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Objective To investigate the inhibitory effect of ginsenoside Rg3 combined with cisplatin (DDP) on DDP-resistant cell line SGC-7901/DDP and their molecular mechanism.Methods SGC-7901/DDP cells were divided into four groups including a control group,a ginsenoside Rg3 (40 μg/ml) treatment group,a DDP (1.40 μg/ml) treatment group,and a drug combination treatment group.The proliferation ability of SGC-7901/DDP cells was detected by MTT,EdU,and colony formation assays.The apoptosis ability of SGC-7901/DDP cell was detected by flow cytometry and Hoechst 33342 staining.The protein levels of apoptosis-related markers were detected by Western blotting.The migration ability of SGC-7901/DDP cells was detected by wound healing and Transwell assays.The expression levels of proteins in epithelial-mesenchymal transformation (EMT) and Wnt/β-catenin signaling pathway were determined by Western blotting and immunofluorescence staining.Results Compared with the ginsenoside Rg3 or the DDP treatment groups,the drug combination treatment group inhibited the proliferation ( t =8.062, P =0.001; t =7.090, P =0.002),colony formation ( t =8.062, P =0.001; t =6.144, P =0.004),and migration ( t =7.424, P =0.002; t =4.317, P =0.013),and promoted the apoptosis ( t =5.530, P =0.031; t =6.036, P =0.026) of SGC-7901/DDP cells.Compared with the ginsenoside Rg3 and the DDP treatment groups,the drug combination treatment group down-regulated the expression levels of EMT-associated proteins including vimentin ( t =24.450, P <0.001; t =14.750, P <0.001),Snail ( t =29.640, P <0.001; t =70.700, P <0.001),Slug ( t =89.230, P <0.001; t =87.360, P <0.001),matrix metalloproteinase (MMP) 2 ( t =84.540, P <0.001; t =67.120, P <0.001),and MMP9 ( t =19.010, P <0.001; t =10.890, P <0.001),as well as those of Wnt/β-catenin signaling pathway related proteins including Wnt ( t =35.480, P <0.001; t =14.670, P <0.001),β-catenin ( t =155.800, P <0.001; t =118.100, P <0.001),C-myc ( t =20.870, P <0.001; t =3.334, P =0.029),and cyclin D1 ( t =5.007, P =0.008; t =8.347, P =0.001).Meanwhile,it up-regulated the expression of epithelial cells including E-cadherin ( t =36.450, P <0.001; t =33.810, P <0.001) and ZO-1 ( t =37.060, P <0.001; t =37.030, P <0.001).Conclusion Ginsenoside Rg3 enhanced the sensitivity of SGC-7901/DDP cells to DDP by inhibiting the activity of Wnt/β-catenin signaling pathway.

Background: Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated., Methods: Here, to overcome the limitation of conventional network pharmacology methods with a weak combination with clinical information, this study proposes a network pharmacology approach of integrated bioinformatics that applies a weighted gene co-expression network analysis (WGCNA) to conventional network pharmacology, and then integrates molecular docking technology and biological experiments to verify the results of this network pharmacology analysis., Results: The WGCNA analysis revealed 2 gene modules closely associated with classification, staging and survival status of PC. Further CytoHubba analysis revealed 10 hub genes (NCAPG, BUB1, CDK1, TPX2, DLGAP5, INAVA, MST1R, TMPRSS4, TMEM92 and SFN) associated with the development of PC, and survival analysis found 5 genes (TSPOAP1, ADGRG6, GPR87, FAM111B and MMP28) associated with the prognosis and survival of PC. By integrating these results into the conventional network pharmacology study of CKI treating PC, we found that the mechanism of CKI for PC treatment was related to cell cycle, JAK-STAT, ErbB, PI3K-Akt and mTOR signalling pathways. Finally, we found that CDK1, JAK1, EGFR, MAPK1 and MAPK3 served as core genes regulated by CKI in PC treatment, and were further verified by molecular docking, cell proliferation assay, RT-qPCR and western blot analysis., Conclusions: Overall, this study suggests that the optimized network pharmacology approach is suitable to explore the molecular mechanism of CKI in the treatment of PC, which provides a reference for further investigating biomarkers for diagnosis and prognosis of PC and even the clinical rational application of CKI., (© 2021. The Author(s).)

Objective: To investigate the shared mechanisms of scutellarin in angina pectoris (AP) and ischemic stroke (IS) treatment., Methods: A network pharmacology approach was used to detect the potential mechanisms of scutellarin in AP and IS treatment by target prediction, protein-protein interaction (PPI) data collection, network construction, network analysis, and enrichment analysis. Furthermore, molecular docking simulation was employed to analyze the interaction between scutellarin and core targets., Results: Two networks were established, including a disease-target network and a PPI network of scutellarin targets against AP and IS. Network analysis showed that 14 targets, namely, AKT1, VEGFA, JUN, ALB, MTOR, ESR1, MAPK8, HSP90AA1, NOS3, SERPINE1, FGA, F2, FOXO3, and STAT1, might be the therapeutic targets of scutellarin in AP and IS. Among them, NOS3 and F2 were recognized as the core targets. Additionally, molecular docking simulation confifirmed that scutellarin exhibited a relatively high potential for binding to the active sites of NOS3 and F2. Furthermore, enrichment analysis indicated that scutellarin might exert a therapeutic role in both AP and IS by regulating several important pathways, such as coagulation cascades, mitogen-activated protein kinase (MAPK) signaling pathway, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, Toll-like receptor signaling pathway, hypoxia inducible factor-1 (HIF-1) signaling pathway, forkhead box O (FoxO) signaling pathway, tumor necrosis factor (TNF) signaling pathway, adipocytokine signaling pathway, insulin signaling pathway, insulin resistance, and estrogen signaling pathway., Conclusions: The shared underlying mechanisms of scutellarin on AP and IS treatment might be strongly associated with its vasorelaxant, anticoagulant, anti-inflammatory, and antioxidative effects as well as its effect on improving lipid metabolism.

Background: This study profiled the somatic genes mutations and the copy number variations (CNVs) in cerebrospinal fluid (CSF)-circulating tumor DNA (ctDNA) from patients with neoplastic meningitis (NM)., Methods: A total of 62 CSF ctDNA samples were collected from 58 NM patients for the next generation sequencing. The data were bioinformatically analyzed by (Database for Annotation, Visualization and Integrated Discovery) DAVID software., Results: The most common mutated gene was TP53 (54/62; 87.10%), followed by EGFR (44/62; 70.97%), PTEN (39/62; 62.90%), CDKN2A (32/62; 51.61%), APC (27/62: 43.55%), TET2 (27/62; 43.55%), GNAQ (18/62; 29.03%), NOTCH1 (17/62; 27.42%), VHL (17/62; 27.42%), FLT3 (16/62; 25.81%), PTCH1 (15/62; 24.19%), BRCA2 (13/62; 20.97%), KDR (10/62; 16.13%), KIT (9/62; 14.52%), MLH1 (9/62; 14.52%), ATM (8/62; 12.90%), CBL (8/62; 12.90%), and DNMT3A (7/62; 11.29%). The mutated genes were enriched in the PI3K-Akt signaling pathway by the KEGG pathway analysis. Furthermore, the CNVs of these genes were also identified in these 62 samples. The mutated genes in CSF samples receiving intrathecal chemotherapy and systemic therapy were enriched in the ERK1/2 signaling pathway., Conclusions: This study identified genes mutations in all CSF ctDNA samples, indicating that these mutated genes may be acted as a kind of biomarker for diagnosis of NM, and these mutated genes may affect meningeal metastasis through PI3K-Akt signaling pathway.

Studying the changes of land use and its impacts on ecological condition in coastal areas is of great significance for understanding the evolution of the regional ecological conditions and even global change. In this study, the study area encompassed 10 provincial administrative units of China's coastal areas, covering a total of 56 cities. Based on the land use and land cover data in 1980, 1990, 1995, 2000, 2005, 2010 and 2015 and the corresponding elevation data, we assessed ecological conditions and its temporal dynamic evolution and spatial differentiation characteristics with the ecological grade index method. The effects of the elevation differentiation and land-sea gradient on the ecological condition in China's coastal areas were analyzed. The results showed that the ecological conditions of China's coastal areas were basically stable and deteriorated on the whole although partially improved from 1980 to 2015. With Hangzhou Bay as a boundary-belt, ecological conditions in southern parts were better than that in the northern parts. The ecological grade index differed significantly with the variation of elevation. The areas with elevation below 10 m were in rela-tively poor ecological condition, and the regions below 30 m had the most obvious changes of ecological conditions. Moreover, the ecological conditions increased with elevation, with a gradual turnaround trend of improvement at above 400 m. There was a gradient characteristic of the ecological grade index in China's coastal areas, showing a high-low-high pattern from land to sea. Furthermore, the maximum value of ecological condition changes appeared at a distance of 10 km to the coastline, and the values decreased with the increasing of distance to the coastline.