OBJECTIVETo investigate the role of natural killer T cells (NKT) in the pathogenesis and staging of endometriosis (EMT).

METHODSSixty EMT cases of stages I to IV were enrolled as the observation group, and 20 healthy volunteers served as the control group. NKT percentages in the peripheral blood and peritoneal effusions were detected by flow cytometry, and the levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were examined using ELISA.

RESULTSCompared with the control group, EMT group showed significantly lowered NKT percentages and IFN-γ and IL-4 levels in both the peripheral blood and peritoneal effusions (P<0.05). In EMT patients, NKT percentages, IFN-γ and IL-4 levels all increased significantly with the stage of EMT in the order of I>II>III>IV (P<0.05). Spearman correlation analysis showed that NKT, IFN-γ and IL-4 were all inversely correlated with the stage of EMT (r>0.06, P<0.05).

CONCLUSIONAs a protective factor against EMT, NKT, together with its cytokines IFN-γ and IL-4, play an important role in EMT and is closely correlated with EMT staging.

Case-Control Studies ; Endometriosis ; metabolism ; pathology ; Female ; Flow Cytometry ; Humans ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Natural Killer T-Cells ; metabolism

To evaluate the correlation of the serum uric acid and free fatty acid (FFA) levels in Shandong coastal residents. To investigate the correlation between serum uric acid and FFA based on 3860 individuals who have been long staying in Qingdao, Yantai, Weihai, Rizhao with a randomized, stratified cluster sampling method. According to FFA quartile, subjects were divided into four groups: group Q1 of 908, group Q21016, group Q3958, and group Q4978 cases. The prevalence of hyperuricemia and serum uric acid levels increased with the increasing FFA quartile. Compared with Q1, Q2, and Q3 groups, the prevalence of hyperuricemia in Q4 group and the increase of serum uric acid were statistically significant(P<0. 05). And in the group Q4, hyperuricemia prevalence is twice as the group A. According to the serum uric acid level, subjects were divided into the normal uric acid group(n=3331) and the hyperuricemia group ( n = 529). In the hyperuricemia group, their systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, triglycerides, total cholesterol, low density lipoprotein-cholesterol (LDL-C), glucose, uric acid, FFA, body mass index etc. were significantly higher than those of the normal uric acid group (all P<0. 01), while the high density lipoprotein-cholesterol ( HDL-C), cystatin, glomerular filtration rate (eGFR) are significantly lower than those of the normal uric acid group( all P<0. 01). Serum uric acid levels are positively correlated with systolic and diastolic blood pressures, waist and hip circumferences, triglycerides, total cholesterol, LDL-C, FFA, blood glucose, body mass index (all P<0. 01); and negatively correlated with eGFR (P<0. 01). Multiple regression analysis showed that systolic blood pressure, FFA, total cholesterol, triglycerides, LDL-C, blood glucose, body mass index, eGFR were factors influencing serum uric acid independently. Multivariate binary logistic regression analysis showed that systolic blood pressure, waist circumference, total cholesterol, blood glucose, and FFA are independent risk factors to predict hyperuricemia onset while eGFR is a protective factor. Serum uric acid level is closely related to the free fatty acid, and FFA seems to be involved in the development and progression of hyperuricemia.

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.