| 3 | The optimization of ultrasonic-microwave assisted synergistic extraction of Lotus plumule extract rich in flavonoids and its hypoglycemic activity显示文摘Lotus(Nelumbo nucifera Gaertn),a kind of perennial aquatic plant,is widely cultivated and consumed by people in Asian countries.Lotus plumule flavonoids(LPF)have been recognized as a hypoglycemic agent.LPF was optimally obtained using novel ultrasonic-microwave assisted synergistic extraction(UMSE)method by response surface methodology(RSM)on the basis of the results of single-factor experiments.Furthermore,the hypoglycemic activity of LPF was investigated by measuring the body weight,fasting blood glucose(FBG)level,and oral glucose tolerance test(OGTT)and analyzing the physiological indexes in streptozotocin-diabetic mice model.The optimum extraction conditions consisted of microwave power 355 W,ultrasonic power 423 W,extraction time 15 min,solid-liquid ratio 1:40,ultrasound/interval time 1/0,and ethanol concentration 70%with the maximum LPF yield of 2.62%.LPF supplementation significantly decreased the body weight,FBG,OGTT,serum total cholesterol(TC),serum total triglycerides(TG),and insulin levels,indicating the antidiabetic activity of LPF.This research verified that the UMSE technique was highly efficient to extract LPF to the maximum extent and the flavonoids from L.plumule exhibited hypoglycemic activity,which showed broad development and application prospects. | Qiuzhe Li Xiaoqing Li Baodong Zheng Chao Zhao | 2021 | Food Production, Processing and Nutrition2021，3，1： | 0 |
| 4 | Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies显示文摘Background:Chimeric antigen receptor T(CAR-T)therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignan-cies,but the cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet to be fully understood.This study aims to explore the molecular deter-minants of cancer cell sensitivity to CAR-T cell-mediated killing and to provide a better understanding of the underlying mechanisms and potential modulation to improve clinical efficacy.Methods:The human whole-genome CRISPR/Cas9-based knockout screening was conducted to identify key genes that enable cancer cells to evade CD19 CAR-T-cell-mediated killing.The in vitro cytotoxicity assays and evaluation of tumor tissue and bone marrow specimens were further conducted to confirm the role of the key genes in cancer cell susceptibility to CAR-T cells.In addition,the specific mechanisms influencing CAR-T cell-mediated cancer clearance were elucidated in mouse and cellular models.Results:The CRISPR/Cas9-based knockout screening showed that the enrich-ment of autophagy-related genes(ATG3,BECN1,and RB1CC1)provided protec-tion of cancer cells from CD19 CAR-T cell-mediated cytotoxicity.These findings were further validated by in vitro cytotoxicity assays in cells with genetic and pharmacological inhibition of autophagy.Notably,higher expression of the three autophagy-related proteins in tumor samples was correlated with poorer respon-siveness and worse survival in patients with relapsed/refractory B-cell lymphoma after CD19 CAR-T therapy.Bulk RNA sequencing analysis of bone marrow samples from B-cell leukemia patients also suggested the clinical relevance of autophagy to the therapeutic response and relapse after CD19 CAR-T cell ther-apy.Pharmacological inhibition of autophagy and knockout of RB1CC1 could dramatically sensitize tumor cells to CD19 CAR-T cell-mediated killing in mouse models of both B-cell leukemia and lymphoma.Moreover,our study revealed that cancer-intrinsic autophagy mediates evasion of CAR-T cells via the TNF-α-TNFR1 axis-mediated apoptosis and STAT1/IRF1-induced chemokine signaling activation.Conclusions:These findings confirm that autophagy signaling in B-cell malig-nancies is essential for the effective cytotoxic function of CAR-T cells and thereby pave the way for the development of autophagy-targeting strategies to improve the clinical efficacy of CAR-T cell immunotherapy. | Lu Tang Huan Zhang Fen Zhou Qiuzhe Wei Mengyi Du Jianghua Wu Chenggong Li Wenjing Luo Jie Zhou Xindi Wang Zhaozhao Chen Yinqiang Zhang Zhongpei Huang Zhuolin Wu Yuxi Wen Huiwen Jiang Danying Liao Haiming Kou Wei Xiong Heng Mei Yu Hu | 2024 | Cancer Communications2024，44，3： | 0 |
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