Anti-EDN1 monoclonal antibody, clone 2D20

Background: Infiltrating T-helper cells, cytotoxic T-cells, B-cells and monocytes are thought to mediate the damage to myelin, oligodendrocytes and axons in multiple sclerosis (MS), which results in progressive disability. Objective: The objective of this paper is to explore gene expression profiles of leukocytes in the cerebrospinal fluid (CSF) compartment of MS patients during relapse. Methods: Global gene expression was analyzed by DNA microarray analysis of cells in CSF from MS patients and controls, and verifications were performed with real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results: Fifty percent of the recently described risk genes for MS and 28% of non-risk genes were differently expressed in MS patients compared to controls (chi(2)-test, p=7.7 x 10(-5)). Genes involved in T-and NK-cell processes were up-regulated, and genes involved in processes targeting innate immunity or B-cells were down-regulated in MS. Increased expression of EDN1 and CXCL11 and decreased expression of HMOX1 was verified with real-time PCR and increased expression of CXCL13 was verified with ELISA in CSF. Conclusion: DNA microarray analysis is useful in identifying differently expressed genes in CSF leukocytes, which may be important in MS in vivo. Our findings suggest that many of the risk genes for MS are differently expressed in the disease-mediating leukocytes that penetrate the blood-brain barrier.

The identification of network targets is one of the core issues used to reveal the molecular mechanism of traditional Chinese medicine (TCM) and is also the grand challenge of modernization of TCM. In this study, a protein-protein interaction (PPI) network was constructed based on the integration of network pharmacology and metabolomics, which was used as an effective approach to elucidate the relationship between disease pathway proteins and the targets of active small-molecule compounds. The intermolecular transfer process of the drug effect of active compounds in Salvia miltiorrhiza (SM) was revealed and visualized using the PPI network. Our study indicates that PTGS2 was the most important disease protein regulated by the active compounds in SM. Furthermore, the drug targets that can be linked to PTGS2 were regarded as direct targets and the direct targets of the active compounds were identified, respectively. Western blot and co-immuno precipitation (Co-IP) were used to verify the results of the network analysis and reveal the intermolecular transfer process of the effect of Tan IIA. Biological validation revealed that Tan IIA-EDN1-PTGS2-anandamide was a major intervention way of Tan IIA on early atherosclerosis (AS). This work provides a new perspective for the discovery of drug targets and the specific approaches regulated by the active compounds in SM on disease pathway proteins, which is beneficial for understanding the mechanism of action of bioactive compounds and expanding their clinical applications.