in nuclei at 15 min, as well as 79.2% of the uptake at 2 h after I-EB incubation. The DNA binding study demonstrated that evans blue (EB) has strong binding affinity with calf-thymus DNA (CT-DNA) (=5.08×10 L/(mol/L)). Furthermore, the accumulation of I-EB in necrotic muscle was efficiently blocked by an excess amount of unlabeled EB. In conclusion, I-EB can not only detect necrosis by binding the DNA released from necrotic cells, but also image necrotic tissues generated from the disease clinically.
8.Gli1 promotes epithelial-mesenchymal transition and metastasis of non-small cell lung carcinoma by regulating snail transcriptional activity and stability.
Xueping LEI ; Zhan LI ; Yihang ZHONG ; Songpei LI ; Jiacong CHEN ; Yuanyu KE ; Sha LV ; Lijuan HUANG ; Qianrong PAN ; Lixin ZHAO ; Xiangyu YANG ; Zisheng CHEN ; Qiudi DENG ; Xiyong YU
Acta Pharmaceutica Sinica B 2022;12(10):3877-3890
Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.