Tumor-Activated T

Human γδ T cells display the principal characteristics of professional antigen-presenting cells (APCs), in addition to playing a vital role in immunity through cytokine secretion and their cytotoxic activity. However, it is not clear whether γδ T cells perform APC-like functions under pathological conditions. In this study, we showed that, in contrast to peripheral-derived γδ T cells directly isolated from PBMCs of gastric cancer patients, tumor-activated γδ T cells not only killed tumor cells efficiently but also strongly induced primary CD4(+) and CD8(+)   αβ T cells proliferation and differentiation. More importantly, they abrogated the immunosuppression induced by CD4(+)CD25(+) Treg cells and induced the cytotoxic function of CD8(+)   αβ T cells from patients with gastric cancer. In conclusion, tumor-activated γδ T cells can induce adaptive immune responses through their APC-like functions, and these cells may be a potentially useful tool in the development of tumor vaccines and immunotherapy

Gut microbiota mediates positive effects of liraglutide on dyslipidemia in mice fed a high-fat diet

Except for improving glycemic control, liraglutide, one of the glucagon-like peptide-1 receptor agonists, has exerted promising therapeutic effects for dyslipidemia. It has been proved that gut microbiota plays a dramatic role in regulating lipid metabolism. This study aims to explore whether liraglutide could improve dyslipidemia by modulating the gut microbiota in mice fed a high-fat diet (HFD). The C57BL/6 mice were fed a HFD to establish an animal model of dyslipidemia, and then administered with liraglutide or normal saline (NS) for 12 weeks. Indices of glucolipid metabolism were evaluated. Gut microbiota of the mice was analyzed by 16S rRNA gene sequencing. Compared with HFD group, liraglutide significantly alleviated weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels, meanwhile elevating high-density lipoprotein cholesterol (HDL) levels (all p < 0.05). The gut microbiota analysis revealed that liraglutide greatly reduced the relative abundance of Firmicutes and augmented that of Bacteroidetes, with a concomitant drop in the Firmicutes/Bacteroidetes ratio. Meanwhile, liraglutide dramatically changed the overall composition, promoted the growth of beneficial microbes (Akkermansia, Lactobacillus, Parabacteroides, Oscillospira, etc.), and inhibited the growth of harmful microbes (AF12, Shigella, Proteobacteria, Xenorhabdus, etc.). Especially, the relative abundance of Akkermansia increased the most after liraglutide treatment. Correlation analysis suggested that TC and LDL were positively correlated with some harmful bacteria, and negatively associated with beneficial bacteria. This study confirmed that liraglutide had a certain therapeutic effect on dyslipidemia in HFD-fed mice and could regulate the composition of the gut microbiota associated with lipid metabolism, especially Akkermansia. Thus, affecting gut microbiota might be a potential mechanism of liraglutide in attenuating dyslipidemia

Protein Targeting to Glycogen (PTG): A Promising Player in Glucose and Lipid Metabolism

Protein phosphorylation and dephosphorylation are widely considered to be the key regulatory factors of cell function, and are often referred to as “molecular switches” in the regulation of cell metabolic processes. A large number of studies have shown that the phosphorylation/dephosphorylation of related signal molecules plays a key role in the regulation of liver glucose and lipid metabolism. As a new therapeutic strategy for metabolic diseases, the potential of using inhibitor-based therapies to fight diabetes has gained scientific momentum. PTG, a protein phosphatase, also known as glycogen targeting protein, is a member of the protein phosphatase 1 (PP1) family. It can play a role by catalyzing the dephosphorylation of phosphorylated protein molecules, especially regulating many aspects of glucose and lipid metabolism. In this review, we briefly summarize the role of PTG in glucose and lipid metabolism, and update its role in metabolic regulation, with special attention to glucose homeostasis and lipid metabolism

Association between Circulating Ectodysplasin A and Diabetic Kidney Disease

Background. Ectodysplasin A (EDA), a member of the TNF family, plays important roles in ectodermal development, while recent studies expanded its regulatory effects on insulin resistance and lipid metabolism. This study was the first time to investigate the correlation between circulating EDA and albuminuria in patients with T2DM. Methods. A total of 189 T2DM and 59 healthy subjects were enrolled in the study. We analyzed the concentrations of EDA by ELISA. Plasma glucose, insulin, HbA1c, lipids, creatinine, BUN, and UACR were also measured. Insulin resistance and pancreatic cell function were assessed by HOMA. Results. Circulating EDA concentration was significantly increased in T2DM patients and increased with the degree of albuminuria. EDA was positively correlated with age, FIns, HOMA-IR, HOMA-β, Scr, and UACR, and negatively correlated with eGFR. Linear stepwise regression showed that FIns, HOMA-β, and UACR were independent influencing factors of EDA. Logistic regression analysis showed that EDA was independently associated with the occurrence of albuminuria in T2DM. ROC curve showed that EDA had an area under the receiver operating curve of 0.701 [95%CI=0.625−0.777, P<0.001]. Conclusion. EDA is positively correlated with the degree of albuminuria in patients with T2DM and may be involved in the occurrence and progression of diabetic kidney disease (DKD)

Tumor-Activated TCRγδ+ T Cells from Gastric Cancer Patients Induce the Antitumor Immune Response of TCRαβ+ T Cells via Their Antigen-Presenting Cell-Like Effects

Human γδ T cells display the principal characteristics of professional antigen-presenting cells (APCs), in addition to playing a vital role in immunity through cytokine secretion and their cytotoxic activity. However, it is not clear whether γδ T cells perform APC-like functions under pathological conditions. In this study, we showed that, in contrast to peripheral-derived γδ T cells directly isolated from PBMCs of gastric cancer patients, tumor-activated γδ T cells not only killed tumor cells efficiently but also strongly induced primary CD4+ and CD8+  αβ T cells proliferation and differentiation. More importantly, they abrogated the immunosuppression induced by CD4+CD25+ Treg cells and induced the cytotoxic function of CD8+  αβ T cells from patients with gastric cancer. In conclusion, tumor-activated γδ T cells can induce adaptive immune responses through their APC-like functions, and these cells may be a potentially useful tool in the development of tumor vaccines and immunotherapy