Exploring the possible molecular targeting mechanism of Saussurea involucrata in the treatment of COVID-19 based on bioinformatics and network pharmacology.

OBJECTIVE: Based on bioinformatics and network pharmacology, the treatment of Saussurea involucrata (SAIN) on novel coronavirus (COVID-19) was evaluated by the GEO clinical sample gene difference analysis, compound-target molecular docking, and molecular dynamics simulation. role in the discovery of new targets for the prevention or treatment of COVID-19, to better serve the discovery and clinical application of new drugs. MATERIALS AND METHODS: Taking the Traditional Chinese Medicine System Pharmacology Database (TCMSP) as the starting point for the preliminary selection of compounds and targets, we used tools such as Cytoscape 3.8.0, TBtools 1.098, AutoDock vina, R 4.0.2, PyMol, and GROMACS to analyze the compounds of SAIN and targets were initially screened. To further screen the active ingredients and targets, we carried out genetic difference analysis (n = 72) through clinical samples of COVID-19 derived from GEO and carried out biological process (BP) analysis on these screened targets (P ≤ 0.05)., gene = 9), KEGG pathway analysis (FDR≤0.05, gene = 9), protein interaction network (PPI) analysis (gene = 9), and compounds-target-pathway network analysis (gene = 9), to obtain the target Point-regulated biological processes, disease pathways, and compounds-target-pathway relationships. Through the precise molecular docking between the compounds and the targets, we further screened SAIN's active ingredients (Affinity ≤ -7.2 kcal/mol) targets and visualized the data. After that, we performed molecular dynamics simulations and consulted a large number of related Validation of the results in the literature. RESULTS: Through the screening, analysis, and verification of the data, it was finally confirmed that there are five main active ingredients in SAIN, which are Quercitrin, Rutin, Caffeic acid, Jaceosidin, and Beta-sitosterol, and mainly act on five targets. These targets mainly regulate Tuberculosis, TNF signaling pathway, Alzheimer's disease, Pertussis, Toll-like receptor signaling pathway, Influenza A, Non-alcoholic fatty liver disease (NAFLD), Neuroactive ligand-receptor interaction, Complement and coagulation cascades, Fructose and mannose metabolism, and Metabolic pathways, play a role in preventing or treating COVID-19. Molecular dynamics simulation results show that the four active ingredients of SAIN, Quercitrin, Rutin, Caffeic acid, and Jaceosidin, act on the four target proteins of COVID-19, AKR1B1, C5AR1, GSK3B, and IL1B to form complexes that can be very stable in the human environment. Tertiary structure exists. CONCLUSION: Our study successfully explained the effective mechanism of SAIN in improving COVID-19, and at the same time predicted the potential targets of SAIN in the treatment of COVID-19, AKR1B1, IL1B, and GSK3B. It provides a new basis and provides great support for subsequent research on COVID-19.

A randomized, controlled phase II trial of maxillofacial and oral massage in attenuating severe radiotherapy-induced oral mucositis and lipid metabolite changes in nasopharyngeal carcinoma.

PURPOSE: This randomized controlled phase II study investigated the efficacy, safety and underlying mechanism of maxillofacial and oral massage (MOM) in nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy. METHODS: A total of 158 NPC patients were randomly assigned 1:1 to routine oral care and medication (the control group) or that with additional MOM (the treatment group). The primary endpoint was the incidence of severe radiotherapy-induced oral mucositis (SRTOM). In addition, the time of initiation and duration of RTOM and SRTOM, adverse events, dynamic changes of lipid metabolites in peripheral blood were analyzed. RESULTS: Seventy-six patients in the treatment group and seventy-nine in the control group completed the trial. The incidence of SRTOM in the treatment group was lower than the control (26.3% vs. 46.8%, P = 0.008). The median initiation time to RTOM and SRTOM was significantly longer in the treatment group than the control (RTOM:12 vs 10 days, hazard ratio [HR] 0.52, P < 0.001; SRTOM: 28.5 vs 19 days, HR 0.5579, P = 0.002). While the median duration time of RTOM and SRTOM in the treatment group was shorter (RTOM: 20.7 vs 24.7 days, P = 0.001; SRTOM: 8.05 vs 13.08 days, P < 0.001). Only 1.3% of patients obtained grade 3 or higher adverse events during MOM. The anti-inflammatory lipids increased significantly after MOM, especially with 10.6 Gy or higher. CONCLUSION: MOM significantly attenuated the incidence of SRTOM in NPC patients. The adverse events of MOM were slight and tolerant. MOM enhanced anti-inflammatory lipid metabolites, which might be an underlying mechanism.

[Construction of a bivalent plant expression vector carrying VvSUC11 and VvSUC12 genes and its genetic transformation in sugar beet].

We have recombined genes VvSUC11, VvSUC12 from Vitis vinifera L., and root-specific promoters of sweet potato storage protein gene from Ipomoea batatas L. Lam., named as SP1 and SP2. We have constructed a vector pCAMBIA2301-SP1- VvSUC11-SP2-VvSUC12 using pCAMBIA2301 as an original vector. VvSUC11 and VvSUC12 were under the control of root-specific promoters of sweet potato storage protein gene. We transformed the vector into KWS-9103 breeding line of Beta vulgaris L. with Agrobacterium-mediated transformation. We have established the optimal genetic transformation protocol of sugar beet as following: the explants pre-cultured for 4 days were immersed in Agrobacterium suspension of OD(600)=0.5, supplemented with 0.005% Silwet L-77, and followed by a 4-day culture on medium containing cefotaxime, then the buds were selected on medium containing kanamycin and cefotaxime. The percentage of kanamycin-resistant buds was as high as 42%. Results of PCR and RT-PCR proved that the target genes had integrated into sugar beet genome and expressed. It will lay a foundation for further studying their function in Beta vulgaris.