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1. chinaXiv:201711.02415 [pdf]

Visualization?and?Quantification?of?Browning?Using?a?Ucp1-2A-Luciferase Knock-in Mouse Model

Mao, LF; Nie, BM; Nie, T; Hui, XY; Gao, XF; Lin, XL; Liu, X; Xu, Y; Tang, XF; Yuan, R; Li, K; Li, P; Ding, K; Wang, Y; Xu, AM; Fei, J; Han, WP; Liu, PT; Madsen, L; Kristiansen, K
Subjects: Biology >> Ecology

Both mammals and adult humans possess classic brown adipocytes and beige adipocytes, and the amount and activity?of?these adipocytes are considered key factors in combating obesity and its associated metabolic diseases. Uncoupling protein 1 (Ucp1) is the functional marker?of?both brown and beige adipocytes. To facilitate?a?reliable, easy, and sensitive measurement?of?Ucp1 expression both in vivo and in vitro, we generated?a?Ucp1-2A-luciferase knock-in mouse by deleting the stop codon for the mouse Ucp1 gene and replacing it with?a?2A peptide. This peptide was followed by the luciferase coding sequence to recapitulate the expression?of?the Ucp1 gene at the transcriptional and translational levels. With this mouse, we discovered?a?cold-sensitive brown/beige adipose depot underneath the skin?of?the ears, which we named uBAT. Because?of?the sensitivity and high dynamic range?of?luciferase activity, the Ucp1-2A-luciferase mouse is useful for both in vitro quantitative determination and in vivo?visualization?of?nonshivering thermogenesis. With the use?of?this model, we identified and characterized axitinib, an oral small-molecule tyrosine kinase inhibitor, as an effective?browning?agent.

submitted time 2017-11-17 Hits1048Downloads617 Comment 0

2. chinaXiv:201711.02416 [pdf]

Toll-like?receptor?2?costimulation?potentiates?the?antitumor?efficacy?of?CAR?T?Cells.

Lai, Y; Weng, J; Wei, X; Qin, L; Lai, P; Zhao, R; Jiang, Z; Li, B; Lin, S; Wang, S; Wu, Q; Tang, Z; Liu, P; Pei, D; Yao, Y; Du, X; Li, P
Subjects: Biology >> Ecology

Chimeric antigen receptor (CAR) T-cell immunotherapies have shown unprecedented success in treating leukemia but limited clinical efficacy in solid tumors. Here, we generated 1928zT2 and m28zT2, targeting CD19 and mesothelin, respectively, by introducing the Toll/interleukin-1 receptor domain of Toll-like receptor 2 (TLR2) to 1928z and m28z. T cells expressing 1928zT2 or m28zT2 showed improved expansion, persistency and effector function against CD19+ leukemia or mesothelin+ solid tumors respectively in vitro and in vivo. In a patient with relapsed B-cell acute lymphoblastic leukemia, a single dose of 5 * 104/kg 1928zT2 T cells resulted in robust expansion and leukemia eradication and led to complete remission. Hence, our results demonstrate that TLR2 signaling can contribute to the efficacy of CAR T cells. Further clinical trials are warranted to establish the safety and efficacy of this approach.Leukemia advance online publication, 25 August 2017; doi:10.1038/leu.2017.249.

submitted time 2017-11-17 Hits1156Downloads721 Comment 0

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