Exogenous MgH2-derived hydrogen alleviates cadmium toxicity through m6A RNA methylation in rice.

Cadmium (Cd) contamination poses a substantial threat to crop yields and human health. While magnesium hydride (MgH2) has been reported as a hydrogen (H2) donor that promotes plant growth under heavy metal contamination, its role in rice remains elusive. Herein, seedlings of Oryza sativa L. Japonica variety Zhonghua 11 (ZH11) were selected and exposed to 20 µL of 1-mol/L cadmium chloride (CdCl2) solution via hydroponics to simulate Cd stress. Meanwhile, 0.1 mg of MgH2 was used to slow-release H2 to the experimental group to explore its potential effects on rice over a 2-week period. The results indicated that Cd exposure severely inhibited the growth and development of ZH11 rice seedlings. However, the exogenous slow-release of H2 from MgH2 effectively mitigated this inhibitory effect by restoring the balance of reactive oxygen species (ROS), maintaining endogenous H2 homeostasis, and supporting the photosynthetic system. High-performance liquid chromatography analysis revealed that exogenous H2 reduces m6A RNA methylation levels in mRNA under Cd stress. Consequently, MeRIP-seq was conducted to investigate the effect of Cd exposure in rice in the presence and absence of H2. The m6A modifications were enriched at the start codon, stop codon, and 3' UTR. By integrating RNA-seq data, 118 transcripts were identified as differentially methylated and expressed genes under Cd stress. These gene annotations were associated with ROS, biological stress, and hormonal responses. Notably, 297 differentially methylated and expressed genes were identified under Cd stress in the presence of H2, linked to heavy metals, protein kinases, and calcium signaling regulation. Cd strongly activates the MAPK pathway in response to stress. Exogenous H2 reduces Cd accumulation as well as enhances plant tolerance and homeostasis by lowering m6A levels, thereby decreasing the mRNA stability of these genes. Our findings indicate that MgH2, by supplying H2, regulates gene expression through m6A RNA methylation and confers Cd tolerance in rice. This study provides potential candidate genes for studying the remediation of heavy metal pollution in plants.

Seed priming with graphene oxide improves salinity tolerance and increases productivity of peanut through modulating multiple physiological processes.

Graphene oxide (GO), beyond its specialized industrial applications, is rapidly gaining prominence as a nanomaterial for modern agriculture. However, its specific effects on seed priming for salinity tolerance and yield formation in crops remain elusive. Under both pot-grown and field-grown conditions, this study combined physiological indices with transcriptomics and metabolomics to investigate how GO affects seed germination, seedling salinity tolerance, and peanut pod yield. Peanut seeds were firstly treated with 400 mg L⁻¹ GO (termed GO priming). At seed germination stage, GO-primed seeds exhibited higher germination rate and percentage of seeds with radicals breaking through the testa. Meanwhile, omics analyses revealed significant enrichment in pathways associated with carbon and nitrogen metabolisms in GO-primed seeds. At seedling stage, GO priming contributed to strengthening plant growth, enhancing photosynthesis, maintaining the integrity of plasma membrane, and promoting the nutrient accumulation in peanut seedlings under 200 mM NaCl stress. Moreover, GO priming increased the activities of antioxidant enzymes, along with reduced the accumulation of reactive oxygen species (ROS) in response to salinity stress. Furthermore, the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) of peanut seedlings under GO priming were mainly related to photosynthesis, phytohormones, antioxidant system, and carbon and nitrogen metabolisms in response to soil salinity. At maturity, GO priming showed an average increase in peanut pod yield by 12.91% compared with non-primed control. Collectively, our findings demonstrated that GO plays distinguish roles in enhancing seed germination, mitigating salinity stress, and boosting pod yield in peanut plants via modulating multiple physiological processes.

AaMYC3 bridges the regulation of glandular trichome density and artemisinin biosynthesis in Artemisia annua.

Artemisinin, the well-known natural product for treating malaria, is biosynthesised and stored in the glandular-secreting trichomes (GSTs) of Artemisia annua. While numerous efforts have clarified artemisinin metabolism and regulation, the molecular association between artemisinin biosynthesis and GST development remains elusive. Here, we identified AaMYC3, a bHLH transcription factor of A. annua, induced by jasmonic acid (JA), which simultaneously regulates GST density and artemisinin biosynthesis. Overexpressing AaMYC3 led to a substantial increase in GST density and artemisinin accumulation. Conversely, in the RNAi-AaMYC3 lines, both GST density and artemisinin content were markedly reduced. Through RNA-seq and analyses conducted both in vivo and in vitro, AaMYC3 not only directly activates AaHD1 transcription, initiating GST development, but also up-regulates the expression of artemisinin biosynthetic genes, including CYP71AV1 and ALDH1, thereby promoting artemisinin production. Furthermore, AaMYC3 acts as a co-activator, interacting with AabHLH1 and AabHLH113, to trigger the transcription of two crucial enzymes in the artemisinin biosynthesis pathway, ADS and DBR2, ultimately boosting yield. Our findings highlight a critical connection between GST initiation and artemisinin biosynthesis in A. annua, providing a new target for molecular design breeding of traditional Chinese medicine.

Mechanism of Lian Hua Qing Wen capsules regulates the inflammatory response caused by M1 macrophage based on cellular experiments and computer simulations.

PURPOSE: The polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M1 macrophages by cellular experiments and computer simulations. METHODS: This study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M1 macrophages (Induction of THP-1 cells into M1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets. RESULTS: Macrophages had 140,690 gene targets, inflammatory response had 12,192 gene targets, intersection gene targets were 11,772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action. CONCLUSION: In this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response.

A putative Na+/H+ antiporter BpSOS1 contributes to salt tolerance in birch.

White birch (Betula platyphylla Suk.) is an important pioneer tree which plays a critical role in maintaining ecosystem stability and forest regeneration. The growth of birch is dramatically inhibited by salt stress, especially the root inhibition. Salt Overly Sensitive 1 (SOS1) is the only extensively characterized Na+ efflux transporter in multiple plant species. The salt-hypersensitive mutant, sos1, display significant inhibition of root growth by NaCl. However, the role of SOS1 in birch responses to salt stress remains unclear. Here, we characterized a putative Na+/H+ antiporter BpSOS1 in birch and generated the loss-of-function mutants of the birch BpSOS1 by CRISPR/Cas9 approach. The bpsos1 mutant exhibit exceptional increased salt sensitivity which links to excessive Na+ accumulation in root, stem and old leaves. We observed a dramatic reduction of K+ contents in leaves of the bpsos1 mutant plants under salt stress. Furthermore, the Na+/K+ ratio of roots and leaves is significant higher in the bpsos1 mutants than the wild-type plants under salt stress. The ability of Na+ efflux in the root meristem zone is found to be impaired which might result the imbalance of Na+ and K+ in the bpsos1 mutants. Our findings indicate that the Na+/H+ exchanger BpSOS1 plays a critical role in birch salt tolerance by maintaining Na+ homeostasis and provide evidence for molecular breeding to improve salt tolerance in birch and other trees.

Rapamycin improves the survival of epilepsy model cells by blocking phosphorylation of mTOR base on computer simulations and cellular experiments.

PURPOSE: Epilepsy is a chronic brain dysfunction characterized by recurrent epileptic seizures. Rapamycin is a naturally occurring macrolide from Streptomyces hygroscopicus, and rapamycin may provide a protective effect on the nervous system by affecting mTOR. Therefore, we investigated the pharmacologic mechanism of rapamycin treating epilepsy through bioinformatics analysis, cellular experiments and supercomputer simulation. METHODS: Bioinformatics analysis was used to analyze targets of rapamycin treating epilepsy. We established epilepsy cell model by HT22 cells. RT-qPCR, WB and IF were used to verify the effects of rapamycin on mTOR at gene level and protein level. Computer simulations were used to model and evaluate the stability of rapamycin binding to mTOR protein. RESULTS: Bioinformatics indicated mTOR played an essential role in signaling pathways of cell growth and cell metabolism. Cellular experiments showed that rapamycin could promote cell survival, and rapamycin did not have an effect on mRNA expression of mTOR. However, rapamycin was able to significantly inhibit the phosphorylation of mTOR at protein level. Computer simulations indicated that rapamycin was involved in the treatment of epilepsy through regulating phosphorylation of mTOR at protein level. CONCLUSION: We found that rapamycin was capable of promoting the survival of epilepsy cells by inhibiting the phosphorylation of mTOR at protein level, and rapamycin did not have an effect on mRNA expression of mTOR. In addition to the traditional study that rapamycin affects mTORC1 complex by acting on FKBP12, this study found rapamycin could also directly block the phosphorylation of mTOR, therefore affecting the assembly of mTORC1 complex and mTOR signaling pathway.

Modulating plant-soil microcosm with green synthesized ZnONPs in arsenic contaminated soil.

Biogenic nanoparticle (NP), derived from plant sources, is gaining prominence as a viable, cost-effective, sustainable, and biocompatible alternative for mitigating the extensive environmental impact of arsenic on the interplay between plant-soil system. Herein, the impact of green synthesized zinc oxide nanoparticles (ZnONPs) was assessed on Catharanthus roseus root system-associated enzymes and their possible impact on microbiome niches (rhizocompartments) and overall plant performance under arsenic (As) gradients. The application of ZnONPs at different concentrations successfully modified the arsenic uptake in various plant parts, with the root arsenic levels increasing 1.5 and 1.4-fold after 25 and 50 days, respectively, at medium concentration compared to the control. Moreover, ZnONPs gradients regulated the various soil enzyme activities. Notably, urease and catalase activities showed an increase when exposed to low concentrations of ZnONPs, whereas saccharase and acid phosphatase displayed the opposite pattern, showing increased activities under medium concentration which possibly in turn influence the plant root system associated microflora. The use of nonmetric multidimensional scaling ordination revealed a significant differentiation (with a significance level of p < 0.05) in the structure of both bacterial and fungal communities under different treatment conditions across root associated niches. Bacterial and fungal phyla level analysis showed that Proteobacteria and Basidiomycota displayed a significant increase in relative abundance under medium ZnONPs concentration, as opposed to low and high concentrations, respectively. Similarly, in depth genera level analysis revealed that Burkholderia, Halomonas, Thelephora and Sebacina exhibited a notably high relative abundance in both the rhizosphere and rhizoplane (the former refers to the soil region influenced by root exudates, while the latter is the root surface itself) under medium concentrations of ZnONPs, respectively. These adjustments to the plant root-associated microcosm likely play a role in protecting the plant from oxidative stress by regulating the plant's antioxidant system and overall biomass.

Graphene enhances artemisinin production in the traditional medicinal plant Artemisia annua via dynamic physiological processes and miRNA regulation.

We investigated the effects of graphene on the model herb Artemisia annua, which is renowned for producing artemisinin, a widely used pharmacological compound. Seedling growth and biomass were promoted when A. annua was cultivated with low concentrations of graphene, an effect which was attributed to a 1.4-fold increase in nitrogen uptake, a 15%-22% increase in chlorophyll fluorescence, and greater abundance of carbon cycling-related bacteria. Exposure to 10 or 20 mg/L graphene resulted in a âˆ¼60% increase in H2O2, and graphene could act as a catalyst accelerator, leading to a 9-fold increase in catalase (CAT) activity in vitro and thereby maintaining reactive oxygen species (ROS) homeostasis. Importantly, graphene exposure led to an 80% increase in the density of glandular secreting trichomes (GSTs), in which artemisinin is biosynthesized and stored. This contributed to a 5% increase in artemisinin content in mature leaves. Interestingly, expression of miR828 was reduced by both graphene and H2O2 treatments, resulting in induction of its target gene AaMYB17, a positive regulator of GST initiation. Subsequent molecular and genetic assays showed that graphene-induced H2O2 inhibits micro-RNA (miRNA) biogenesis through Dicers and regulates the miR828-AaMYB17 module, thus affecting GST density. Our results suggest that graphene may contribute to yield improvement in A. annua via dynamic physiological processes together with miRNA regulation, and it may thus represent a new cultivation strategy for increasing yield capacity through nanobiotechnology.

Integrating transcriptome and physiological analyses to elucidate the molecular responses of sorghum to fluxofenim and metolachlor herbicide.

The extensive use of herbicides has raised concerns about crop damage, necessitating the development of effective herbicide safeners. Fluxofenim has emerged as a promising herbicide safener; however, it's underlying mechanism remains unclear. Here, we screened two inbred lines 407B and HYZ to investigate the detoxication of fluxofenim in mitigating metolachlor damage in sorghum. Metolachlor inhibited seedling growth in both 407B and HYZ, while, fluxofenim could significantly restore the growth of 407B, but not effectively complement the growth of HYZ. Fluxofenim significantly increased the activities of glutathione-S-transferase (GST) to decrease metolachlor residue in 407B, but not in HYZ. This implys that fluxofenim may reduce metolachlor toxicity by regulating its metabolism. Furthermore, metolachlor suppressed AUX-related and JA-related genes expression, while up-regulated the expression of SA-related genes. Fluxofenim also restored the expression of AUX-related and JA-related genes inhibited by metolachlor and further increased expression of SA-related genes. Moreover, we noted a significant increase in the content of trans-zeatin O-glucoside (tZOG) and Gibberellin1 (GA1) after the fluxofenim treatment. In conclusion, fluxofenim may reduce the injury of herbicide by affecting herbicide metabolism and regulating hormone signaling pathway.

Routes and methods of neural stem cells injection in cerebral ischemia.

Cerebral ischemia is a serious cerebrovascular disease with the characteristics of high morbidity, disability, and mortality. Currently, stem cell therapy has been extensively applied to a wide range of diseases, including neurological disorders, autoimmune deficits, and other diseases. Transplantation therapy with neural stem cells (NSCs) is a very promising treatment method, which not only has anti-inflammatory, antiapoptotic, promoting angiogenesis, and neurogenesis effects, but also can improve some side effects related to thrombolytic therapy. NSCs treatment could exert protective effects in alleviating cerebral ischemia-induced brain damage and neurological dysfunctions. However, the different injection routes and doses of NSCs determine diverse therapeutic efficacy. This review mainly summarizes the various injection methods and injection effects of NSCs in cerebral ischemia, as well as proposes the existing problems and prospects of NSCs transplantation.

Integration of transcriptome and metabolome analyses reveals sorghum roots responding to cadmium stress through regulation of the flavonoid biosynthesis pathway.

Cadmium (Cd) pollution is a serious threat to plant growth and human health. Although the mechanisms controlling the Cd response have been elucidated in other species, they remain unknown in Sorghum (Sorghum bicolor (L.) Moench), an important C4 cereal crop. Here, one-week-old sorghum seedlings were exposed to different concentrations (0, 10, 20, 50, 100, and 150 µM) of CdCl2 and the effects of these different concentrations on morphological responses were evaluated. Cd stress significantly decreased the activities of the enzymes peroxidase (POD), superoxide dismutase (SOD), glutathione S-transferase (GST) and catalase (CAT), and increased malondialdehyde (MDA) levels, leading to inhibition of plant height, decreases in lateral root density and plant biomass production. Based on these results, 10 µM Cd concentration was chosen for further transcription and metabolic analyses. A total of 2683 genes and 160 metabolites were found to have significant differential abundances between the control and Cd-treated groups. Multi-omics integrative analysis revealed that the flavonoid biosynthesis pathway plays a critical role in regulating Cd stress responses in sorghum. These results provide new insights into the mechanism underlying the response of sorghum to Cd.

Molecular docking and molecular dynamics study Lianhua Qingwen granules (LHQW) treats COVID-19 by inhibiting inflammatory response and regulating cell survival.

Purpose: 2019 Coronavirus disease (COVID-19) is endangering health of populations worldwide. Latest research has proved that Lianhua Qingwen granules (LHQW) can reduce tissue damage caused by inflammatory reactions and relieve patients' clinical symptoms. However, the mechanism of LHQW treats COVID-19 is currently lacking. Therefore, we employed computer simulations to investigate the mechanism of LHQW treats COVID-19 by modulating inflammatory response. Methods: We employed bioinformatics to screen active ingredients in LHQW and intersection gene targets. PPI, GO and KEGG was used to analyze relationship of intersection gene targets. Molecular dynamics simulations validated the binding stability of active ingredients and target proteins. Binding free energy, radius of gyration and the solvent accessible surface area were analyzed by supercomputer platform. Results: COVID-19 had 4628 gene targets, LHQW had 1409 gene targets, intersection gene targets were 415. Bioinformatics analysis showed that intersection targets were closely related to inflammation and immunomodulatory. Molecular docking suggested that active ingredients (including: licopyranocoumarin, Glycyrol and 3-3-Oxopropanoic acid) in LHQW played a role in treating COVID-19 by acting on CSF2, CXCL8, CCR5, NLRP3, IFNG and TNF. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets. Conclusion: The mechanism of active ingredients in LHQW treats COVID-19 was investigated by computer simulations. We found that active ingredients in LHQW not only reduce cell damage and tissue destruction by inhibiting the inflammatory response through CSF2, CXCL8, CCR5 and IFNG, but also regulate cell survival and growth through NLRP3 and TNF thereby reducing apoptosis.

Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics.

Purpose: 2019 Coronavirus disease (COVID-19) has caused millions of confirmed cases and deaths worldwide. TMPRSS2-mediated hydrolysis and maturation of spike protein is essential for SARS-CoV-2 infection in vivo. The latest research found that a TMPRSS2 inhibitor called N-0385 could effectively prevent the infection of the SARS-CoV-2 and its variants. However, it is not clear about the mechanism of N-0385 treatment COVID-19. Therefore, this study used computer simulations to investigate the mechanism of N-0385 treatment COVID-19 by impeding SARS-CoV-2 infection. Methods: The GeneCards database was used to search disease gene targets, core targets were analyzed by PPI, GO and KEGG. Molecular docking and molecular dynamics were used to validate and analyze the binding stability of small molecule N-0385 to target proteins. The supercomputer platform was used to simulate and analyze the number of hydrogen bonds, binding free energy, stability of protein targets at the residue level, radius of gyration and solvent accessible surface area. Results: There were 4,600 COVID-19 gene targets from GeneCards database. PPI, GO and KEGG analysis indicated that signaling pathways of immune response and inflammation played crucial roles in COVID-19. Molecular docking showed that N-0385 could block SARS-CoV-2 infection and treat COVID-19 by acting on ACE2, TMPRSS2 and NLRP3. Molecular dynamics was used to demonstrate that the small molecule N-0385 could form very stable bindings with TMPRSS2 and TLR7. Conclusion: The mechanism of N-0385 treatment COVID-19 was investigated by molecular docking and molecular dynamics simulation. We speculated that N-0385 may not only inhibit SARS-CoV-2 invasion directly by acting on TMPRSS2, ACE2 and DPP4, but also inhibit the immune recognition process and inflammatory response by regulating TLR7, NLRP3 and IL-10 to prevent SARS-CoV-2 invasion. Therefore, these results suggested that N-0385 may act through multiple targets to reduce SARS-CoV-2 infection and damage caused by inflammatory responses.

Comparative Genomics and Functional Studies of Putative m6A Methyltransferase (METTL) Genes in Cotton.

N6-methyladenosine (m6A) RNA modification plays important regulatory roles in plant development and adapting to the environment, which requires methyltransferases to achieve the methylation process. However, there has been no research regarding m6A RNA methyltransferases in cotton. Here, a systematic analysis of the m6A methyltransferase (METTL) gene family was performed on twelve cotton species, resulting in six METTLs identified in five allotetraploid cottons, respectively, and three to four METTLs in the seven diploid species. Phylogenetic analysis of protein-coding sequences revealed that METTL genes from cottons, Arabidopsis thaliana, and Homo sapiens could be classified into three clades (METTL3, METTL14, and METTL-like clades). Cis-element analysis predicated the possible functions of METTL genes in G. hirsutum. RNA-seq data revealed that GhMETTL14 (GH_A07G0817/GH_D07G0819) and GhMETTL3 (GH_A12G2586/GH_D12G2605) had high expressions in root, stem, leaf, torus, petal, stamen, pistil, and calycle tissues. GhMETTL14 also had the highest expression in 20 and 25 dpa fiber cells, implying a potential role at the cell wall thickening stage. Suppressing GhMETTL3 and GhMETTL14 by VIGS caused growth arrest and even death in G. hirsutum, along with decreased m6A abundance from the leaf tissues of VIGS plants. Overexpression of GhMETTL3 and GhMETTL14 produced distinct differentially expressed genes (DEGs) in A. thaliana, indicating their possible divergent functions after gene duplication. Overall, GhMETTLs play indispensable but divergent roles during the growth of cotton plants, which provides the basis for the systematic investigation of m6A in subsequent studies to improve the agronomic traits in cotton.

Molecular docking and molecular dynamics simulation study the mechanism of progesterone in the treatment of spinal cord injury.

PURPOSE: Spinal cord injury can lead to incomplete or complete loss of voluntary movement and sensory function, leading to serious complications. Numerous studies have shown that progesterone exhibits strong therapeutic potential for spinal cord injury. However, the mechanism by which progesterone treats spinal cord injury remains unclear. Therefore, this article explores the mechanism of progesterone in the treatment of spinal cord injury by means of molecular docking and molecular dynamics simulation. METHODS: We used bioinformatics to screen active pharmaceutical ingredients and potential targets, and molecular docking and molecular dynamics were used to validate and analysis by the supercomputer platform. RESULTS: Progesterone had 3606 gene targets, spinal cord injury had 6560 gene targets, the intersection gene targets were 2355. GO and KEGG analysis showed that the abundant pathways involved multiple pathways related to cell metabolism and inflammation. Molecular docking showed that progesterone played a role in treating spinal cord injury by acting on BDNF, AR, NGF and TNF. Molecular dynamics was used to prove and analyzed the binding stability of active ingredients and protein targets, and AR/Progesterone combination has the strongest binding energy. CONCLUSION: Progesterone promotes recovery from spinal cord injury by promoting axonal regeneration, remyelination, neuronal survival and reducing inflammation.

Exploring the mechanism of action of dapansutrile in the treatment of gouty arthritis based on molecular docking and molecular dynamics.

Purpose: Dapansutrile is an orally active ß-sulfonyl nitrile compound that selectively inhibits the NLRP3 inflammasome. Clinical studies have shown that dapansutrile is active in vivo and limits the severity of endotoxin-induced inflammation and joint arthritis. However, there is currently a lack of more in-depth research on the effect of dapansutrile on protein targets such as NLRP3 in gouty arthritis. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of dapansutrile on NLRP3 and other related protein targets. Methods: We use bioinformatics to screen active pharmaceutical ingredients and potential disease targets. The disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were utilized to verify and analyze the binding stability of small molecule drugs to target proteins. The supercomputer platform was used to measure and analyze the binding free energy, the number of hydrogen bonds, the stability of the protein target at the residue level, the radius of gyration and the solvent accessible surface area. Results: The protein interaction network screened out the core protein targets (such as: NLRP3, TNF, IL1B) of gouty arthritis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that gouty arthritis mainly played a vital role by the signaling pathways of inflammation and immune response. Molecular docking showed that dapansutrile play a role in treating gouty arthritis by acting on the related protein targets such as NLRP3, IL1B, IL6, etc. Molecular dynamics was used to prove and analyze the binding stability of active ingredients and protein targets, the simulation results found that dapansutrile forms a very stable complex with IL1B. Conclusion: We used bioinformatics analysis and computer simulation system to comprehensively explore the mechanism of dapansutrile acting on NLRP3 and other protein targets in gouty arthritis. This study found that dapansutrile may not only directly inhibit NLRP3 to reduce the inflammatory response and pyroptosis, but also hinder the chemotaxis and activation of inflammatory cells by regulating IL1B, IL6, IL17A, IL18, MMP3, CXCL8, and TNF. Therefore, dapansutrile treats gouty arthritis by attenuating inflammatory response, inflammatory cell chemotaxis and extracellular matrix degradation by acting on multiple targets.

Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation.

Purpose: The rapid worldwide spread of Corona Virus Disease 2019 (COVID-19) has become not only a global challenge, but also a lack of effective clinical treatments. Studies have shown that licorice can significantly improve clinical symptoms such as fever, dry cough and shortness of breath in COVID-19 patients with no significant adverse effects. However, there is still a lack of in-depth analysis of the specific active ingredients of licorice in the treatment of COVID-19 and its mechanism of action. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of action of licorice in the treatment of COVID-19. Methods: We used bioinformatics to screen active pharmaceutical ingredients and potential targets, the disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were carried out to verify that active ingredients were stably combined with protein targets. The supercomputer platform was used to measure and analyze stability of protein targets at the residue level, solvent accessible surface area, number of hydrogen bonds, radius of gyration and binding free energy. Results: Licorice had 255 gene targets, COVID-19 had 4,628 gene targets, the intersection gene targets were 101. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) analysis showed that licorice played an important role mainly through the signaling pathways of inflammatory factors and oxidative stress. Molecular docking showed that Glycyrol, Phaseol and Glyasperin F in licorice may playe a role in treating COVID-19 by acting on STAT3, IL2RA, MMP1, and CXCL8. Molecular dynamics were used to demonstrate and analyze the binding stability of active ingredients to protein targets. Conclusion: This study found that Phaseol in licorice may reduce inflammatory cell activation and inflammatory response by inhibiting the activation of CXCL8 and IL2RA; Glycyrol may regulate cell proliferation and survival by acting on STAT3. Glyasperin F may regulate cell growth by inhibiting the activation of MMP1, thus reducing tissue damage and cell death caused by excessive inflammatory response and promoting the growth of new tissues. Therefore, licorice is proposed as an effective candidate for the treatment of COVID-19 through STAT3, IL2RA, MMP1, and CXCL8.

Exploring the Mechanism of Aspirin in the Treatment of Kawasaki Disease Based on Molecular Docking and Molecular Dynamics.

Purpose: The research aims to investigate the mechanism of action of aspirin in the treatment of Kawasaki disease. Methods: We predicted the targets of aspirin with the help of the Drugbank and PharmMapper databases, the target genes of Kawasaki disease were mined in the GeneCards and Disgenet databases, the intersection targets were processed in the Venny database, and the gene expression differences were observed in the GEO database. The Drugbank and PharmMapper databases were used to predict the target of aspirin, and the target genes of Kawasaki disease were explored in the GeneCards and Disgenet databases, and the Venny was used for intersection processing. We observed the gene expression differences in the GEO database. The disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulation verification was carried out to combine the active ingredient and the target with a stable combination. The supercomputer platform was used to measure and analyze the binding free energy, the number of hydrogen bonds, the stability of the protein target at the residue level, the radius of gyration, and the solvent accessible surface area. Results: Aspirin had 294 gene targets, Kawasaki disease had 416 gene targets, 42 intersecting targets were obtained, we screened 13 core targets by PPI; In the GO analysis, we learned that the biological process of Kawasaki disease involved the positive regulation of chemokine biosynthesis and inflammatory response; pathway enrichment involved PI3K-AKT signaling pathway, tumor necrosis factor signaling pathway, etc. After molecular docking, the data showed that CTSG, ELANE, and FGF1 had the best binding degree to aspirin. Molecular dynamics was used to prove and analyze the binding stability of active ingredients and protein targets, and Aspirin/ELANE combination has the strongest binding energy. Conclusion: In the treatment of Kawasaki disease, aspirin may regulate inflammatory response and vascular remodeling through CTSG, ELANE, and FGF1.

Exploring the mechanism of action of Xuanfei Baidu granule (XFBD) in the treatment of COVID-19 based on molecular docking and molecular dynamics.

Purpose: The Corona Virus Disease 2019 (COVID-19) pandemic has become a challenge of world. The latest research has proved that Xuanfei Baidu granule (XFBD) significantly improved patient's clinical symptoms, the compound drug improves immunity by increasing the number of white blood cells and lymphocytes, and exerts anti-inflammatory effects. However, the analysis of the effective monomer components of XFBD and its mechanism of action in the treatment of COVID-19 is currently lacking. Therefore, this study used computer simulation to study the effective monomer components of XFBD and its therapeutic mechanism. Methods: We screened out the key active ingredients in XFBD through TCMSP database. Besides GeneCards database was used to search disease gene targets and screen intersection gene targets. The intersection gene targets were analyzed by GO and KEGG. The disease-core gene target-drug network was analyzed and molecular docking was used for verification. Molecular dynamics simulation verification was carried out to combine the active ingredient and the target with a stable combination. The supercomputer platform was used to measure and analyze the number of hydrogen bonds, the binding free energy, the stability of protein target at the residue level, the solvent accessible surface area, and the radius of gyration. Results: XFBD had 1308 gene targets, COVID-19 had 4600 gene targets, the intersection gene targets were 548. GO and KEGG analysis showed that XFBD played a vital role by the signaling pathways of immune response and inflammation. Molecular docking showed that I-SPD, Pachypodol and Vestitol in XFBD played a role in treating COVID-19 by acting on NLRP3, CSF2, and relieve the clinical symptoms of SARS-CoV-2 infection. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets, CSF2/I-SPD combination has the strongest binding energy. Conclusion: For the first time, it was found that the important active chemical components in XFBD, such as I-SPD, Pachypodol and Vestitol, reduce inflammatory response and apoptosis by inhibiting the activation of NLRP3, and reduce the production of inflammatory factors and chemotaxis of inflammatory cells by inhibiting the activation of CSF2. Therefore, XFBD can effectively alleviate the clinical symptoms of COVID-19 through NLRP3 and CSF2.