Biology subjects

Liu, M.

Publications and source records attributed to Liu, M..

At least 451 records · Page 25Linked to original sources

bioRxiv2020

A large accessory genome, high recombination rates, and selection of secondary metabolite genes help maintain global distribution and broad host range of the fungal plant pathogen Claviceps purpurea

Pangenome analyses are increasingly being utilized to study the evolution of eukaryotic organisms, which is often governed by variable gene content. While pangenomes can provide insight into polymorphic gene content, inferences about the ecological and adaptive potential of such organisms also need to be accompanied by additional supportive genomic analyses. In this study we constructed a pangenome of Claviceps purpurea from 24 genomes and examined the positive selection and recombination landscape of an economically important fungal organism for pharmacology and agricultural research. Together, these analyses revealed that C. purpurea has a relatively large accessory genome ([~] 38%) that is likely maintained by high recombination rates ({rho} = 0.044) and transposon mediated gene duplication. However, due to observations of relatively low transposable element (TE) content (8.8%) and a lack of variability in genome sizes, prolific TE expansion is likely controlled by these high recombination rates, which may additionally be influencing the overall trend of purifying selection across the genome. Despite this trend, we observed a strong positive selection pressure on secondary metabolite genes, particularly within the ergoline biosynthetic cluster where we also revealed that the lpsA1 and lpsA2 genes were the result of a recombination event. These results indicate that secondary metabolites are primary factors affecting the diversification of the species into new ecological niches and help maintain its global distribution and broad host range. These results showcase the use of selection and recombination landscapes to identify mechanisms contributing to pangenome structure and primary factors influencing the evolution of an organism. Author SummaryThe use of genomic data to better understand the lifestyle of a pathogen and its relationship with its host has expanded our ability to investigate the evolutionary history of these organisms. This in turn has allowed us to decipher and understand the ambiguity surrounding the true nature of the fungal plant pathogen Claviceps purpurea. By combining three different types of broad genomic analyses we identified primary factors affecting the evolution and adaptive potential of this pathogen; particularly a large accessory genome, high recombination rates, and positive selection of genes associated with stress tolerance. These factors likely contribute to the pathogens global distribution and broad host range. Furthermore, these findings will influence the direction of future research into optimal control methods.

evolutionary biology↗

bioRxiv2020

Tracing two causative SNPs reveals SARS-CoV-2 transmission in North America population

During the COVID-19 pandemic, precisely tracing the route of the SARS-CoV-2 transmission in human population remains challenging. Because this RNA virus can mutate massively without a specifically tracing maker. Herein, using a geographic stratified genome-wide association study (GWAS) of 2599 full-genome sequences, we identified that two SNPs (i.e., 1059.C>T and 25563.G>T) of linkage disequilibrium were presented in approximately half of North America SARS-CoV-2 population (p = 2.44 x 10-212 and p = 2.98 x 10-261), resulting two missense mutations (i.e., Thr 265 Ile and Gln 57 His) in ORF1ab and ORF3a, respectively. Interestingly, these two SNPs exclusively occurred in the North America dominated clade 1, accumulated during mid to late March, 2020. We did not find any of these two SNPs by retrospectively tracing the two SNPs in bat and pangolin related SARS-CoV-2 and human SARS-CoV-2 from the first epicenter Wuhan or other regions of China mainland. This suggested that the SARS-CoV-2 population of Chinese mainland were different from the prevalent strains of North America. Time-dependently, we found that these two SNPs first occurred in Europe SARS-CoV-2 (26-Feb-2020) which was 3 days early than the occurring date of North America isolates and 17 days early for Asia isolates (Taiwan China dominated). Collectively, this population genetic analysis highlights a well-confidential transmission route of the North America isolates and the two SNPs we newly identified are possibly novel diagnosable or druggable targets for surveillance and treatment.

microbiology↗

bioRxiv2020

Antagonistic Effects of Intraspecific Cooperation and Interspecific Competition on Thermal Performance

Understanding how climate-mediated biotic interactions shape thermal niche width is critical in an era of global change. Yet, most previous work on thermal niches has ignored detailed mechanistic information about the relationship between temperature and organismal performance, which can be described by a thermal performance curve. Here, we develop a model that predicts the width of thermal performance curves will be narrower in the presence of interspecific competitors, causing a species optimal breeding temperature to diverge from that of a competitor. We test this prediction in the Asian burying beetle Nicrophorus nepalensis, confirming that the divergence in actual and optimal breeding temperatures is the result of competition with blowflies. However, we further show that intraspecific cooperation enables beetles to outcompete blowflies by recovering their optimal breeding temperature. Ultimately, linking direct (abiotic factors) and indirect effects (biotic interactions) on niche width will be critical for understanding species-specific responses to climate change.

ecology↗

bioRxiv2020

Conformational Selection in Ligand Recognition by the First Tudor Domain of PHF20L1

The first Tudor domain of PHF20L1 (PHF20L1 Tudor1) recognizes both histone methylation and non-histone methylation to play versatile roles, e.g., PHF20L1 Tudor1 binds to the oncogenic target DNA (cytosine-5) methyltransferase 1 (DNMT1) to prevent it from degradation. However, the crystal structure of the PHF20 Tudor domain, a homolog of PHF20L1, reveals a closed aromatic cage of the Tudor domain. It is thus highly desirable to interrogate the ligand-recognition mechanism of PHF20L1 Tudor1, which will in turn validate the potential druggability of this target. Here, we solved the crystal structure of the free form PHF20L1 Tudor1, which adopts the closed conformation similar to PHF20. NMR relaxation dispersion and molecular dynamics (MD) simulations suggest a pre-existing low-population conformation with a remarkable rearrangement of aromatic cage residues. Such structural rearrangement is further revealed by the crystal structures of PHF20L1 Tudor1 in complex with the lysine 142 methylated (K142me1) DNMT1, and a small molecule cosolvent 2-(N-morpholino)ethanesulfonic acid (MES), respectively. This result thus ignites interest in the discovery of small molecule inhibitors against PHF20L1 Tudor1. The hit identified from NMR fragment-based screening protrudes into the same open form aromatic cage of PHF20L1 Tudor1, and blocks the interaction between PHF20L1 Tudor1 and methylated DNMT1. Further free form crystal structures of key mutants reveal one open form and one closed form aromatic cage, which is energetically trapped observed in the NMR relaxation dispersion and MD simulations. The binding of DNMT1 with PHF20L1 Tudor1 mutants was also recapitulated in cancer cells. The mutagenesis thus alters the structure, dynamics and eventually the function of PHF20L1 Tudor1. Our results demonstrate that PHF20L1 Tudor1 utilizes the same conformational selection mechanism to recognize ligands, regardless of whether it is a natural substrate or a small molecule identified from fragment-based screening. Albeit at a low population, the pre-existing ligand-binding conformation shall shift the paradigm in the druggability assessment of a dynamic protein, even though it may lack a small molecule binding pocket in its free form structure. The inhibition of PHF20L1 paves an alternative way to target DNMT1 degradation.

biochemistry↗

bioRxiv2020

Identification of molecular specificity between reprogrammed cardiomyocytes and normal cardiomyocytes by bioinformatics

The adult human heart lacks an effective endogenous repair mechanism and cannot fully restore heart function after injury. We obtained two microarray data sets GSE99814 and GSE22292 from the NCBI GEO database, which include 5 groups of directly reprogrammed cardiomyocyte-like cells (iCMs) and 5 groups of normal mouse cardiomyocytes (CM). And through the GEO2R tool and Venn diagram software to screen the differentially expressed genes (DEG) between iCM and CM. Next, we performed functional enrichment analysis on these DEGs. The protein-protein interaction network (PPI) was constructed by STRING and Cytoscape for module analysis. We have selected a total of 243 DEGs consistently expressed genes in the two data sets, of which 127 up-regulated genes function and pathway enrichment mainly concentrated on biological processes such as innate immune response, inflammatory response, immune system process, positive regulation of apoptosis process and complement and coagulation cascade, while the 116 down-regulated genes are mainly enriched in cell cycle, cell division, cardiac development, myocardial contraction and myocardial cell development and signaling pathways such as cell cycle and adrenergic signaling in cardiomyocytes. Then in the PPI network, we found 27 central genes when analyzing these 243 DEGs by the Molecular Complex Detection (MCODE) plug-in. Finally, we reanalyzed these 27 central genes through DAVID and found that 6 genes (CCNB1, CCNB2, BUB1, TTK, CDC25C, CCNA2) significantly enriched the cell cycle signaling pathway (p <1.20E-07). Therefore, through integrated bioinformatics methods, we found that compary with iCMs and CMs, iCMs were induced by direct reprogramming of neonatal mouse cardiomyocytes, the DEGs were mainly enriched in immune-related processes and myocardial contraction and cell cycle signaling pathways (p < 0.05).

bioinformatics↗

bioRxiv2020

Genus-wide comparison reveals divergence and evolution of the four sections within the genus Claviceps are the result of varying mechanisms driving genome evolution and host range

The genus Claviceps has been known for centuries as an economically important fungal genera for pharmacology and agricultural research. Only recently have researchers begun to unravel the evolutionary history of the genus, with origins in South America and classification of four distinct sections through ecological, morphological, and metabolic features (Claviceps sects. Citrinae, Paspalorum, Pusillae, and Claviceps). The first three sections are additionally characterized by narrow host range, while sect. Claviceps is considered evolutionarily more successful and adaptable as it has the largest host range and biogeographical distribution. However, the reasons for this success and adaptability remain unclear. Our study elucidates factors influencing adaptability by sequencing and annotating 50 Claviceps genomes, representing 21 species, for a comprehensive comparison of genome architecture and plasticity in relation to host range potential. Our results show the trajectory from specialized one-speed genomes (sects. Citrinae and Paspalorum) towards adaptive two-speed genomes (sects. Pusillae and Claviceps) through co-localization of transposable elements around predicted effectors and a putative loss of repeat-induced point mutation resulting in unconstrained tandem gene duplication coinciding with increased host range potential and speciation. Alterations of genomic architecture and plasticity can substantially influence and shape the evolutionary trajectory of fungal pathogens and their adaptability. Furthermore, our study provides a large increase in available genomic resources to propel future studies of Claviceps in pharmacology and agricultural research, as well as, research into deeper understanding of the evolution of adaptable plant pathogens.

evolutionary biology↗

bioRxiv2020

Pattern-recognition receptors are required for NLR-mediated plant immunity

The plant immune system is fundamental to plant survival in natural ecosystems and productivity in crop fields. Substantial evidence supports the prevailing notion that plants possess a two-tiered innate immune system, called pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). PTI is triggered by microbial patterns via cell surface-localized pattern-recognition receptors (PRRs), whereas ETI is activated by pathogen effector proteins via mostly intracellularly-localized receptors called nucleotide-binding, leucine-rich repeat proteins (NLRs)1-4. PTI and ETI are initiated by dist 30 inct activation mechanisms and are considered to act independently and have evolved sequentially5,6. Here we show that, contrary to the perception of PTI and ETI being separate immune signaling pathways, Arabidopsis PRR/co-receptor mutants, fls2/efr/cerk1 and bak1/bkk1/cerk1 triple mutants, are greatly impaired in ETI responses when challenged with incompatible Pseudomonas syrinage bacteria. We further show that the NADPH oxidase (RBOHD)-mediated production of reactive oxygen species (ROS) is a critical early signaling event connecting PRR and NLR cascades and that PRR-mediated phosphorylation of RBOHD is necessary for full activation of RBOHD during ETI. Furthermore, NLR signaling rapidly augments the transcript and protein levels of key PTI components at an early stage and in a salicylic acid-independent manner. Our study supports an alternative model in which PTI is in fact an indispensable component of ETI during bacterial infection, implying that ETI halts pathogen infection, in part, by directly co-opting the anti-pathogen mechanisms proposed for PTI. This alternative model conceptually unites two major immune signaling pathways in the plant kingdom and mechanistically explains the long-observed similarities in downstream defense outputs between PTI and ETI.

plant biology↗

bioRxiv2020

Molecular architecture of the luminal ring of the Xenopus laevis nuclear pore complex

Nuclear pore complex (NPC) mediates the flow of substances between the nucleus and cytoplasm in eukaryotic cells. Here we report the cryo-electron tomography (cryo-ET) structure of the luminal ring (LR) of the NPC from Xenopus laevis oocyte. The observed key structural features of the LR are independently confirmed by single-particle cryo-electron microscopy (cryo-EM) analysis. The LR comprises eight butterfly-shaped subunits, each containing two symmetric wings. Each wing consists of four elongated, tubular protomers. Within the LR subunit, the eight protomers form a Finger domain, which directly contacts the fusion between the inner and outer nuclear membranes, and a Grid domain, which serves as a rigid base for the Finger domain. Two neighbouring LR subunits interact with each other through the lateral edges of their wings to constitute a Bumper domain, which displays two major conformations and appears to cushion neighbouring NPCs. Our study reveals previously unknown features of the LR and potentially explains the elastic property of the NPC.

biophysics↗

bioRxiv2020

Structure of the Cytoplasmic Ring of the Xenopus laevis Nuclear Pore Complex

Nuclear pore complex (NPC) exhibits structural plasticity and has only been characterized at local resolutions of up to 15 [A] for the cytoplasmic ring (CR). Here we present a single-particle cryo-electron microscopy (cryo-EM) structure of the CR from Xenopus laevis NPC at average resolutions of 5.5-7.9 [A], with local resolutions reaching 4.5 [A]. Improved resolutions allow identification and placement of secondary structural elements in the majority of the CR components. The two Y complexes in each CR subunit interact with each other and associate with those from flanking subunits, forming a circular scaffold. Within each CR subunit, the Nup358-containing region wraps around the stems of both Y complexes, likely stabilizing the scaffold. Nup205 connects the short arms of the two Y complexes and associates with the stem of a neighbouring Y complex. The Nup214-containing region uses an extended coiled-coil to link Nup85 of the two Y complexes and protrudes into the axial pore of the NPC. These previously uncharacterized structural features reveal insights into NPC assembly.

biophysics↗

bioRxiv2020

Analysis of genetic signatures of tumor microenvironment yields insight into mechanisms of resistance to immunotherapy

BackgroundTherapeutic intervention targeting immune cells have led to remarkable improvements in clinical outcomes of tumor patients. However, responses are not universal. The inflamed tumor microenvironment has been reported to correlate with response in tumor patients. However, due to the lack of appropriate experimental methods, the reason why the immunotherapeutic resistance still existed on the inflamed tumor microenvironment remains unclear. Materials and methodsHere, based on integrated single-cell RNA sequencing technology, we classified tumor microenvironment into inflamed immunotherapeutic responsive and inflamed non-responsive. Then, phenotype-specific genes were identified to show mechanistic differences between distant TME phenotypes. Finally, we screened for some potential favorable TME phenotypes transformation drugs to aid current immunotherapy. ResultsMultiple signaling pathways were phenotypes-specific dysregulated. For example, Interleukin signaling pathways including IL-4 and IL-13 were activated in inflamed TME across multiple tumor types. PPAR signaling pathways and multiple epigenetic pathways were respectively inhibited and activated in inflamed immunotherapeutic non-responsive TME, suggesting a potential mechanism of immunotherapeutic resistance and target for therapy. We also identified some genetic markers of inflamed non-responsive or responsive TME, some of which have shown its potentials to enhance the efficacy of current immunotherapy. ConclusionThese results may contribute to the mechanistic understanding of immunotherapeutic resistance and guide rational therapeutic combinations of distant targeted chemotherapy agents with immunotherapy.

immunology↗

bioRxiv2020

Pan-cancer analysis identified inflamed microenvironment associated multi-omics signatures

BackgroundImmunotherapy has revolutionized cancer therapy. However, responses are not universal. The inflamed tumor microenvironment has been reported to correlate with response in tumor patients. However, how different tumors shape their tumor microenvironment remains a critical unsolved problem. A deeper insight into the molecular characteristics of inflamed tumor microenvironment may be needed. Materials and methodsHere, based on single-cell RNA sequencing technology and TCGA pan-cancer cohort, we investigated multi-omics molecular features of tumor microenvironment phenotypes. Based on single-cell RNA-seq analysis, we classified pan-cancer tumor samples into inflamed or non-inflamed tumor and identified molecular features of these tumors. Analysis of integrating identified gene signatures with a drug-genomic perturbation database identified multiple drugs which may be helpful for converting non-inflamed tumors to inflamed tumors. ResultsOur results revealed several inflamed/non-inflamed tumor microenvironments-specific molecular characteristics. For example, inflamed tumors highly expressed miR-650 and lncRNA including MIR155HG and LINC00426, these tumors showed activated cytokines-related signaling pathways. Interestingly, non-inflamed tumors tended to express several genes related to neurogenesis. Multi-omics analysis demonstrated the neuro phenotype transformation may be induced by hypomethylated promoters of these genes and down-regulated miR-650. Drug discovery analysis revealed histone deacetylase inhibitors may be a potential choice for helping favorable tumor microenvironment phenotype transformation and aiding current immunotherapy. ConclusionOur results provide a comprehensive molecular-level understanding of tumor cell-immune cell interaction and may have profound clinical implications.

immunology↗

bioRxiv2020

IRF8 Governs Tumor-Associated Macrophage Control of T Cell Exhaustion

Tumor progression is associated with overstimulation of cytotoxic T lymphocytes (CTLs), resulting in a dysfunctional state of exhaustion. How T cell exhaustion is elicited in the tumor remains poorly understood. Here we show that tumor-associated macrophages (TAMs) present cancer cell antigen and induce CTL exhaustion through a gene expression program dependent on the transcription factor interferon regulatory factor-8 (IRF8). In a transgenic model of murine breast cancer, CTL priming was supported by IRF8-dependent dendritic cells; yet, CTL exhaustion required TAM expression of IRF8, and its ablation suppressed tumor growth. An analysis of the highly immune-infiltrated human renal cell carcinoma tumors revealed abundant TAMs that expressed IRF8 and were enriched for an IRF8 gene expression signature. The IRF8 signature co-segregated with T cell exhaustion markers and was negatively associated with long-term patient survival. Thus, CTL exhaustion is promoted by TAMs via IRF8, and this crosstalk may be disrupted in TAM-targeted therapies.

immunology↗

bioRxiv2020

Rhesus macaques can be effectively infected with SARS-CoV-2 via ocular conjunctival route

The outbreak of Corona Virus Disease 2019 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is highly transmitted. The potential extra-respiratory transmission routes remain uncertain. Five rhesus macaques were inoculated with 1x106 TCID50 of SARS-CoV-2 via conjunctival (CJ), intratracheal (IT), and intragastric (IG) routes, respectively. Remarkably, the CJ inoculated-macaques developed mild interstitial pneumonia and viral load was detectable in the conjunctival swabs at 1 days post-inoculation (dpi). Only via IT inoculation, viral load was detected in the anal swab at 1-7 dpi and macaque showed weight loss. However, viral load was undetectable after IG inoculation. Comparatively, viral load was higher in the nasolacrimal system but lesions of lung were relatively mild and local via CJ inoculation compared with that via IT inoculation, demonstrating distinct characteristics of virus dispersion. Both the two routes affected the alimentary tract. Therefore the clinicians need to protect eye while working with patients.

microbiology↗

bioRxiv2020

Reinfection could not occur in SARS-CoV-2 infected rhesus macaques

A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection. One Sentence SummaryNeutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.

microbiology↗

bioRxiv2020

Inhibition of SARS-CoV-2 infection (previously 2019-nCoV) by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion

The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be confirmed. Therefore, we herein used a SARS-CoV-2 spike (S) protein-mediated cell-cell fusion assay and found that SARS-CoV-2 showed plasma membrane fusion capacity superior to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. We then generated a series of lipopeptides and found that the EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than that of EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, potently inhibiting replication of 4 live human coronaviruses, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by currently circulating SARS-CoV-2 and emerging SARSr-CoVs.

microbiology↗

bioRxiv2020

OGP: A Repository of Experimentally Characterized O-Glycoproteins to Facilitate Studies on O-Glycosylation

Numerous studies on cancer, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation. However, the lack of updated and convenient databases deters the storage and utilization of emerging O-glycoprotein data. To resolve this issue, an O-glycoprotein repository named OGP was established in this work. It was constructed with a collection of O-glycoprotein data from different sources. OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far. Based on the recorded O-glycosites, an O-glycosylation site prediction tool was developed. Moreover, an OGP-backed website is already available (http://www.oglyp.org/). The website comprises four specially designed and user-friendly modules: Statistic Analysis, Database Search, Site Prediction, and Data Submit. The first version of OGP repository and the website allow users to obtain vast O-glycoprotein related information, such as protein accession numbers, glycopeptides, site-specific glycan structures, experimental methods, and potential glycosylation sites. O-glycosylation data mining can be performed efficiently on this website, which can greatly facilitates O-glycosylation studies.

bioinformatics↗

bioRxiv2020

TGFβ Suppresses Type 2 Immunity to Cancer

The immune system employs two distinct defense strategies against infections: pathogen elimination typified by type 1 immunity, and pathogen containment exemplified by type 2 immunity in association with tissue repair. Akin to infectious diseases, cancer progresses with cancer cell acquisition of microorganism-like behavior propagating at the expense of the host. While immunological mechanisms of cancer cell elimination are well defined, whether immune-mediated cancer cell containment can be induced is poorly understood. Here we show that ablation of transforming growth factor-{beta} receptor II (TGF{beta}RII) in CD4+ T cells promotes tumor tissue healing and halts cancer progression. Notably, the restorative response is dependent on the T helper 2 cytokine IL-4 fortifying vasculature organization that spares only proximal layers of cancer cells from hypoxia, nutrient starvation and death. Thus, type 2 immunity represents an effective cancer defense mechanism, and TGF{beta} signaling in helper T cells may be targeted for novel cancer immunotherapy.

immunology↗

bioRxiv2020

Exploring the Pharmacological Mechanism of Bezoar on Cerebral Ischemic Stroke using a Network Pharmacology Approach

BackgroundIschemic stroke is a common clinical disease limited by its time window for treatment. In addition to its high mortality rate, only one treatment currently exists for ischemic stroke. Nonetheless, traditional Chinese medicine is often used as a reatment for the disease. Bezoar is a multi-functional drug that has been demonstrated to be effective for the treatment of ischemic stroke. However, its mechanism of action is yet to be fully elucidated. Based on network pharmacology, we explored the potential mechanism of action of bezoar. Symmap and literature data mining methods were used to obtain the target of bezoar. The mechanism of bezoar for the treatment of ischemic stroke was identified and ischemic stroke-related targets were retrieved using DrugBank, Online Mendelian Inheritance in Man, and Therapeutic Target Database. Protein-protein interaction networks were constructed using the Cytoscape plugin, BisoGenet, and analysed by topological methods. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment were carried out via the Database for Annotation, Visualization, and Integrated Discovery server. We obtained 48 potential targets and 3 signalling pathways, including mitogen-activated protein kinase, hypoxia-inducible factor-1, and tumour necrosis factor signalling pathways. The mechanism of action of bezoar on ischemic stroke involves multiple targets and signalling pathways. Our research provides a network pharmacology framework for future Chinese medicinal research.

neuroscience↗