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• Total of 46 HM-induced genes were identified as HM-stress response genes, including functional proteins and transcription factors. • Total of 12 DGEs related to HM-stress response was validated using quantitative RT-PCR. • Transcript of WRKY33, PIN1 protein, MRP protein and ABC transporter were found significantly increased after 24 h in the both material, contrary to ARF1 and ERF-rap2.7. • Transcript of LCC4, bHLH143 and GST were found significantly accumulated in the sensitive material 'Hongxin' than the resistant material 'XCB' at different time points (0 h, 12 h, 24 h, 36 h, 48 h and 72 h). • GO enrichment analysis showed that most of DEGs related to cellular response to stimulus, as well as response to stress. Heavy metals (HMs) are essential to plant life in suitable amounts, but cellular damage might be caused by excess amounts of HMs. In recent years, most reports on unique metal stresses, such as chromium (Cr), lead (Pb) and cadmium (Cd), have utilized radish, especially Liwang Liu's laboratory. However, major activated genes related to HM stress shared in Cr, Pb and Cd stress and their related specific pathways are urgently required in radish. Herein, according to FPKM for four transcriptomes collected from Liu's laboratory, 46 DEGs related to HM stress genes shared among heavy metal (Cr, Cd and Pb) treatments were identified, together with 66 HM-induced genes, comprising those for functional proteins and transcription factors (TFs). Of these genes, 12 DEGs related to the HM stress response were validated using quantitative real-time PCR. The results showed that WRKY33 was significantly changed in response to heavy metal stress (Cr, Cd and Pb) treatment after 24 h in both the sensitive material 'Hongxin 1' and the resistant material 'XCB'. Similar trends were also identified for transcripts of PIN1 protein, MRP protein and ABC transporter. Conversely, the transcripts of LCC4, bHLH143 and GST were found to be significantly changed in the sensitive material 'Hongxin 1' compared with the resistant material 'XCB' treated at different time points (0 h, 12 h, 24 h, 36 h, 48 h and 72 h). However, ARF1 and ERF-rap2.7 transcripts were found to be significantly decreased after 24 h of treatment in 'Xichangbai 1' compared with 'Hongxin 1' after heavy metal stress. In addition, most of the DEGs were found to be significantly enriched in the GO terms cellular response to extracellular stimulus, response to extracellular stimulus, auxin mediated signaling pathway, cellular response to chemical stimulus and response to oxidative stress through GO enrichment analysis. These results will expand our understanding of plant responsiveness to HM stress in radish under Cr, Pb and Cd stress and facilitate further genetic manipulation of HM stress genes on uptake and accumulation in radish. [ABSTRACT FROM AUTHOR]

• Carapa procera stem barks and leaves extracts were investigated. • Chemical characterization was examined by NMR and LC-MS techniques. • Stem bark extracts were more effective than leave extracts in antioxidant assays. • Bioinformatic analysis showed the interaction between main compounds and biological pathways. • The findings could provide a great starting point on novel applications by using C. procera. The methanolic and water extracts of Carapa procera leaves and stem barks were screened for their phytochemical content using a multi-technique approach. The extracts were also assessed for their in vitro antioxidant capacity along with their anti-diabetic (α-amylase, α-glucosidase), anti-tyrosinase, anti-elastase and anti-cholinesterase (AChE, BChE) activities. Furthermore, antibacterial and antifungal effects were determined against several bacterial and fungal strains. Data Integration Analysis for Biomarker discovery using Latent components (DIABLO) integrative analysis was conducted on collected data to determine the influence of extraction solvents and plant parts on phytochemical content, antioxidant properties and enzyme inhibitory properties of C. procera samples. Additionally, the major identified compounds were screened as modulators of multiple pathways involved in human diseases via Gene Ontology (GO) enrichment analysis. Results showed that methanolic stem bark extract exhibited the most potent ABTS scavenging, Cu2+ and Fe3+ reducing power, total antioxidant capacity and Fe2+ chelating power and displayed the highest total flavanol content. Methanolic extracts of leaves and stem barks were abounded with phenolics and had the greatest anti-AChE, anti-BChE, anti-tyrosinase and anti-elastase activities. A significant antifungal activity was observed, with the lowest minimum inhibitory concentration and minimum fungicidal values of 0.07 and 0.15 mg/mL, respectively. DIABLO integrative analysis suggested that the phytochemical content and biological activities varied significantly within the plant parts and were influenced by types of solvent used. GO enrichment analysis on the main bioactive compounds showed modulation of multiple pathways associated with cancer. Obtained results demonstrated that stem bark and leaves of C. procera can be considered as promising sources of bioactive molecules with high pharmacological values. [ABSTRACT FROM AUTHOR]

Purpose: To develop a comprehensive differential expression gene profile as well as a prediction model based on the expression analysis of pediatric sepsis specimens. Methods: In this study, compared with control specimens, a total of 708 differentially expressed genes in pediatric sepsis (case-control at a ratio of 1:3) were identified, including 507 up-regulated and 201 down-regulated ones. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes indicated the close interaction between neutrophil activation, neutrophil degranulation, hematopoietic cell lineage, Staphylococcus aureus infection, and periodontitis. Meanwhile, the results also suggested a significant difference for 16 kinds of immune cell compositions between two sample sets. The two potential selected biomarkers (MMP and MPO) had been validated in septic children patients by the ELISA method. Conclusion: This study identified two potential hub gene biomarkers and established a differentially expressed genes-based prediction model for pediatric sepsis, which provided a valuable reference for future clinical research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qiao, Zhang and Liu.)

Nowadays, cancer is considered one of the leading causes of death in developing countries. Due to mediocre socioeconomic status of many of the North African countries, people resort to traditional medicine from natural products for cancer therapy which are of great chemical complexity, interacting with several protein targets leading to synergistic effects. A holistic network pharmacology approach is needed for understanding the molecular mechanism of North African plants constituents in the different cancer-related pathways. The aim of this study is the implementation of network pharmacology for identification of the main active constituents of North African plants against cancer molecular targets and to explore their therapeutic mechanism. Constituents of North African plants were retrieved from public database and ADME screening was implemented for filtration of constituents using Qikprop software. STITCH database was used for predicting the plant constituents target proteins/genes, TDD DB and Uniprot databases were used for identifying genes related to cancer. Constituent-target gene (C-T), constituent-pathway (C-P) and plant-constituent-target gene (P-C-T) networks were constructed using Cytoscape to decipher the anti-cancer mechanism of action of the plants. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to cancer. 6844 constituent were subjected to ADME filtration resulting in 3194 constituent which were forwarded to target prediction. 53 constituents and 36 targets were linked through 329 edges which constituted the main pathways related to cancer. Luteolin, alternariol, apigenin, aloe-emodin and myricetin had the highest combined score in the C-T network, while the genes CASP3, CYP1A1, CYP1B1, PTGS2, MAPK8, AKT1 and EGFR were the most enriched by the constituents in this network. Euphorbia spp., Hyphaene thebaica , Artemisia herba-alba , bee propolis and Marrubium vulgare possessed the largest number of P-C-T interactions. The identified targets were mainly associated with cell cycle arrest and apoptosis in addition to inhibition of cellular proliferation by revealing a striking functional association with various signal and cancer related pathways Analysis of the constructed pharmacological networks results allowed for the prediction and interpretation of the multi-constituent, multi-target, and multi-pathway mechanisms of North African plants as potential source for supportive treatment of cancer where their potential molecular mechanism towards cancer-associated targets, biological processes and pathways were revealed. Image 1 [ABSTRACT FROM AUTHOR]

Xixiancao( Siegesbeckiae Herba) has the effect of treating ischemic stroke( IS),however,the mechanism has not been fully elucidated. In this study,combined with Lipinski's five principles and Veber oral bioavailability rules,68 chemical components of Xixiancao were obtained by database and literature search. Based on the reverse targeting,248 potential targets were obtained and mapped it to the ischemic stroke target set,47 potential targets for the treatment of ischemic stroke were obtained. Molecular docking technique was used to verify that the Xixiancao component has good binding activity to potential targets. GO enrichment analysis and pathway analysis were performed on potential targets using Clue GO. GO enrichment analysis showed that Xixiancao was mainly involved in life processes such as neuronal apoptosis,cholesterol storage and blood pressure regulation. Pathway analysis showed that Xixiancao may promote vascular repairing and regeneration by regulating the expression of ADAMTS1,FLT1 and KDR in VEGFA-VEGFR2 signaling pathway,activate cell survival signals and inhibit neuronal apoptosis by regulating the expression of CAMK2 AA,MDM2,MAPK1,MAPK3,CDK5 and MAPK10 in brain-derived neurotrophic factor signaling pathway and PI3 K-Akt signaling pathway. Lipid homeostasis and inflammation may also be regulated by Xixiancao through regulating the expression of ESR1,NR1 H3,PPARA,PPARG in the nuclear receptor signaling pathway. In addition,Xixiancao could also prevent platelet aggregation by regulating the expression of ITGA2 B,F2,F10,and ALB,and play an antithrombotic role. The results of this study indicate that Xixiancao plays an important role in the treatment of ischemic stroke mainly through anti-thrombosis,promoting angiogenesis,protecting neurons,anti-inflammatory and regulating blood pressure and lipids.

Tanshinone IIA (Tan IIA) is one of the major fat-soluble ingredients in Salvia miltiorrhiza which has been widely used for various inflammatory conditions associated with cardiovascular and cerebrovascular disorders. However, the underlying anti-inflammatory mechanisms of Tan IIA are incompletely understood. The purpose of this study was to illuminate the anti-inflammatory mechanism of Tan IIA based on the protein interaction network (PIN) analysis. A PIN of Tan IIA was constructed with 281 nodes and 814 interactions and analyzed by gene ontology (GO) enrichment analysis based on Markov Cluster algorithm (MCL). Three modules were associated with anti-inflammatory actions. The most interesting finding of this study was that the anti-inflammatory effect of Tan IIA may be partly attributable to the mediate activation of TRAF2, TRAF3 and TRAF6, to inhibit the toll-like receptor signaling pathway and combine with AGER. Therefore, the module-based network analysis approach will be a new method for better understanding the anti-inflammatory mechanism of Tan IIA.