Exploration of Simiao-Yongan Decoction on knee osteoarthritis based on network pharmacology and molecular docking.

Use network pharmacology combined with molecular docking to study the effects of Simiao-Yongan Decoction (SMYAD) intervenes in Knee Osteoarthritis (KOA) related targets and signaling pathways, and explores the molecular mechanism of SMYAD in treating KOA. The active ingredients and targets of SMYAD, which concluded 4 traditional Chinese medicines, were screened in TCMSP, and the related gene targets of KOA were screened in the disease databases GeneCards, MalaCards, DisGeNET, and Comparative Toxicogenomics Database, and their intersection data were obtained after integration. And used Cytoscape 3.9.1, the software topologies the network diagram of "compound-drug-active ingredient-target protein-disease." Obtains the protein-protein interaction network diagram through STRING, and enriches and analyzes the obtained core targets. Carry out molecular docking matching verification on the main active ingredients and key targets of the drug. 106 active ingredients and 175 targets were screened from SMYAD to intervene in KOA, 36 core targets were obtained through protein-protein interaction screening, and 10 key targets played an important role. The enrichment results showed that the biological process of gene ontology mainly involved positive regulation of gene expression, negative regulation of apoptosis process, and positive regulation of apoptosis process. KEGG signaling pathway mainly involves AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, hypoxia-inducible factor-1 signaling pathway, IL-17 signaling pathway. The pathway of Reactome mainly involves interleukin-4 and interleukin-13 signaling, cytokine signaling in immune system, immune system, apoptosis. Molecular docking showed that the mainly effective components of SMYAD can fully combine with TNF, IL1B, IL6, and CASP3. The results show that the main active ingredients and potential mechanism of action of SMYAD in the treatment of KOA have the characteristics of multiple targets and multiple pathways, which provides ideas and basis for further in-depth exploration of its specific mechanism.

Exploring the mechanism of Buyang Huanwu Decoction in the treatment of spinal cord injury based on network pharmacology and molecular docking.

Buyang Huanwu Decoction, a traditional Chinese medicine decoction, is widely used to treat spinal cord injury in China. However, the underlying mechanism of this decoction in treating spinal cord injury is unclear. This study used network pharmacology and molecular docking to examine the pharmacological mechanism of Buyang Huanwu Decoction in prevention and treatment of spinal cord injury. The active compounds and target genes of Buyang Huanwu Decoction were collected from the Traditional Chinese Medicine Systems Pharmacology and the SwissTargetPrediction Database. The network diagram of "traditional Chinese medicine compound target" was constructed by Cytoscape software. Genetic data of spinal cord injury were obtained by GeneCards database. According to the intersection of Buyang Huanwu Decoction's targets and disease targets, the core targets were searched. The protein-protein interaction network were constructed using the STRING and BisoGenet platforms. Meanwhile, gene ontology enrichment and Kyoto encyclopedia of genes, and genome pathway were performed on the intersection targets by Metascape. Molecular docking technology was adopted to verify the combination of main components and core targets. A total of 109 active compounds and 5440 prediction targets were screened from 7 Chinese herbal medicines of Buyang Huanwu Decoction, with 98 active components and 49 related prediction targets being strongly linked to Spinal Cord Injury. By studying protein-protein interaction network, a total of 8 core proteins were identified, primarily interleukin-6, tumor protein P53, epidermal growth factor receptor, and others. Positive regulation of kinase activity regulation of reaction to inorganic chemicals are the basic biological processes. Buyang Huanwu Decoction cures Spinal Cord Injury primarily by moderating immunological inflammation, apoptosis, and oxidative stress, which involves the cancer pathway, the HIF-1 signaling pathway, the p53 signaling pathway, the MAPK signaling pathway, and so on. The results of molecular docking demonstrated that the primary components could attach to the target protein effectively. Finally, the mechanism of Buyang Huanwu Decoction in the treatment of spinal cord injury through multicomponent, multitarget, and multichannel was deeply explored. And it offers new ideas and directions for future research on the mechanism of the treatment of spinal cord injury.

Elucidating the mechanism of Hongjinshen decoction in the treatment of pulmonary fibrosis based on network pharmacology and molecular docking.

BACKGROUND: To explore the mechanism of compound Hongginshen decoction in improving pulmonary fibrosis based on network pharmacology. METHODS: The active components and targets of ginseng and Salvia miltiorrhiza were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The chemical components of Rhodiola, Ophiopogon japonicus, and Dendrobium were screened using the Traditional Chinese Medicine Integrated Database (TCMID), and the target compounds were predicted by the Swisstargets method. The related target genes of pulmonary fiber (PF) were screened by the Genecards database and the National Center of Biotechnology Information (NCBI) database. The protein-protein interaction network was drawn using the string database and Cytoscape software, and the network topology was analyzed. Then, using R3.6.3 software, biological processes, molecular function, cell component enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out on the common targets of drugs and diseases. The network diagram of the "traditional Chinese medicine composition disease target" of Compound Hongginshen Decoction was constructed and analyzed with the software of Cytoscape 3.6.1. RESULTS: We identified 159 active components and 2820 targets in Compound Hongginshen Decoction, and 2680 targets in pulmonary fibrosis. A total of 343 common targets were obtained by the intersection of drug targets and disease targets. protein-protein interaction protein interaction network analysis showed that PIK3CA, PIK3R1, MAPK1, SRC, AKT1, and so on may be the core targets of the compound Hongjingshen recipe in the treatment of pulmonary fibrosis. Gene Ontology (GO) enrichment analysis identified 3463 items, and KEGG pathway enrichment analysis identified 181 related signaling pathways, including the PI3K-Akt signaling pathway, HCMV pathway, Hb pathway, PGs pathway, and KSHV signaling pathway. CONCLUSION: Compound Hongginshen Decoction has the characteristics of a multichannel and multitargeted effect in the treatment of pulmonary fibrosis. Radix Ophiopogonis and Dendrobium officinale play a key role in the treatment of pulmonary fibrosis. The whole compound prescription may play a therapeutic role by affecting cell metabolism, being anti-inflammatory, regulating the immune system, promoting angiogenesis, and improving anaerobic metabolism.

Combinatorial discovery of Mo-based polyoxometalate clusters for tumor photothermal therapy and normal cell protection.

Nanomaterials with multiple functions such as precision diagnosis, therapeutic efficacy and biosafety are attractive for tumor treatment but remain a technical challenge. In this study, molybdenum (Mo)-based polyoxometalate clusters (Mo-POM) with considerable photothermal conversion efficiency (∼56.6%) and high stability (>30 days) were prepared through a modification of the Folin-Ciocalteu method. These synthetic particles accumulated at the target site, and induced thermal ablation of the tumor following near infrared (NIR) absorption. Furthermore, the Mo-POM effectively scavenged reactive oxygen species (ROS) through charge transfer between Mo(vi) and Mo(v) states, thereby avoiding off-target effects on normal cells and improving the therapeutic efficiency both in vitro and in vivo. Therefore, for the first time, we prepared Mo-POM having two key functions, i.e., photothermal therapy (PTT) for cancer cells and protection of normal cells. These exceptional features may open up the exploration of Mo-POM as new tools for PTT against tumors in clinical applications.

Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1-MMP9 axis.

UNLABELLED: Cancer-associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer-associated MSCs (LC-MSCs) and hepatocellular carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC-MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC-MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC-MSCs compared with liver normal MSCs (LN-MSCs) from adjacent cancer-free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC-MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)-155 in HCC cells was significantly up-regulated by coculture with LC-MSCs and by S100A4 ectopic overexpression. The invasion-promoting effects of S100A4 were significantly attenuated by a miR-155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR-155 expression in HCC cells. We demonstrate that S100A4 secreted from LC-MSCs promotes the expression of miR-155, which mediates the down-regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. CONCLUSION: S100A4 secreted from LC-MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013).