With IL-6R as target, a new compound 2460A was identified from fungus using HTS screening model. The taxonomics of the produced strain was confirmed to be Trichoderma hazianum rifai after sequencing analysis of rDNA-ITS (internal transcribed spacer). Results showed that this compound has a binding activity on IL-6R competed with IL-6, thus it is a new ligand of IL-6R originating from microbe. With MTT assay, the anti-tumor activities of 2460A were demonstrated on CM126 and HT-29 cell lines separately, the IC50 are 2.17 x 10(-5) mol x L(-1) and 1.8 x 10(-5) mol x L(-1) respectively. The compound affected lightly the HT-29 cell cycle at S phase. Studies for the anti-tumor activity of 2460A in vivo are in progress in our lab.

Aim To investigate the hypoglycemic pathway of terpenes from Cornus officinalis(TCF) from three aspects of insulin dependence, α-glucosidase inhibition, insulin sensitizing.Methods Insulin-deficient diabetes mellitus(DM) model was induced by tail vein injection of streptozotocin(STZ) into SD rats at the dose of 50mg·kg-1 body weight.Rats were randomly divided into seven groups: control group(CON), model group(Model), metformin group(Met) 0.1g·kg-1, shenqi jiangtang granules(Shenqi) group 1.0 g·kg-1, three dose groups of TCF: 0.10, 0.05, 0.025 g·kg-1.Body weight and blood glucose were measured every week.After four weeks, glycosylated hemoglobin (HbA1c), glycosylated serum protein (GSP) were determined.Normal ICR mice were divided into seven groups: CON, Model, Met group 0.2g·kg-1, acarbose group(Acar) 0.1 g·kg-1, Shenqi group 1.5g·kg-1, three dose groups of TCF: 0.20g·kg-1;0.10g·kg-1;0.05 g·kg-1.After 10 days of administration, intraperitoneal injections of glucose and gavage starch tolerance tests were employed.Normal SD rats were divided into six groups: CON, rosiglitazone group 0.02 g·kg-1, glipizide group 0.02 g·kg-1, three dose groups of TCF: 0.10, 0.05, 0.025 g·kg-1.After seven days of administration, intraperitoneal glucose tolerance test(IPGTT) was employed and levels of insulin was determined.Results (1)High dose of TCF significantly reduced the level of HbA1c(P<0.05), GSP(P<0.05) on STZ model rats;(2)TCF significantly improved the glucose tolerance and gavage starch tolerance in ICR mice(P<0.05);(3) High dose of TCF significantly reduced the blood glucose and serum insulin level.Conclusions TCF has obvious effects on inhibiting glucose absorb and promoting the use of glucose.It is able to exert hypoglycemic effect through non-insulin dependent pathway, whereas, whether it has the effects of α-glucosidase inhibition and insulin sensitization should be further validated.

To investigate the hypoglycemic effects of terpenes from Fructus Corni(TFC)on type 2 diabetes mellitus, the db/db diabetic mice were intragastrically administered with 25, 50, 100 mg/kg of TFC for 10 weeks. The fasting blood glucose, insulin(Ins), glycosylated serum protein(GSP), total cholesterol(TC)and triglyceride(TG)levels were determined. At weeks 8 and 10, intraperitoneal injections of glucose and gavage starch tolerance tests were performed, respectively. The db/db mice showed obvious obesity. Each dose of TFC could significantly reduce the body weight of db/db mice(P< 0. 05). After 4 weeks of administration, all doses of TFC significantly reduced the fasting blood glucose of db/db mice(P< 0. 05). The serum TC, TG levels were also significantly decreased in the TFC middle- and high-dose groups(P< 0. 05). In addition, middle- and high-dose of TFC could significantly reduce the level of GSP. Middle- and high-dose of TFC also significantly improve the glucose tolerance and gavage starch tolerance in db/db mice(P< 0. 05). These results suggest that TFC could improve diabetes-related symptoms via regulating glucose and lipids metabolism.

[摘 要] 目的：分析甲状旁腺激素样激素（PTHLH）基因与肺鳞状细胞癌（LSCC）患者预后及其与肿瘤微环境（TME）免疫细胞浸润的相关性。方法：通过UALCAN、TIMER、cBioPortal数据库在泛癌水平分析PTHLH在泛癌中的表达情况，运用Kaplan-Meier Plotter数据库分析PTHLH在LSCC中的表达及其与患者的预后关联。选用2017年1月至2020年12月在甘肃省肿瘤医院手术切除的24例LSCC患者的癌及癌旁组织标本，用qPCR和WB法分别检测LSCC组织中PTHLH mRNA和蛋白的表达，用qPCR法检测各种趋化因子和MHC分子的表达水平。采用TIMER数据库联合CIBERSORT反卷积法分析PTHLH基因表达和LSCC的TME中免疫细胞浸润的关系。结果：LSCC组织中PTHLH mRNA和蛋白的表达水平均显著高于癌旁组织（均P<0.05），且PTHLH高表达LSCC患者的OS明显缩短（P<0.01）。PTHLH的表达与LSCC患者TME密切相关（P<0.01）。PTHLH的表达与B细胞、CD8+ T细胞、CD4+ T细胞、中性粒细胞和DC等免疫浸润呈显著负相关（r=-0.142、-0.123、-0.224、-0.166、-0.213，均P<0.01）。PTHLH高表达抑制趋化因子、MHC分子的表达，从而抑制炎症反应、免疫浸润、抗肿瘤免疫反应等。PTHLH的表达与免疫检查点分子CTLA-4、PDCD1、TIGIT呈负相关（r=-0.340、-0.441、-0.38，均P<0.01）。结论：PTHLH与肿瘤免疫抑制相关，有望成为预测LSCC患者预后和免疫治疗效果的潜在生物标志物。