https://doi.org/10.1016/j.compbiomed.2022.105549

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

Network pharmacology and molecular docking approaches to elucidate the potential compounds and targets of Saeng-Ji-Hwang-Ko for treatment of type 2 diabetes mellitus

Potassium (K+) is essential for plant growth and stress responses. A deficiency in soil K+ contents can result in decreased wheat quality and productivity. Thus, clarifying the molecular mechanism underlying wheat responses to low-K+ (LK) stress is critical. In this study, a tandem mass tag (TMT)-based quantitative proteomic analysis was performed to investigate the differentially abundant proteins (DAPs) in roots of the LK-tolerant wheat cultivar “KN9204” at the seedling stage after exposure to LK stress. A total of 104 DAPs were identified in the LK-treated roots. The DAPs related to carbohydrate and energy metabolism, transport, stress responses and defense, and post-translational modifications under LK conditions were highlighted. We identified a high-affinity potassium transporter (TaHAK1-4A) that was significantly up-regulated after the LK treatment. Additionally, TaHAK1-4A was mainly expressed in roots, and the encoded protein was localized in the plasma membrane. The complementation assay in yeast suggested that TaHAK1-4A mediates K+ uptake under extreme LK conditions. The overexpression of TaHAK1-4A increased the fresh weight and root length of Arabidopsis under LK conditions and improved the growth of Arabidopsis athak5 mutant seedlings, which grow poorly under LK conditions. Moreover, silencing of TaHAK1-4A in wheat roots treated with LK stress decreased the root length, dry weight, K+ concentration, and K+ influx. Accordingly, TaHAK1-4A is important for the uptake of K+ by roots exposed to LK stress. Our results reveal the protein metabolic changes in wheat induced by LK stress. Furthermore, we identified a candidate gene potentially relevant for developing wheat lines with increased K+ use efficiency.

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Proteomic Analysis of Roots Response to Potassium Deficiency and the Effect of TaHAK1-4A on K+ Uptake in Wheat

With no prominent treatment for pancreatic ductal adenocarcinoma (PDAC) in conventional chemotherapy, recent studies have focused on uniting conventional and traditional medicines including plant phytoconstituents. Herein, we used pharmacoinformatic studies to identify potent phytoconstituent as ligand having inhibition activities against canonical anticancer targets, and evaluated its effect on PDAC cell lines. SwissTargetPrediction and SuperPred tools were utilized to segregate protein targets of ligand in humans, following which FunRich was applied to garner its targets in PDAC. STRING analysis predicted protein-protein interactions and dynamic simulation studies confirmed stability of ligand-protein complex. For in vitro cytotoxic potential, ligand treatment at different concentrations was given to PDAC cell lines both alone and combined with gemcitabine, followed by evaluation of effects on migration. Differential gene expression was checked using PCR for evaluating mechanism of cytotoxicity. Results showed pentagalloylglucose (PGG) with highest docking and MMGBSA scores for Cyclooxygenase 2 (Cox2) inhibition site. SwissTargetPrediction and SuperPred analysis detected 40 targets of PGG in PDAC. Simulation data showed stability of protein-ligand complex. In in vitro experiments Mia-PaCa-2 was more sensitive to PGG than Panc-1. PGG successfully inhibited migration both alone and in combination with gemcitabine. Additionally, PGG treatment induced apoptosis in both the cell lines; but showed antagonism when combined with gemcitabine. In conclusion, our report demonstrates PGG has good binding with Cox2 and showed anti-PDAC activity by inhibiting migration and inducing apoptosis, thus it can be used as a therapy option. But further studies are required to confirm its behaviour as a combination therapy drug.Communicated by Ramaswamy H. Sarma.

Pharmacoinformatic screening of phytoconstituent and evaluation of its anti-PDAC effect using in vitro studies.

Evolutionary Aspects of the Fructan Syndrome

In some plants, sucrose: sucrose 1-fructosyltransferase (1-SST) is the first irreversible key enzyme in fructan biosynthesis. Studies have shown that fructan accumulation enhances abiotic stress tolerance of plants. To investigate the role of 1-SST in drought stress responses, a total of 37 cotton plants expressing a 1-SST gene from Allium cepa were developed by Agrobacterium-mediated transformation. Under drought stress in the field, compared with wild-type, ectopic expression of Ac1-SST in cotton resulted in significantly higher soluble sugars (especially 1-kestose), proline and relative water contents, as well as decreased malondialdehyde content, which contributed to maintaining intracellular osmoregulation and reducing membrane damage. In addition, ectopic expression of Ac1-SST in cotton significantly improved the photosynthesis rate, performance of PSII (including Pn, Fv/Fm, WUE, ΦPSII, and PItotal) and plant growth under drought stress. Furthermore, compared with the wild-type, under the droughted field, the yield loss per square meter of transgenic cotton was reduced by an average of 20.9% over two consecutive years. Our results indicate that the Ac1-SST gene can be used to improve drought tolerance and yield of cotton varieties, and might also be a promising drought-resistant gene for improving other crop varieties.

Ectopic Expression of the Allium cepa 1-SST Gene in Cotton Improves Drought Tolerance and Yield Under Drought Stress in the Field

Saussurea involucrata (SAIN), also known as Snow lotus (SI), is mainly distributed in high-altitude areas such as Tibet and Xinjiang in China. To identify novel targets for the prevention or treatment of lung adenocarcinoma and lung squamous cell carcinoma (LUAD&LUSC), and to facilitate better alternative new drug discovery as well as clinical application services, the therapeutic effects of SAIN on LUAD&LUSC were evaluated by gene differential analysis of clinical samples, compound target molecular docking, and GROMACS molecular dynamics simulation.Through data screening, alignment, analysis, and validation it was confirmed that three of the major active ingredients in SAIN, namely quercetin (Q), luteolin (L), and kaempferol (K), mainly act on six protein targets, which mainly regulate signaling pathways in cancer, transcriptional misregulation in cancer, EGFR tyrosine kinase inhibitor resistance, adherens junction, IL-17 signaling pathway, melanoma, and non-small cell lung cancer. In addition, microRNAs in cancer exert preventive or therapeutic effects on LUAD&LUSC. Molecular dynamics (MD) simulations of Q, L, or K in complex with EGFR, MET, MMP1, or MMP3 revealed the presence of Q in a very stable tertiary structure in the human body.There are three active compounds of Q, L, and K in SAIN, which play a role in the treatment and prevention of non-small cell lung cancer (NSCLC) by directly or indirectly regulating the expression of genes such as MMP1, MMP3, and EGFR. 

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Screening the components of Saussurea involucrata for novel targets for the treatment of NSCLC using network pharmacology

Fructose-1,6-biphosphate aldolase (FBA) is a multifunctional enzyme in plants, which participates in the process of Calvin-Benson cycle, glycolysis and gluconeogenesis. Despite the importance of FBA genes in regulating plant growth, development and abiotic stress responses, little is known about their roles in cotton. In the present study, we performed a genome-wide identification and characterization of FBAs in Gossypium hirsutum. Totally seventeen GhFBA genes were identified. According to the analysis of functional domain, phylogenetic relationship, and gene structure, GhFBA genes were classified into two subgroups. Furthermore, nine GhFBAs were predicted to be in chloroplast and eight were located in cytoplasm. Moreover, the promoter prediction showed a variety of abiotic stresses and phytohormone related cis-acting elements exist in the 2k up-stream region of GhFBA. And the evolutionary characteristics of cotton FBA genes were clearly presented by synteny analysis. Moreover, the results of transcriptome and qRT-PCR analysis showed that the expression of GhFBAs were related to the tissue distribution, and further analysis suggested that GhFBAs could respond to various abiotic stress and phytohormonal treatments. Overall, our systematic analysis of GhFBA genes would not only provide a basis for the understanding of the evolution of GhFBAs, but also found a foundation for the further function analysis of GhFBAs to improve cotton yield and environmental adaptability.

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Zhong-Qing Li

Papers

Ectopic Expression of the Allium cepa 1-SST Gene in Cotton Improves Drought Tolerance and Yield Under Drought Stress in the Field

Screening the components of Saussurea involucrata for novel targets for the treatment of NSCLC using network pharmacology

Genome-Wide Characterization and Expression Analysis Provide Basis to the Biological Function of Cotton FBA Genes.