1.Effect of up-regulation of miR-132 on expressions of angiopoietin-1/endothelium-specific tyrosine kinase receptor 2 in focal cerebral ischemia reperfusion injury of rats
Peng CHEN ; Chuanlei CHEN ; Aiwu HOU ; Qian GAO ; Shijuan ZHANG ; Xibo SUN ; Bingxuan LI ; Jianyi NIU
Chinese Journal of Neuromedicine 2017;16(8):772-776
Objective To investigate the effect of up-regulation of miR-132 on expressions of angiopoietin-1 (Ang-1)/endothelium-specific tyrosine kinase receptor 2 (Tie2) in focal cerebral ischemia reperfusion injury of rats.Methods Forty adult healthy SD rats were randomly divided into sham-operated group,cerebral ischemia group,miR-132 mimic group and negative control group (n=10).The models of middle cerebral artery occlusion in the later three groups were established by using modified Longa suture method.Rats in the miR-132 mimic group and negative control group were injected miR-132 mimic 15 μg and negative control 15 μg via paracele.Rats in each group were sacrificed 24 h after ischemia,and the brain tissues were collected;the total infarct volumes were calculated by TTC staining.The mRNA expressions ofmiR-132,Ang-1 and Tie2 in ischemic cerebral cortex tissues were detected by real-time fluorescence quantitative PCR.The protein expressions of Ang-1,Tie2,CD31 and vessel endothelial growth factor (VEGF) in ischemic cerebral cortex tissues were detected by Western blotting.Results The total infarct volume in the miR-132 mimic group was (27.92±3.05) mm3,which was significantly smaller than that in the cerebral ischemia group and negative control group ([51.34±2.86] mm3 and [50.46±2.57] mm3,P<0.05).The relative mRNA expression levels of miR-132,A ng-1,Tie2,and the protein expression levels of Ang-1,Tie2,CD31,VEGF in the ischemic cerebral cortex tissues of the miR-132 mimic group were significantly higher than those in the negative control group,cerebral ischemia group and sham-operated group (P<0.05);and those in the negative control group and cerebral ischemia group were significantly higher than those in the sham-operated group (P<0.05).Conclusion Up-regulation ofmiR-132 expression could improve the ischemic states of ischemic stroke in rats,which might be related to Ang-1/Tie2 increased expressions to promote angiogenesis in ischemic brain tissues.
2. Curative effect of fuzheng xiaoliu granules in the treatment of primary liver cancer and analysis of serum metabolomics
Dandan SHI ; Yiyao SUN ; Xiaoqi CHEN ; Fangming YANG ; Chuanlei ZHANG ; Xinting WANG ; Changwei YUAN ; Xinju CHEN
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(11):1247-1262
AIM: To observe the clinical efficacy of Fuzheng Xiaoliu Granules in the treatment of stage II primary liver cancer and to explore its mechanism of action from the perspective of metabolomics. METHODS: Sixty patients with stage II primary liver cancer who achieved complete remission (CR) after comprehensive interventional therapy were randomly divided into treatment group and placebo group, with 30 patients in each group. They were treated for one year and observed for one year. The one-year recurrence rate, traditional chinese medicine (TCM) syndrome score, alpha-fetoprotein and child-pugh grade were compared between the two groups. The serum metabolites of the two groups before and after treatment were screened by ultra-high liquid chromatography-mass spectrometry technology, and the metabolic pathways and related biological pathways were analyzed. RESULTS: The one-year recurrence rate of the treatment group was significantly lower than that of the placebo group, and the overall improvement rate of TCM syndrome score was significantly better than that of the placebo group (P<0.05). There was no statistical significance in the comparison of alpha-fetoprotein and child-pugh grade between the two groups after treatment (P>0.05). Metabolomics results showed that there were 39 and 33 different metabolites in the treatment group before and after treatment and in the two groups after treatment, respectively. After enrichment analysis and topological analysis of the different metabolites, it was found that Fuzheng Xiaoliu Granules could affect amino acid metabolism, fatty acid metabolism and purine metabolism and other metabolic pathways. Before and after treatment in the treatment group and after treatment in the two groups, there were the same differential metabolites and metabolic pathways in the two comparison results. The same differential metabolites with FOLD CHANGE>1 include Stearic acid, Hypoxanthine, Kynurenic acid, Arachidonic acid, and N-Arachidonoyl Dopamine. The same metabolic pathways with Impact>0.1 include Arachidonic acid metabolism and Histidine metabolism. CONCLUSION: Fuzheng xiaoliu granules can effectively reduce the recurrence rate of stage II liver cancer patients after comprehensive intervention and improve the TCM syndrome. It may inhibit the activation of PI3K/Akt and ERK signaling pathways by regulating the content of metabolites involved in metabolic pathways such as amino acids and fatty acids, thereby delaying tumor recurrence.
3.Biological connotation of "phlegm-turbidity" theory in hepatocellular carcinoma microenvironment based on abnormal lipid metabolism
Fangming YANG ; Zhun XIAO ; Xiaoqi CHEN ; Chuanlei ZHANG ; Xinju CHEN ; Suping MA ; Wenxia ZHAO
Journal of Clinical Hepatology 2023;39(2):432-438
There is still a lack of effective strategies for the prevention and treatment of liver cancer, and a deep understanding of its pathogenesis may help to develop new treatment methods. Due to the abnormal changes of lipid metabolism in the development and progression of liver cancer, such process is closely associated with the "phlegm-turbidity" theory in traditional Chinese medicine (TCM). Starting from the changes of lipid metabolism in hepatocellular carcinoma microenvironment, this article discusses the association of the abnormal changes of lipid metabolism in tumor cells and immune cells with the "phlegm-turbidity" theory and the clinical efficacy of phlegm-eliminating therapies in clinical practice. Since the "phlegm-turbidity" theory in TCM plays an important role in the pathogenesis and pathological changes of liver cancer, the analysis of its theoretical connotation helps to clarify pathological mechanism, thereby providing a theoretical basis for the role of TCM in the prevention and treatment of liver cancer.