Network pharmacology and experimental verification of the potential mechanism of Er-Xian decoction in aplastic anemia.

To investigate the potential mechanism of Er-Xian decoction (EXD) in treating aplastic anemia (AA), the active components of EXD were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the targets of the components were predicted by the Swiss Target Prediction database. AA targets were collected from the GeneCards, OMIM, DisGeNET, PharmGKB, DrugBank, and TTD databases, the intersection of AA targets and EXD targets was calculated, and an herb-component-target network was constructed by Cytoscape 3.7.2 software. The STRING database was used for protein‒protein interaction (PPI) analysis, and Cytoscape 3.7.2 software was used to construct a PPI network and perform topology analysis. The core targets were imported into the DAVID database for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The molecular docking software AutoDock was used to measure the affinity between active components and key targets. Finally, we established a mouse model of AA and verified the key targets and signaling pathways of EXD by RT‒PCR, ELISA and Western blot analysis. A total of 53 active components were screened from EXD, 2516 AA-related targets were collected, and 195 common targets were obtained. An herb-component-target network and a PPI network were successfully constructed, and 36 core targets were selected from the PPI network. The main active components of EXD include luteolin, kaempferol, berberine, etc., and key targets include PIK3CA, AKT1, STAT3, etc. GO functional enrichment analysis showed that cell components, molecular functions and biological processes with significant correlations were macromolecular complexes, protein serine/threonine/tyrosine kinase activity and protein phosphorylation, respectively. KEGG pathway analysis showed that the pathways with significant correlations included the PI3K-Akt signaling pathway and JAK-STAT signaling pathway. Molecular docking results showed that the tested key targets had good affinity for the corresponding active components. In AA mice, we found that EXD significantly increased white blood cell count, red blood cell count, platelet count and hemoglobin levels, increased mRNA levels of PIK3CA, PIK3CD, AKT1, JAK2, STAT3 and MAPK1, and promoted phosphorylation of PI3K, AKT, ERK1/2 and STAT3. In summary, EXD acts on PI3K, AKT, STAT3 and other targets through berberine, luteolin, quercetin and other components to regulate the PI3K-Akt pathway, JAK-STAT pathway and other pathways, thus exerting its therapeutic effect on AA. This study explained the Chinese medicine theory of treating AA with EXD by tonifying kidney-yang and provides a scientific basis for the use of EXD in treating AA.

Clinical significance of changes in tumor markers, extracellular matrix, MMP-9 and VEGF in patients with gastric carcinoma.

BACKGROUND/AIMS: The aim of this study was to evaluate the prognostic significance of some serum tumor marker level, extracellular matrix (ECM), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) in patients with gastric cancer. METHODOLOGY: The serum tumor markers included CEA, CA50 and CA19-9, ECM included laminin (LN), hyaluronic acid (HA), and collagen type III and IV were measured in 40 patients with gastric carcinoma and 20 matched healthy controls by radioimmunoassay. MMP-9, VEGF and MVD were measured with immunohistochemical methods and the computer image analyzer. Microvascular density (MVD) in tissues of patients with gastric carcinoma was detected. RESULTS: The levels of CEA, CA50, CA19-9, HA, LN and collagen type IV in the patients with metastasis were significantly higher than those in the patients without metastasis (p < 0.05). The expression of MMP-9 and collage type IV in the patients with metastasis and poorly differentiated carcinomas were significantly higher than those in the patients without metastasis whose tumors were well/moderately differentiated (p < 0.05). CONCLUSIONS: CEA, CA50, CA19-9, HA, LN and collagen type IV levels can be used as a signal of metastasis and disease progression in patients with gastric carcinoma. When a gastric carcinoma expresses a high level of MMP-9 and VEGF with high MVD, the power of infiltration and metastasis of the gastric carcinoma is enhanced.

Effect of sea buckthorn on liver fibrosis: a clinical study.

AIM: To appraise the effect of sea buckthorn (Hippophae rhamnoides) on cirrhotic patients. METHODS: Fifty cirrhotic patients of Child-Pugh grade A and B were randomly divided into two groups: Group A as the treated group (n=30), taking orally the sea buckthorn extract, 15 g 3 times a day for 6 months. Group B as the control group (n=18), taking vitamin B complex one tablet, 3 times a day for 6 months. The following tests were performed before and after the treatment in both groups to determine LN, HA, collagens types III and IV, cytokines IL-6 and TNFalpha, liver serum albumin, total bile acid, ALT, AST and prothrombin time. RESULTS: The serum levels of TNFalpha, IL-6, laminin and type IV collagen in group A were significantly higher than those in the control group. After a course of sea buckthorn treatment, the serum levels of LN, HA, collagen types III and IV, total bile acid (TBA) decreased significantly as compared with those before and after treatment in the control group. The sea buckthorn notably shortened the duration for normalization of aminotransferases. CONCLUSION: Sea buckthorn may be a hopeful drug for prevention and treatment of liver fibrosis.