Characterization and Significance of Monocytes in Acute Stanford Type B Aortic Dissection
JOURNAL OF IMMUNOLOGY RESEARCH
Authors: Lu, Li; Tong, Yuanhao; Wang, Wenwen; Hou, Yayi; Dou, Huan; Liu, Zhao
Abstract
Acute aortic dissection (AAD) is one of the most common fatal diseases noted in vascular surgery. Human monocytes circulate in dynamic equilibrium and display a considerable heterogeneity. However, the role of monocytes in AAD remains elusive. In our recent study, we firstly obtained blood samples from 22 patients with Stanford type B AAD and 44 age-, sex-, and comorbidity-matched control subjects. And the monocyte proportions were evaluated by flow cytometry. Results showed that the percentage of total CD14(+) monocytes in the blood samples of Stanford AAD patients was increased significantly compared with that of normal volunteers (P<0.0005), and the absolute numbers of CD14(bright)CD16(+) and CD14(bright)CD16(-) monocytes both increased significantly regardless of the percentage of PBMC or CD14(+) cells, while CD14(dim)CD16(+) monocytes displayed the opposite tendency. However, the percentage of CD14(+) cells and its three subsets demonstrated no correlation with D-dimer (DD) and C-reactive protein (CRP). Then, blood mononuclear cell (PBMC) samples were collected by Ficoll density gradient centrifugation, followed with CD14(+) magnetic bead sorting. After the purity of CD14(+) cells was validated over 90%, AAD-related genes were concentrated in CD14(+) monocytes. There were no significant differences observed with regard to the mRNA expression levels of MMP1 (P=0.0946), MMP2 (P=0.3941), MMP9 (P=0.2919), IL-6 (P=0.4223), and IL-10 (P=0.3375) of the CD14(+) monocytes in Stanford type B AAD patients compared with those of normal volunteers. The expression levels of IL-17 (P<0.05) was higher in Stanford type B AAD patients, while the expression levels of TIMP1(P<0.05), TIMP2(P<0.01), TGF-beta 1 (P<0.01), SMAD3 (P<0.01), ACTA2 (P<0.001), and ADAMTS-1 (P<0.001) decreased. The data suggested that monocytes might play an important role in the development of Stanford type B AAD. Understanding of the production, differentiation, and function of monocyte subsets might dictate future therapeutic avenues for Stanford type B AAD treatment and can aid the identification of novel biomarkers or potential therapeutic targets for decreasing inflammation in AAD.
Chinese Dragon's Blood EtOAc Extract Inhibits Liver Cancer Growth Through Downregulation of Smad3
FRONTIERS IN PHARMACOLOGY
Authors: Chen, Xiaonan; Zhao, Yanan; Yang, Ailin; Tian, Yingying; Pang, Daoran; Sun, Jing; Tang, Leimengyuan; Huang, Huiming; Wang, Ying; Zhao, Yunfang; Tu, Pengfei; Hu, Zhongdong; Li, Jun
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies, which ranks the third leading cause of cancer-related death worldwide. The screening of anti-HCC drug with high efficiency and low toxicity from traditional Chinese medicine (TCM) has attracted more and more attention. As a TCM, Chinese dragon's blood has been used for the treatment of cardiovascular illness, gynecological illness, skin disorder, otorhinolaryngological illness, and diabetes mellitus complications for many years. However, the anti-tumor effect and underlying mechanisms of Chinese dragon's blood remain ill-defined. Herein we have revealed that Chinese dragon's blood EtOAc extract (CDBEE) obviously suppressed the growth of human hepatoma HepG2 and SK-HEP-1 cells. Moreover, CDBEE inhibited the migration and invasion of HepG2 and SK-HEP-1 cells. Additionally, CDBEE displayed good in vitro anti-angiogenic activity. Importantly, CDBEE treatment significantly blunted the oncogenic capability of HepG2 cells in nude mice. Mechanistically, CDBEE inhibited Smad3 expression in human hepatoma cells and tumor tissues from nude mice. Using RNA interference, we demonstrated that CDBEE exerted anti-hepatoma activity partially through down-regulation of Smad3, one of major members in TGF-beta/Smad signaling pathway. Therefore, CDBEE may be a promising candidate drug for HCC treatment, especially for liver cancer with aberrant TGF-beta/Smad signaling pathway.