Browsing by Author "Liu, Xinyao"

Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    Dose-related immunomodulatory effects of recombinant TRAIL in the tumor immune microenvironment
    (2023-08-22) Wang, Xupu; Wang, Lizheng; Liu, Wenmo; Liu, Xinyao; Jia, Xinyuan; Feng, Xinyao; Li, Fangshen; Zhu, Rui; Yu, Jiahao; Zhang, Haihong; Wu, Hui; Wu, Jiaxin; Wang, Chu; Yu, Bin; Yu, Xianghui
    Abstract Background In addition to specifically inducing tumor cell apoptosis, recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has also been reported to influence the cancer immune microenvironment; however, its underlying effects and mechanisms remain unclear. Investigating the immunomodulatory effects and mechanisms of recombinant TRAIL in the tumor microenvironment (TME) may provide an important perspective and facilitate the exploration of novel TRAIL strategies for tumor therapy. Methods Immunocompetent mice with different tumors were treated with three doses of recombinant TRAIL, and then the tumors were collected for immunological detection and mechanistic investigation. Methodological approaches include flow cytometry analysis and single-cell sequencing. Results In an immunocompetent mouse model, recombinant soluble mouse TRAIL (smTRAIL) had dose-related immunomodulatory effects. The optimal dose of smTRAIL (2 mg/kg) activated innate immune cells and CD8+ T cells, whereas higher doses of smTRAIL (8 mg/kg) promoted the formation of a tumor-promoting immune microenvironment to counteract the apoptotic effects on tumor cells. The higher doses of smTRAIL treatment promoted M2-like macrophage recruitment and polarization and increased the production of protumor inflammatory cytokines, such as IL-10, which deepened the suppression of natural killer (NK) cells and CD8+ T cells in the tumor microenvironment. By constructing an HU-HSC-NPG.GM3 humanized immune system mouse model, we further verified the immunomodulatory effects induced by recombinant soluble human TRAIL (shTRAIL) and found that combinational administration of shTRAIL and trabectedin, a macrophage-targeting drug, could remodel the tumor immune microenvironment, further enhance antitumor immunity, and strikingly improve antitumor effects. Conclusion Our results highlight the immunomodulatory role of recombinant TRAIL and suggest promising therapeutic strategies for clinical application. Graphical Abstract
  • Thumbnail Image
    ItemOpen Access
    Self-Recoverable Dual Physically Cross-Linked Hydrogels Incorporating Hydrophobic Interactions
    (2020-09-23) Liu, Xinyao; Lu, Qingye; Hu, Jinguang; Hua Song, Ke Du
    Over the past few years, self-recoverable hydrogels with desirable mechanical properties have attracted a lot of interests. However, the incorporating of hydrophobic force in hydrogel was not well studied to improve the mechanical properties of self-healing materials compared to electrostatic interactions and hydrogen bonding. In this study, a novel dual physically cross-linked (DPC) hydrogel with self-recoverability was mainly cross-linked and strengthened by hydrophobic interactions between the hydrocarbon chains C8 and C18, in addition to electrostatic and hydrogen bonding between N,N-dimethylacrylamide (DMAc) and cellulose nanocrystal (CNC). C18 alkyl chain was grafted to N-[3-(Dimethylamino)propyl] methacrylamide (DMAPMA) to obtain hydrophobic monomer DMAPMA-C18. Hydrophobic CNC-C8was obtained by grafting C8 to the surface using silane chemistry. Then the DPCCNC-g-DMAc-DMAPMA-C18 (CNC DPC) hydrogels and CNC-C8-g-DMAc-DMAPMA-C18 (CNC-C8 DPC) hydrogels were prepared. The optimum CNC-C8 DPC hydrogel with 0.0675 w/v % DMAPMA-C18 and 0.4 w/v % CNC-C8 possessed excellent elongation of 4267.85%?1445.58%, nominal stress of 331.05?32.06 kPa, true stress of 14463.99?2939.98 kPa, compressive tress of 2822.77 kPa at the strain of 90%, facile self-recovery with tetrahydrofuran on the cut surfaces, as well as high water absorption ability of 19.87?0.64 g/g with well-retained shape.