Project description:Tumor-infiltrating T lymphocytes (TILS) plays a pivotal role in immunotherapy, but the dynamic relationships of the T cells reacted on the therapy remains elusive. T cell receptor (TCR) repertoire, serving as lineage tags, could track these tumor-infiltrating T lymphocytes. Here, in order to deconvolve TILS heterogeneity after therapy in a comprehensive catalog, we presented single T-cell analysis by RNA-seq and TCR tracking of a 22,590 T cells from colorectal carcinoma under control conditions and during Stellera chamaejasme and anti-PD-1 activation. We reveal a highly complex microenvironment which profoundly molds T lymphocytes, as well as the combinatorial impact of TCR utilization on phenotypic diversity. scRNA-seq identified distinct CD8 T cells subtypes CD8 naïve and CD8 cytoxic cells(CD8 CTL), also, CD4 T cell subpopulations Regulatory T(Tregs) cells and T helper cell 17(Th-17). Stellera chamaejasme activation triggered CTSW, ICOS, etc. in CD8 T cells, whose the dramatic differentiation into from a single time point. At the same time, Stellera chamaejasme plus anti-PD-1 therapy have a strikingly effect on the balance between Tregs and Th-17. Our integrated analyses provide a powerful avenue to disclose the TILS in CRC based on TCR and demonstrate novel functional interactions among TILS subpopulations during Stellera chamaejasme plus anti-PD-1 therapy.
Project description:Bioassay-guided fractionation of a petroleum ether extract of the roots of Stellera chamaejasme led to the isolation of seven new (stelleralides D-J, 1-7) and 12 known (8-19) daphnane diterpenoids. The structures and relative configurations of 1-7 were established on the basis of extensive spectroscopic analysis, including HRESIMS and comprehensive NMR techniques. All isolates were evaluated for anti-HIV activity in MT4 cells. All compounds tested, except 2, showed anti-HIV activity, and, especially, five 1?-alkyldaphnane diterpenoids (3, 4, 5, 10, and 11) exhibited extremely potent anti-HIV activity, with EC50 values of 0.06-1.1 nM and selectivity index values of more than 10,000.
Project description:A new dicoumarinyl ether, 3-hydroxy-6-methoxy-7,7'-dicoumarinyl ether (1), was isolated from the roots of Stellera chamaejasme L, together with the known compound umbelliferone (2). Their structures were determined on the basis of spectroscopic techniques, including IR, NMR, and HR-ESI-MS.
