Polysaccharide of Atractylodis Macrocephalae Rhizoma inhibits expression of immune checkpoint PD-L1 by targeting miR-34a in esophageal carcinoma cells / 中国中药杂志

The immune checkpoint programmed cell death-ligand 1(PD-L1)-mediated immunosuppression is among the important features of tumor. PD-L1, an immunosuppressant, can induce T cell failure by binding to programmed cell death-1(PD-1). Thus, the key to restoring the function of T cells is inhibiting the expression of PD-L1. The Chinese medicinal Atractylodis Macrocephalae Rhizoma(AMR) has the anti-tumor, anti-inflammatory, antioxidant, and hypoglycemic activities, and the polysaccharide in AMR(PAMR) plays a crucial role in immunoregulation, but the influence on the immune checkpoints which are closely related to immunosuppression has not been reported. MicroRNA-34 a(miR-34 a) expression in esophageal carcinoma tissue is significantly lower than that in normal tissue. This study aims to investigate the inhibitory effect of PAMR on esophageal carcinoma cells, and the relationship between its inhibitory effect on PD-L1 expression and miR-34 a, which is expected to clarify the anti-tumor mechanism of PAMR. Firstly, different human esophageal carcinoma cell lines(EC9706, EC-1, TE-1, EC109 cells) were screend out, and expression of PD-L1 was determined. Then, EC109 cells, with high expression of PD-L1, were selected for further experiment. The result showed that PAMR suppressed EC109 cell growth. According to the real-time quantitative PCR(qPCR) and Western blot, it significantly suppressed the mRNA and protein expression of PD-L1, while promoting the expression of tumor suppressor miR-34 a. The confocal microscopy and luci-ferase assay proved that PAMR alleviated the inhibitory effect of PD-L1 while blocked miR-34 a. Additionally, the expression of PD-L1 was controlled by miR-34 a, and the combination of miR-34 a inhibitor with high-dose PAMR reversed the inhibitory effect of PAMR on PD-L1 protein expression. Thus, the PAMR may inhibit PD-L1 by increasing the expression of miR-34 a and regulating its downstream target genes. In conclusion, PAMR inhibits the expression of PD-L1 mainly by inducing miR-34 a.

Neuronal Autophagy in Depression and Regulatory Effect of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Depression is a mental illness characterized by persistent negative feelings， which has seriously threatened people's health. In recent years， neuronal autophagy， an important stress response， has also been regarded as a hypothesis for the pathogenesis of depression. Relevant studies have shown that either insufficient or excessive autophagy triggers neuronal damage， and activated or inhibited neuronal autophagy can be observed in animal models of depression. Therefore， neuronal autophagy may be a double-edged sword involved in the pathogenesis of depression. It is believed in traditional Chinese medicine （TCM） that the occurrence of this disease is closely related to liver depression and spleen deficiency. Chinese medicine regulates the neuronal autophagy via multiple ways. The TCM monomers that regulate neuron autophagy are capable of protecting nerves or penetrating the blood-brain barrier. TCM compounds designed for soothing liver or invigorating spleen have been proved effective against this disease， demonstrating that the core pathogenesis of depression lies in liver depression and spleen deficiency. The regulatory effects of TCM on neuronal autophagy in depression models might result from its action on multiple targets， multiple pathways， and multiple systems. This paper discussed the limitations in current research based on the involvement of neuronal autophagy in depression and its treatments， in order to provide ideas for later similar research and that concerning TCM treatment of depression.