Purpose The glucosamine and chondroitin compound tablets were prepared. The anti-inflammatory and analgesic effects of glucosamine and chondrotin compound tablets were investigated. Methods The proportion of glucosamine and chondroitin was 5:4 to prepare compound tablets. The anti-inflammatory effect was investigated with carrageen-induced rats paw edema and cotton granuloma in rats. The analgesic effect was investigated using the pain models of mice which were induced by 0.6% acetic acid. Results Compared with control group the degree of paw edema in the low, middle and high dose group was decreased ( P < 0.05). Fourtreatment groups compared with control group respectively at the weight of granuloma were also markedly reduced ( P < 0.05) and the writhing number of mice induced by acetic acid was decreased ( P < 0.05 ) . Conclusion glucosamine and chondroitin compound tablets have anti-inflammatory effect and analgesic effect on models induced by acetic acid.

Objective To investigate the anti-inflammatory and analgesic effects of combined application of glucosamine(GS)and chondroitin sulfate(CS).Methods The acute and chronic anti-inflammatory effects of combined application of GS and CS were observed respectively through carrageen-induced paw edema and cotton-induced inguinal granuloma of rats.The analgesic effect of combined application of GS and CS was investigated by the mouse pain model induced by 0.6% acetic acid Results As compared with the control group,the degree of paw edema and the weight of granuloma in combined application of GS and CS group were significantly reduced(P<0.05 and P<0.01,respectively);and the writhing number of mice decreased significantly(P<0.05).Conclusion Combined application of glucosamine and chondroitin sulfate demonstrates obviously anti-inflammatory and analgesic effects.

PD-1 and CTLA-4 antibodies offer great hope for cancer immunotherapy. However, many patients are incapable of responding to PD-1 and CTLA-4 blockade and show low response rates due to insufficient immune activation. The combination of checkpoint blockers has been proposed to increase the response rates. Besides, antibody drugs have disadvantages such as inclined to cause immune-related adverse events and infiltration problems. In this study, we developed a cyclic peptide C25 by using Ph.D.-C7C phage display technology targeting LAG-3. As a result, C25 showed a relative high affinity with human LAG-3 protein and could effectively interfere the binding between LAG-3 and HLA-DR (MHC-II). Additionally, C25 could significantly stimulate CD8 T cell activation in human PBMCs. The results also demonstrated that C25 could inhibit tumor growth of CT26, B16 and B16-OVA bearing mice, and the infiltration of CD8 T cells was significantly increased while FOXP3 Tregs significantly decreased in the tumor site. Furthermore, the secretion of IFN- by CD8 T cells in spleen, draining lymph nodes and especially in the tumors was promoted. Simultaneously, we exploited T cells depletion models to study the anti-tumor mechanisms for C25 peptide, and the results combined with MTT assay confirmed that C25 exerted anti-tumor effects CD8 T cells but not direct killing. In conclusion, cyclic peptide C25 provides a rationale for targeting the immune checkpoint, by blockade of LAG-3/HLA-DR interaction in order to enhance anti-tumor immunity, and C25 may provide an alternative for cancer immunotherapy besides antibody drugs.

Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.