Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic valu...Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic value of PLK3 in glioma remained unexplored.Methods:We analyzed PLK3 expression in glioma samples from multiple databases.Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma,and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression.Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration.The trans-well assay for PLK3 on the immune cells recruitment was also determined.Additionally,we further evaluated the correlation between PLK3 and PD-1/PD-L1 as well as other immune checkpoints.Results:We found that an increased level of PLK3 was associated with malignancy and poor prognosis of glioma,and further validated that PLK3 promoted glioma progression.PLK3 also played a crucial role in immune response and was involved in Tcell immune suppression.Specifically,we revealed that CD8^(+)and CD4^(+)Tcell infiltration was decreased in Plk3 overexpressed xenografts.Furthermore,it was predicted that PLK3 was synergistic with other checkpoint members in glioma.In general,high expression of PLK3 was associated with a malignant process and poor prognosis in glioma patients.Conclusion:Our findings indicated that PLK3 expression level was highly correlated to the malignancy of gliomas,and we validated that PLK3 could promote the GBM progress in vitro and in vivo.Furthermore,PLK3 played important roles in Tcell and neutrophil immune response in glioma.Besides,the conspicuous association between PLK3 and other immune checkpoints was also observed.Crucially,high-level PLK3 expression was revealed to be related to poor clinical prognosis.These results demonstrated that PLK3 may serve as a prognostic biomarker and a potential target for glioma.展开更多
Metastasis is the main cause of cancer-associated mortality. During this complicated process, some cancer cells, also called circulating tumor cells （CTCs）, detach from primary sites, enter bloodstream and extravasa...Metastasis is the main cause of cancer-associated mortality. During this complicated process, some cancer cells, also called circulating tumor cells （CTCs）, detach from primary sites, enter bloodstream and extravasate at metastatic site. Thrombocytosis is frequently observed in patients with metastatic cancers suggesting the important role of platelets in metastasis. Therefore this review focuses on how platelets facilitate the generation of CTCs, protect them from various host attacks, such as immune assaults, apoptosis and shear stress, and regulate CTCs intravasation/extravasation. Platelet-derived cytokines and receptors are involved in this cascade. Identification the mechanisms underlie platelet-CTCs interactions could lead to the development of new platelet-targeted therapeutic strategy to reduce metastasis.展开更多
Histone lysine methylation can be removed by JmjC domain-containing proteins in a sequence- and methylationstate-specific manner. However, how substrate specificity is determined and how the enzymes are regulated were...Histone lysine methylation can be removed by JmjC domain-containing proteins in a sequence- and methylationstate-specific manner. However, how substrate specificity is determined and how the enzymes are regulated were largely unknown. We recently found that ceKDM7A, a PHD- and JmjC domain-containing protein, is a histone demethylase specific for H3K9me2 and H3K27me2, and the PHD finger binding to H3K4me3 guides the demethylation activity in vivo. To provide structural insight into the molecular mechanisms for the enzymatic activity and the function of the PHD finger, we solved six crystal structures of the enzyme in apo form and in complex with single or two peptides containing various combinations of H3K4me3, H3K9me2, and H3K27me2 modifications. The structures indicate that H3Kgme2 and H3K27me2 interact with ceKDMTA in a similar fashion, and that the peptide-binding specificity is determined by a network of specific interactions. The geometrical measurement of the structures also revealed that H3K4me3 associated with the PHD finger and H3K9me2 bound to the JmjC domain are from two separate molecules, suggesting a trans-histone peptide-binding mechanism. Thus, our systemic structural studies reveal not only the substrate recognition by the catalytic domain but also more importantly, the molecular mechanism of dual specifieity of ceDKM7A for both H3K9me2 and H3K27me2.展开更多
As we know more about Zika virus(ZIKV), as well as its linkage to birth defects(microcephaly) and autoimmune neurological syndromes, we realize the importance of developing an efficient vaccine against it. Zika virus ...As we know more about Zika virus(ZIKV), as well as its linkage to birth defects(microcephaly) and autoimmune neurological syndromes, we realize the importance of developing an efficient vaccine against it. Zika virus disease has affected many countries and is becoming a major public health concern. To deal with the infection of ZIKV, plenty of experiments have been done on selection of neutralizing antibodies that can target the envelope(E) protein on the surface of the virion. However, the existence of antibody-dependent enhancement(ADE) effect might limit the use of them as therapeutic candidates. In this review, we classify the neutralizing antibodies against ZIKV based on the epitopes and summarize the resolved structural information on antibody/antigen complex from X-ray crystallography and cryo-electron microscopy(cryo-EM), which might be useful for further development of potent neutralizing antibodies and vaccines toward clinical use.展开更多
Ebola virus(EBOV) belongs to the Filoviridae family and causes severe illnesses such as hemorrhagic fever with a high mortality rate up to 90%. Now two antibody drugs termed Inmazeb and Ebanga have been approved for t...Ebola virus(EBOV) belongs to the Filoviridae family and causes severe illnesses such as hemorrhagic fever with a high mortality rate up to 90%. Now two antibody drugs termed Inmazeb and Ebanga have been approved for treating EBOV infection. However, clinical studies have demonstrated that the mortality rate of the patients who received these two antibody drugs remains above 30%. Therefore, novel therapeutics with better efficacy is still desired. The isolated human IgG1 constant domain 2(CH2 domain) has been proposed as a scaffold for the development of C-based single domain antibodies(C-sd Abs) as therapeutic candidates against viral infections and other diseases. Here, we screened and identified a novel C-sd Ab termed M24 that targets EBOV glycoprotein(GP) from a C-sd Ab phage display library. M24 neutralizes the pseudotype EBOV with IC;of 0.8 nmol/L(12 ng/mL) and has modest neutralizing activity against authentic EBOV.Epitope determination, including molecular docking and site mutation analysis, discloses that M24 binds to the internal fusion loop(IFL) within GP2, a transmembrane subunit of GP. Interestingly, we found that the binding of M24 to GP at pH5.5 has dramatically decreased compared to the binding at pH 7.5, which may lead to weak efficacy in the neutralization of authentic EBOV. Since no sd Ab against EBOV infection has been reported to date, our results not only give a proof of concept that sd Abs could be utilized for the development of potential therapeutic candidates against EBOV infection, but also provide useful information for the discovery and improvement of anti-EBOV agents.展开更多
Dear Editor,For decades,contaminated and misidentified cell lines in biological research remains a serious problem which the researchers call it"identity crisis"(Masters J R,2009).As reported in March 15,201...Dear Editor,For decades,contaminated and misidentified cell lines in biological research remains a serious problem which the researchers call it"identity crisis"(Masters J R,2009).As reported in March 15,2010 by U.S.Food展开更多
More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last dec...More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.展开更多
●AIM:To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty(SLAK)with corneal crosslinking(CXL)on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomi...●AIM:To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty(SLAK)with corneal crosslinking(CXL)on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomileusis(FS-LASIK).●METHODS:A series of 5 patients undertaking SLAK with CXL for the treatment of corneal ectasia secondary to FS-LASIK were followed for 4-9mo.The lenticules were collected from patients undertaking small incision lenticule extraction(SMILE)for the correction of myopia.Adding a stromal lenticule was aimed at improving the corneal thickness for the safe application of crosslinking and compensating for the thin cornea to improve its mechanical strength.●RESULTS:All surgeries were conducted successfully with no significant complications.Their best corrected visual acuity(BCVA)ranged from 0.05 to 0.8-2 before surgery.The pre-operational total corneal thickness ranged from 345-404μm and maximum keratometry(Kmax)ranged from 50.8 to 86.3.After the combination surgery,both the corneal keratometry(range 55.9 to 92.8)and total corneal thickness(range 413-482μm)significantly increased.Four out of 5 patients had improvement of corneal biomechanical parameters(reflected by stiffness parameter A1 in Corvis ST).However,3 patients showed decreased BCVA after surgery due to the development of irregular astigmatism and transient haze.Despite the onset of corneal edema right after SLAK,the corneal topography and thickness generally stabilized after 3mo.●CONCLUSION:SLAK with CXL is a potentially beneficial and safe therapy for advanced corneal ectasia.Future work needs to address the poor predictability of corneal refractometry and compare the outcomes of different surgical modes.展开更多
Nipah virus(NiV)is a zoonotic paramyxovirus in the genus Henipavirus that is prevalent in Southeast Asia.NiV leads to severe respiratory disease and encephalitis in humans and animals,with a mortality rate of up to 75...Nipah virus(NiV)is a zoonotic paramyxovirus in the genus Henipavirus that is prevalent in Southeast Asia.NiV leads to severe respiratory disease and encephalitis in humans and animals,with a mortality rate of up to 75%.Despite the grave threat to public health and global biosecurity,no medical countermeasures are available for humans.Here,based on self-assembled ferritin nanoparticles(FeNPs),we successfully constructed two candidate FeNP vaccines by loading mammalian cells expressing NiV sG(residues 71–602,FeNP-sG)and Ghead(residues 182–602,FeNP-Ghead)onto E.coli-expressed FeNPs(FeNP-sG and FeNP-Ghead,respectively)through Spycatcher/Spytag technology.Compared with sG and Ghead alone,FeNP-sG and FeNP-Ghead elicited significant NiV specific neutralizing antibody levels and T-cell responses in mice,whereas the immune response in the FeNP-sG immunized group was greater than that in the FeNP-Ghead group.These results further demonstrate that sG possesses greater antigenicity than Ghead and that FeNPs can dramatically enhance immunogenicity.Furthermore,FeNP-sG provided 100%protection against NiV challenge in a hamster model when it was administered twice at a dose of 5μg/per animal.Our study provides not only a promising candidate vaccine against NiV,but also a theoretical foundation for the design of a NiV immunogen for the development of novel strategies against NiV infection.展开更多
Objective:To explore the therapeutic target and molecular mechanism of Herba Eupatorii in the intervention of COVID-19(coronavirus disease 2019)by network pharmacology.Methods:TCMSP(Traditional Chinese Medicine System...Objective:To explore the therapeutic target and molecular mechanism of Herba Eupatorii in the intervention of COVID-19(coronavirus disease 2019)by network pharmacology.Methods:TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform)and TCMIP V2.0(Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine)databases were used to search the active ingredients and corresponding drug targets of Herba Eupatorii.Related targets of COVID-19 were searched in Genecards,pharmGKB,CTD,Drugbank and TTD databases.After the intersection targets were selected using VENNY 2.1 online platform,the PPI(protein-protein interaction)network was downloaded into STRING database,and the data were analyzed and sorted out using Cytoscape software to obtain the potential key targets for the treatment of COVID-19 by Herba Eupatorii.At the same time,using the data of active ingredients and intersection targets,a network of"TCM-active ingredients-key targets"was constructed in Cytoscape software to screen out chemical molecules with potential therapeutic effects.GO(Gene Ontology)functional enrichment analysis and KEGG(Kyoto Encyclopedia of Genes)pathway enrichment analysis of key target proteins were performed by R software.AutoDock Vina program was used for molecular docking of the top 5 active ingredients and key targets to calculate the minimum binding energy.Results:There were 26 active ingredients,160 targets,and 1969 pathogenic genes of COVID-19,among which 59 genes were intersection targets of drugs and diseases.After PPI network screening,the key target proteins were AKT1(RAC-alpha serine/threonine-protein kinase),JUN(transcription factor AP-1),TP53(cellular tumor antigen p53),ACTB(actin beta)and EGFR(epidermal growth factor receptor).Through the network of"TCM-Active Ingredients-Key Targets",Luteolin,Eupatolin,Stigmasterol,Eupatoriopicrin and Dammaradienyl acetate were identified as the active ingredients with potential therapeutic effects in the treatment of COVID-19.After R software was used for GO enrichment analysis,1978 GO items were obtained(P<0.05),including 1870 BP items,26 CC items and 82 MF items.149 pathways were obtained by KEGG enrichment analysis(P<0.05).It mainly involves IL-17(interleukin-17)signaling pathway,TNF(tumor necrosis factor)signaling pathway,C-type lectin receptor signaling pathway,PI3K-Akt(phosphatidylinositol 3 kinase-protein kinase B)signaling pathway,and T Cell receptor signaling pathway,etc.The molecular docking results showed that the active ingredients had good binding activity with key targets.Conclusion:Through the potential chemical constituents of Luteolin,Eupatolin,Stigmasterol,Eupatoriopicrin and Dammaradienyl acetate,Herba Eupatorii may act on AKT1,JUN,TP53,ACTB,EGFR and other targets.Involvement in IL-17 signaling pathway,TNF signaling pathway,C-Type Lectin receptor signaling pathway,PI3K-Akt signaling pathway,T Cell receptor signaling pathway and other pathways play an anti-inflammatory and antiviral roles in intervening in the occurrence and development of COVID-19.展开更多
BACKGROUND Due to frequent and high-risk sports activities,the elbow joint is susceptible to injury,especially to cartilage tissue,which can cause pain,limited movement and even loss of joint function.AIM To evaluate ...BACKGROUND Due to frequent and high-risk sports activities,the elbow joint is susceptible to injury,especially to cartilage tissue,which can cause pain,limited movement and even loss of joint function.AIM To evaluate magnetic resonance imaging(MRI)multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury.METHODS A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study.We analyzed the accuracy of conventional MRI sequences(T1-weighted imaging,T2-weighted imaging,proton density weighted imaging,and T2 star weighted image)and Three-Dimensional Coronary Imaging by Spiral Scanning(3D-CISS)in the diagnosis of elbow cartilage injury.Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy.RESULTS The diagnostic accuracy of 3D-CISS sequence was 89.34%±4.98%,the sensitivity was 90%,and the specificity was 88.33%,which showed the best performance among all sequences(P<0.05).The combined application of the whole sequence had the highest accuracy in all sequence combinations,the accuracy of mild injury was 91.30%,the accuracy of moderate injury was 96.15%,and the accuracy of severe injury was 93.33%(P<0.05).Compared with arthroscopy,the combination of all MRI sequences had the highest consistency of 91.67%,and the kappa value reached 0.890(P<0.001).CONCLUSION Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults.Multisequence MRI is recommended to ensure the best diagnosis and treatment.展开更多
Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has posed a continuous threat to global public health.A number of vaccines,such as inactivated vaccines,mRNA vaccines,recombinant ade...Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has posed a continuous threat to global public health.A number of vaccines,such as inactivated vaccines,mRNA vaccines,recombinant adenovirus vector vaccines and protein subunit vaccines,have been licensed and have achieved tremendous success in preventing infections,particularly severe hospitalization and death(Feikin et al.,2022;Ssentongo et al.,2022).However,with the emergence of new variants,breakthrough infections have occurred among vaccines,highlighting the need to develop broad-spectrum vaccines(Ukwishaka et al.,2023).展开更多
Radix Phytolaccae is the dried root of Phytolacca acinosa Roxb or P.ameri-cana L,which is commonly used as a traditional Chinese medicine to treat diseases like cirrhotic ascites,hepatitis B,nephrotic syndrome,psorias...Radix Phytolaccae is the dried root of Phytolacca acinosa Roxb or P.ameri-cana L,which is commonly used as a traditional Chinese medicine to treat diseases like cirrhotic ascites,hepatitis B,nephrotic syndrome,psoriasis,etc.However,there is no exact basis for its clinical application safety.In this paper,the toxic effects and mechanism of Saponin A(EsA),the main component of Radix Phytolaccae,were summarized by searching the results and reports of toxicology related to the plant from 1991 to 2023 on CNKI and pubmed,aiming to provide reference for the toxicological research and future research direction of Radix Phytolaccae,so that Radix Phytolaccae can be safely and effectively used in clinical practice.展开更多
Introduction Rheumatoid arthritis(RA)is a chronic autoimmune disease that results in a series of inflammatory reactions in the joints,marked by pathologies such as articular bone destruction and erosive synovial infla...Introduction Rheumatoid arthritis(RA)is a chronic autoimmune disease that results in a series of inflammatory reactions in the joints,marked by pathologies such as articular bone destruction and erosive synovial inflammatory cartilage[1].The bone destruction in RA arises from an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts[2].The pathogenesis of RA remains unknown,and studies have indicated its close relationship with genetics,the environment,immune response,and other factors.Potential genes linked to RA susceptibility include major histocompatibility complex genes,like the single nucleotide polymorphism rs9277535 in the HLA-DP subunit HLA-DPB1,which is strongly associated with RA susceptibility in the Western Chinese population[3].Furthermore,studies have also identified a correlation between major genes encoding the inflammatory CASPs(CASP1,CASP4,and CASP5)and RA[4].Environmental factors,including smoking,diet,obesity,and infections,have the ability to trigger RA in susceptible individuals[5,6].Regarding the immune response,both immune dysregulation and overactivity can result in an inflammatory response,leading to excessive proliferation of synovial tissue,imbalanced distribution of osteoblasts and osteoclasts,and an irregular proportion of immune cells,culminating in the disease.展开更多
Objective:To explore the potential mechanism of hepatotoxicity induced by Aconitum brachypodum through network toxicology.Methods:The active components and targets of Aconitum brachypodum were identified and screened ...Objective:To explore the potential mechanism of hepatotoxicity induced by Aconitum brachypodum through network toxicology.Methods:The active components and targets of Aconitum brachypodum were identified and screened by CNKI,PubChem database,Swiss Target Prediction database.Genecards,pharmGKB and DisGeNET databases were used to collect hepatotoxicity related targets.The intersection targets were obtained by matching the active component targets with the hepatotoxic targets of Aconitum brachypodum.Cytoscape software was used to construct the"Aconitum brachypodum-potential active components-potential targets-hepatotoxicity"network.The STRING database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted by R software.The toxic components in Aconitum brachypodum were docked with the core targets.Results:In this study,26 chemical components were screened via SwissADME,297 targets for the active components of Aconitum brachypodum were obtained.There were 1,096 hepatotoxicity-related targets,73 potential targets for hepatotoxicity caused by Aconitum brachypodum,and 15 potential active components,among which Penduline,Songoramine,Sitosterol,Daucosterol and Bullatine A were the key active components for hepatotoxicity caused by Aconitum brachypodum,and signal transducer and activator of transcription 3(STAT3),epidermal growth factor receptor(EGFR),mitogen-activated protein kinase 8(MAPK8)and tyrosine-protein kinase JAK2(JAK2)were the potential targets for hepatotoxicity caused by Aconitum brachypodum.There were 1,133 GO entries(P<0.05),including 1,045 entries of biological process(BP),19 entries of cellular component(CC),and 69 entries of molecular function(MF).KEGG enrichment analysis revealed 115 pathways(P<0.05),of which EGFR tyrosine kinase inhibitor resistance,hypoxia-inducible factor 1(HIF-1)signaling pathway,PI3K-Akt signaling pathway,calcium signaling pathway,T helper 17(Th17)cell differentiation was strongly correlated with the hepatotoxicity caused by Aconitum brachypodum.Molecular docking results showed that the binding activity was good.Conclusion:Through network toxicology analysis,it was found that the active ingredients in Aconitum brachypodum may act on multiple targets and signaling pathways,thereby participating in the activation of an excessive inflammatory response,oxidative stress,apoptosis and other pathways on the whole,thus resulting in hepatotoxicity.展开更多
Objective:Based on network pharmacology and molecular docking to explore the mechanism of Wumei Pill in the treatment of non-erosive reflux disease(NERD).Method:We collected the active ingredients and targets of Wumei...Objective:Based on network pharmacology and molecular docking to explore the mechanism of Wumei Pill in the treatment of non-erosive reflux disease(NERD).Method:We collected the active ingredients and targets of Wumei Pill by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and collected NERD related targets through Genecards,PharmGKB,Drugbank,DisGeNET,OMIM,CTD and TTD databases.Intersection targets of Wumei Pill targets and NERD related targets were the potential targets of Wumei Pill in the treatment of NERD.We imported the intersection targets into the STRING database to obtain the PPI network,and obtained the hub targets.The network diagram of"Drugs-Potential active ingredients-Potential targets"was constructed by Cytoscape 3.7.2 software.We used R software to perform Gene Ontology function enrichment analysis(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis(KEGG)on hub targets,and then performed molecular docking verification.Results:There were 129 active ingredients and 213 drug targets of Wumei Pill of which 114 were the intersection targets.1587 GO enrichment items were identified(P<0.05),including 1,491 biological processes,11 cell components,and 85 molecular functions.143 KEGG pathways(P<0.05),mainly related to Kaposi sarcoma-associated herpesvirus infection,IL-17 signaling pathway,the TNF signaling pathway,MAPK signaling pathway.Results of molecular docking showed that the potential active ingredients in Wumei Pill had relatively stable binding activity to the key targets.Conclusion:Wumei pill for the treatment of non-erosive reflux disease are main active ingredients quercetin,kaempferol,beta sitosterol,Isocorypalmine,Stigmasterol,rutaecarpine,etc,the main targets is JUN,TP53,AKT1,may inhibit excessive inflammation,antioxidant therapy effect into full play.This provided a certain theoretical basis for clinical application.展开更多
Objective:To explore the potential mechanism of hepatotoxicity induced by Nux Vomica through network toxicology.Methods:The active components and targets of Nux Vomica were identified and screened by Traditional Chine...Objective:To explore the potential mechanism of hepatotoxicity induced by Nux Vomica through network toxicology.Methods:The active components and targets of Nux Vomica were identified and screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database(TCMSP),literature research,PubChem Database,Swiss Target Prediction database,etc.Genecards,pharmGKB and OMIM databases were used to collect hepatotoxicity related targets,then,cross them with active component targets to obtain potential targets of hepatotoxicity caused by Nux Vomica.A"Nux Vomica-Potential active components-Potential targets-Hepatotoxicity"network was constructed with Cytoscape 3.8.0 software.The String 11.0 database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted by R software,and then the obtained pathways directly related to hepatotoxicity were integrated.Results:In this study,37 active components were screened via TCMSP and literature research,468 targets for the active components of Nux Vomica were obtained.There were 533 hepatotoxicity-related targets,73 potential targets for hepatotoxicity caused by Nux Vomica,and 26 potential active components,among which Ferulic acid,Novacine,Icajine,Simiarenol were the key active components for hepatotoxicity caused by Nux Vomica,and JUN,RELA,and STAT3 were the core target proteins of hepatotoxicity caused by Nux Vomica.There were 1859 GO entries(P-value<0.05),including 1709 entries of Biological Process(BP),39 entries of Cellular Component(CC),and 111 entries of Molecular Function(MF).KEGG enrichment analysis revealed 145 pathways(value<0.05),of which PI3K/AKT signaling pathway,HIF-1 signaling pathway,EGFR tyrosine kinase inhibitor resistance were strongly correlated with the hepatotoxicity caused by Nux Vomica.Conclusion:Through network toxicology analysis,it was found that lots of potential components in Nux Vomica may be involved in the activation of the excessive inflammatory response,oxidative stress,and the LPS response through multiple targets and multiple pathways,resulting in the generation of hepatotoxicity.展开更多
Gout is a metabolic bone and joint disease caused by purine metabolism disorder.The disturbance of inflammatory microenvironment caused by monosodium urate(MSU)deposition is an important pathological mechanism of gout...Gout is a metabolic bone and joint disease caused by purine metabolism disorder.The disturbance of inflammatory microenvironment caused by monosodium urate(MSU)deposition is an important pathological mechanism of gout occurrence and development.In the understanding of Traditional Chinese medicine(TCM),the interaction of"dampness","heat"and"stasis"is the main pathogenesis of gout,and the method of clearing heat and removing dampness is the main treatment method of TCM for gout.In recent years,studies have found that heat-clearing and dampness-removing method can improve the TCM symptom score of gout patients,especially in the body tiredness,dry mouth and dry throat,short yellow urine,thirsty,etc.,which are the characteristics of dampness and heat syndrome,this may be related to the fact that the TCM heat-clearing and dampness-removing method in the treatment of gout removes the appearance of dampness and heat,improves the inflammatory microenvironment of gout and restores the normal metabolic function of human body.This paper deeply explores the specific mechanism of TCM heat-clearing and dampness-removing method to improve the inflammatory microenvironment of gout,which can provide new ideas for the diagnosis and treatment of clinical gout.展开更多
基金supported by the Nature Science Foundation of Chongqing(Nos.cstc2016jcyjA0838 and cstc2020jcyj-msxmX0376).
文摘Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic value of PLK3 in glioma remained unexplored.Methods:We analyzed PLK3 expression in glioma samples from multiple databases.Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma,and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression.Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration.The trans-well assay for PLK3 on the immune cells recruitment was also determined.Additionally,we further evaluated the correlation between PLK3 and PD-1/PD-L1 as well as other immune checkpoints.Results:We found that an increased level of PLK3 was associated with malignancy and poor prognosis of glioma,and further validated that PLK3 promoted glioma progression.PLK3 also played a crucial role in immune response and was involved in Tcell immune suppression.Specifically,we revealed that CD8^(+)and CD4^(+)Tcell infiltration was decreased in Plk3 overexpressed xenografts.Furthermore,it was predicted that PLK3 was synergistic with other checkpoint members in glioma.In general,high expression of PLK3 was associated with a malignant process and poor prognosis in glioma patients.Conclusion:Our findings indicated that PLK3 expression level was highly correlated to the malignancy of gliomas,and we validated that PLK3 could promote the GBM progress in vitro and in vivo.Furthermore,PLK3 played important roles in Tcell and neutrophil immune response in glioma.Besides,the conspicuous association between PLK3 and other immune checkpoints was also observed.Crucially,high-level PLK3 expression was revealed to be related to poor clinical prognosis.These results demonstrated that PLK3 may serve as a prognostic biomarker and a potential target for glioma.
基金supported by grants from the National Natural Science Foundation of China(No. 81300347)the Natural Science Foundation of Jiangxi Province,China(No.20132BAB205037,20151BAB215008, 20151BBG70200)+1 种基金Foundation of Jiangxi Educational Committee(No.GJJ14192)Foundation of Health and Family Planning Commission of Jiangxi Province(No. 20155592,20155103)
文摘Metastasis is the main cause of cancer-associated mortality. During this complicated process, some cancer cells, also called circulating tumor cells （CTCs）, detach from primary sites, enter bloodstream and extravasate at metastatic site. Thrombocytosis is frequently observed in patients with metastatic cancers suggesting the important role of platelets in metastasis. Therefore this review focuses on how platelets facilitate the generation of CTCs, protect them from various host attacks, such as immune assaults, apoptosis and shear stress, and regulate CTCs intravasation/extravasation. Platelet-derived cytokines and receptors are involved in this cascade. Identification the mechanisms underlie platelet-CTCs interactions could lead to the development of new platelet-targeted therapeutic strategy to reduce metastasis.
文摘Histone lysine methylation can be removed by JmjC domain-containing proteins in a sequence- and methylationstate-specific manner. However, how substrate specificity is determined and how the enzymes are regulated were largely unknown. We recently found that ceKDM7A, a PHD- and JmjC domain-containing protein, is a histone demethylase specific for H3K9me2 and H3K27me2, and the PHD finger binding to H3K4me3 guides the demethylation activity in vivo. To provide structural insight into the molecular mechanisms for the enzymatic activity and the function of the PHD finger, we solved six crystal structures of the enzyme in apo form and in complex with single or two peptides containing various combinations of H3K4me3, H3K9me2, and H3K27me2 modifications. The structures indicate that H3Kgme2 and H3K27me2 interact with ceKDMTA in a similar fashion, and that the peptide-binding specificity is determined by a network of specific interactions. The geometrical measurement of the structures also revealed that H3K4me3 associated with the PHD finger and H3K9me2 bound to the JmjC domain are from two separate molecules, suggesting a trans-histone peptide-binding mechanism. Thus, our systemic structural studies reveal not only the substrate recognition by the catalytic domain but also more importantly, the molecular mechanism of dual specifieity of ceDKM7A for both H3K9me2 and H3K27me2.
基金funded by the External Cooperation Program of Chinese Academy of Sciences (Grant No. 153211KYSB20160001)the National Key Research and Development Program of China (Grant No. 2016YFC1202902)+1 种基金the Key Program of Chinese Academy of Sciences (Grant No. ZDRW-ZS2016-4)funded by FNLCR Contract HHSN261200800001E
文摘As we know more about Zika virus(ZIKV), as well as its linkage to birth defects(microcephaly) and autoimmune neurological syndromes, we realize the importance of developing an efficient vaccine against it. Zika virus disease has affected many countries and is becoming a major public health concern. To deal with the infection of ZIKV, plenty of experiments have been done on selection of neutralizing antibodies that can target the envelope(E) protein on the surface of the virion. However, the existence of antibody-dependent enhancement(ADE) effect might limit the use of them as therapeutic candidates. In this review, we classify the neutralizing antibodies against ZIKV based on the epitopes and summarize the resolved structural information on antibody/antigen complex from X-ray crystallography and cryo-electron microscopy(cryo-EM), which might be useful for further development of potent neutralizing antibodies and vaccines toward clinical use.
基金This work was jointly supported by the Advanced Customer Cultivation Project of Wuhan National Biosafety Laboratory,Chinese Academy of Sciences(2021ACCP-MS01,2019ACCP-ZD03)the Natural Science Foundation of Hubei Province of China(2019CFA076)the National Natural Science Foundation of China(31870926)。
文摘Ebola virus(EBOV) belongs to the Filoviridae family and causes severe illnesses such as hemorrhagic fever with a high mortality rate up to 90%. Now two antibody drugs termed Inmazeb and Ebanga have been approved for treating EBOV infection. However, clinical studies have demonstrated that the mortality rate of the patients who received these two antibody drugs remains above 30%. Therefore, novel therapeutics with better efficacy is still desired. The isolated human IgG1 constant domain 2(CH2 domain) has been proposed as a scaffold for the development of C-based single domain antibodies(C-sd Abs) as therapeutic candidates against viral infections and other diseases. Here, we screened and identified a novel C-sd Ab termed M24 that targets EBOV glycoprotein(GP) from a C-sd Ab phage display library. M24 neutralizes the pseudotype EBOV with IC;of 0.8 nmol/L(12 ng/mL) and has modest neutralizing activity against authentic EBOV.Epitope determination, including molecular docking and site mutation analysis, discloses that M24 binds to the internal fusion loop(IFL) within GP2, a transmembrane subunit of GP. Interestingly, we found that the binding of M24 to GP at pH5.5 has dramatically decreased compared to the binding at pH 7.5, which may lead to weak efficacy in the neutralization of authentic EBOV. Since no sd Ab against EBOV infection has been reported to date, our results not only give a proof of concept that sd Abs could be utilized for the development of potential therapeutic candidates against EBOV infection, but also provide useful information for the discovery and improvement of anti-EBOV agents.
基金supported by The Fifth Batch of "China Optics Valley 3551 Talent Program"
文摘Dear Editor,For decades,contaminated and misidentified cell lines in biological research remains a serious problem which the researchers call it"identity crisis"(Masters J R,2009).As reported in March 15,2010 by U.S.Food
基金This project has been funded in whole or in part with federal funds from the National Cancer Institute,National Institutes of Health, under contract N01-CO-12400
文摘More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.
基金Supported by the Science&Technology Department of Sichuan Province(China)Funding Project(No.2021YFS0221,No.2023YFS0179)1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.2022HXFH032,No.ZYJC21058)the Postdoctoral Research Funding of West China Hospital,Sichuan University,China(No.2020HXBH044).
文摘●AIM:To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty(SLAK)with corneal crosslinking(CXL)on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomileusis(FS-LASIK).●METHODS:A series of 5 patients undertaking SLAK with CXL for the treatment of corneal ectasia secondary to FS-LASIK were followed for 4-9mo.The lenticules were collected from patients undertaking small incision lenticule extraction(SMILE)for the correction of myopia.Adding a stromal lenticule was aimed at improving the corneal thickness for the safe application of crosslinking and compensating for the thin cornea to improve its mechanical strength.●RESULTS:All surgeries were conducted successfully with no significant complications.Their best corrected visual acuity(BCVA)ranged from 0.05 to 0.8-2 before surgery.The pre-operational total corneal thickness ranged from 345-404μm and maximum keratometry(Kmax)ranged from 50.8 to 86.3.After the combination surgery,both the corneal keratometry(range 55.9 to 92.8)and total corneal thickness(range 413-482μm)significantly increased.Four out of 5 patients had improvement of corneal biomechanical parameters(reflected by stiffness parameter A1 in Corvis ST).However,3 patients showed decreased BCVA after surgery due to the development of irregular astigmatism and transient haze.Despite the onset of corneal edema right after SLAK,the corneal topography and thickness generally stabilized after 3mo.●CONCLUSION:SLAK with CXL is a potentially beneficial and safe therapy for advanced corneal ectasia.Future work needs to address the poor predictability of corneal refractometry and compare the outcomes of different surgical modes.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB0490000).
文摘Nipah virus(NiV)is a zoonotic paramyxovirus in the genus Henipavirus that is prevalent in Southeast Asia.NiV leads to severe respiratory disease and encephalitis in humans and animals,with a mortality rate of up to 75%.Despite the grave threat to public health and global biosecurity,no medical countermeasures are available for humans.Here,based on self-assembled ferritin nanoparticles(FeNPs),we successfully constructed two candidate FeNP vaccines by loading mammalian cells expressing NiV sG(residues 71–602,FeNP-sG)and Ghead(residues 182–602,FeNP-Ghead)onto E.coli-expressed FeNPs(FeNP-sG and FeNP-Ghead,respectively)through Spycatcher/Spytag technology.Compared with sG and Ghead alone,FeNP-sG and FeNP-Ghead elicited significant NiV specific neutralizing antibody levels and T-cell responses in mice,whereas the immune response in the FeNP-sG immunized group was greater than that in the FeNP-Ghead group.These results further demonstrate that sG possesses greater antigenicity than Ghead and that FeNPs can dramatically enhance immunogenicity.Furthermore,FeNP-sG provided 100%protection against NiV challenge in a hamster model when it was administered twice at a dose of 5μg/per animal.Our study provides not only a promising candidate vaccine against NiV,but also a theoretical foundation for the design of a NiV immunogen for the development of novel strategies against NiV infection.
文摘Objective:To explore the therapeutic target and molecular mechanism of Herba Eupatorii in the intervention of COVID-19(coronavirus disease 2019)by network pharmacology.Methods:TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform)and TCMIP V2.0(Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine)databases were used to search the active ingredients and corresponding drug targets of Herba Eupatorii.Related targets of COVID-19 were searched in Genecards,pharmGKB,CTD,Drugbank and TTD databases.After the intersection targets were selected using VENNY 2.1 online platform,the PPI(protein-protein interaction)network was downloaded into STRING database,and the data were analyzed and sorted out using Cytoscape software to obtain the potential key targets for the treatment of COVID-19 by Herba Eupatorii.At the same time,using the data of active ingredients and intersection targets,a network of"TCM-active ingredients-key targets"was constructed in Cytoscape software to screen out chemical molecules with potential therapeutic effects.GO(Gene Ontology)functional enrichment analysis and KEGG(Kyoto Encyclopedia of Genes)pathway enrichment analysis of key target proteins were performed by R software.AutoDock Vina program was used for molecular docking of the top 5 active ingredients and key targets to calculate the minimum binding energy.Results:There were 26 active ingredients,160 targets,and 1969 pathogenic genes of COVID-19,among which 59 genes were intersection targets of drugs and diseases.After PPI network screening,the key target proteins were AKT1(RAC-alpha serine/threonine-protein kinase),JUN(transcription factor AP-1),TP53(cellular tumor antigen p53),ACTB(actin beta)and EGFR(epidermal growth factor receptor).Through the network of"TCM-Active Ingredients-Key Targets",Luteolin,Eupatolin,Stigmasterol,Eupatoriopicrin and Dammaradienyl acetate were identified as the active ingredients with potential therapeutic effects in the treatment of COVID-19.After R software was used for GO enrichment analysis,1978 GO items were obtained(P<0.05),including 1870 BP items,26 CC items and 82 MF items.149 pathways were obtained by KEGG enrichment analysis(P<0.05).It mainly involves IL-17(interleukin-17)signaling pathway,TNF(tumor necrosis factor)signaling pathway,C-type lectin receptor signaling pathway,PI3K-Akt(phosphatidylinositol 3 kinase-protein kinase B)signaling pathway,and T Cell receptor signaling pathway,etc.The molecular docking results showed that the active ingredients had good binding activity with key targets.Conclusion:Through the potential chemical constituents of Luteolin,Eupatolin,Stigmasterol,Eupatoriopicrin and Dammaradienyl acetate,Herba Eupatorii may act on AKT1,JUN,TP53,ACTB,EGFR and other targets.Involvement in IL-17 signaling pathway,TNF signaling pathway,C-Type Lectin receptor signaling pathway,PI3K-Akt signaling pathway,T Cell receptor signaling pathway and other pathways play an anti-inflammatory and antiviral roles in intervening in the occurrence and development of COVID-19.
文摘BACKGROUND Due to frequent and high-risk sports activities,the elbow joint is susceptible to injury,especially to cartilage tissue,which can cause pain,limited movement and even loss of joint function.AIM To evaluate magnetic resonance imaging(MRI)multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury.METHODS A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study.We analyzed the accuracy of conventional MRI sequences(T1-weighted imaging,T2-weighted imaging,proton density weighted imaging,and T2 star weighted image)and Three-Dimensional Coronary Imaging by Spiral Scanning(3D-CISS)in the diagnosis of elbow cartilage injury.Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy.RESULTS The diagnostic accuracy of 3D-CISS sequence was 89.34%±4.98%,the sensitivity was 90%,and the specificity was 88.33%,which showed the best performance among all sequences(P<0.05).The combined application of the whole sequence had the highest accuracy in all sequence combinations,the accuracy of mild injury was 91.30%,the accuracy of moderate injury was 96.15%,and the accuracy of severe injury was 93.33%(P<0.05).Compared with arthroscopy,the combination of all MRI sequences had the highest consistency of 91.67%,and the kappa value reached 0.890(P<0.001).CONCLUSION Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults.Multisequence MRI is recommended to ensure the best diagnosis and treatment.
文摘Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has posed a continuous threat to global public health.A number of vaccines,such as inactivated vaccines,mRNA vaccines,recombinant adenovirus vector vaccines and protein subunit vaccines,have been licensed and have achieved tremendous success in preventing infections,particularly severe hospitalization and death(Feikin et al.,2022;Ssentongo et al.,2022).However,with the emergence of new variants,breakthrough infections have occurred among vaccines,highlighting the need to develop broad-spectrum vaccines(Ukwishaka et al.,2023).
文摘Radix Phytolaccae is the dried root of Phytolacca acinosa Roxb or P.ameri-cana L,which is commonly used as a traditional Chinese medicine to treat diseases like cirrhotic ascites,hepatitis B,nephrotic syndrome,psoriasis,etc.However,there is no exact basis for its clinical application safety.In this paper,the toxic effects and mechanism of Saponin A(EsA),the main component of Radix Phytolaccae,were summarized by searching the results and reports of toxicology related to the plant from 1991 to 2023 on CNKI and pubmed,aiming to provide reference for the toxicological research and future research direction of Radix Phytolaccae,so that Radix Phytolaccae can be safely and effectively used in clinical practice.
文摘Introduction Rheumatoid arthritis(RA)is a chronic autoimmune disease that results in a series of inflammatory reactions in the joints,marked by pathologies such as articular bone destruction and erosive synovial inflammatory cartilage[1].The bone destruction in RA arises from an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts[2].The pathogenesis of RA remains unknown,and studies have indicated its close relationship with genetics,the environment,immune response,and other factors.Potential genes linked to RA susceptibility include major histocompatibility complex genes,like the single nucleotide polymorphism rs9277535 in the HLA-DP subunit HLA-DPB1,which is strongly associated with RA susceptibility in the Western Chinese population[3].Furthermore,studies have also identified a correlation between major genes encoding the inflammatory CASPs(CASP1,CASP4,and CASP5)and RA[4].Environmental factors,including smoking,diet,obesity,and infections,have the ability to trigger RA in susceptible individuals[5,6].Regarding the immune response,both immune dysregulation and overactivity can result in an inflammatory response,leading to excessive proliferation of synovial tissue,imbalanced distribution of osteoblasts and osteoclasts,and an irregular proportion of immune cells,culminating in the disease.
文摘Objective:To explore the potential mechanism of hepatotoxicity induced by Aconitum brachypodum through network toxicology.Methods:The active components and targets of Aconitum brachypodum were identified and screened by CNKI,PubChem database,Swiss Target Prediction database.Genecards,pharmGKB and DisGeNET databases were used to collect hepatotoxicity related targets.The intersection targets were obtained by matching the active component targets with the hepatotoxic targets of Aconitum brachypodum.Cytoscape software was used to construct the"Aconitum brachypodum-potential active components-potential targets-hepatotoxicity"network.The STRING database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted by R software.The toxic components in Aconitum brachypodum were docked with the core targets.Results:In this study,26 chemical components were screened via SwissADME,297 targets for the active components of Aconitum brachypodum were obtained.There were 1,096 hepatotoxicity-related targets,73 potential targets for hepatotoxicity caused by Aconitum brachypodum,and 15 potential active components,among which Penduline,Songoramine,Sitosterol,Daucosterol and Bullatine A were the key active components for hepatotoxicity caused by Aconitum brachypodum,and signal transducer and activator of transcription 3(STAT3),epidermal growth factor receptor(EGFR),mitogen-activated protein kinase 8(MAPK8)and tyrosine-protein kinase JAK2(JAK2)were the potential targets for hepatotoxicity caused by Aconitum brachypodum.There were 1,133 GO entries(P<0.05),including 1,045 entries of biological process(BP),19 entries of cellular component(CC),and 69 entries of molecular function(MF).KEGG enrichment analysis revealed 115 pathways(P<0.05),of which EGFR tyrosine kinase inhibitor resistance,hypoxia-inducible factor 1(HIF-1)signaling pathway,PI3K-Akt signaling pathway,calcium signaling pathway,T helper 17(Th17)cell differentiation was strongly correlated with the hepatotoxicity caused by Aconitum brachypodum.Molecular docking results showed that the binding activity was good.Conclusion:Through network toxicology analysis,it was found that the active ingredients in Aconitum brachypodum may act on multiple targets and signaling pathways,thereby participating in the activation of an excessive inflammatory response,oxidative stress,apoptosis and other pathways on the whole,thus resulting in hepatotoxicity.
文摘Objective:Based on network pharmacology and molecular docking to explore the mechanism of Wumei Pill in the treatment of non-erosive reflux disease(NERD).Method:We collected the active ingredients and targets of Wumei Pill by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and collected NERD related targets through Genecards,PharmGKB,Drugbank,DisGeNET,OMIM,CTD and TTD databases.Intersection targets of Wumei Pill targets and NERD related targets were the potential targets of Wumei Pill in the treatment of NERD.We imported the intersection targets into the STRING database to obtain the PPI network,and obtained the hub targets.The network diagram of"Drugs-Potential active ingredients-Potential targets"was constructed by Cytoscape 3.7.2 software.We used R software to perform Gene Ontology function enrichment analysis(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis(KEGG)on hub targets,and then performed molecular docking verification.Results:There were 129 active ingredients and 213 drug targets of Wumei Pill of which 114 were the intersection targets.1587 GO enrichment items were identified(P<0.05),including 1,491 biological processes,11 cell components,and 85 molecular functions.143 KEGG pathways(P<0.05),mainly related to Kaposi sarcoma-associated herpesvirus infection,IL-17 signaling pathway,the TNF signaling pathway,MAPK signaling pathway.Results of molecular docking showed that the potential active ingredients in Wumei Pill had relatively stable binding activity to the key targets.Conclusion:Wumei pill for the treatment of non-erosive reflux disease are main active ingredients quercetin,kaempferol,beta sitosterol,Isocorypalmine,Stigmasterol,rutaecarpine,etc,the main targets is JUN,TP53,AKT1,may inhibit excessive inflammation,antioxidant therapy effect into full play.This provided a certain theoretical basis for clinical application.
文摘Objective:To explore the potential mechanism of hepatotoxicity induced by Nux Vomica through network toxicology.Methods:The active components and targets of Nux Vomica were identified and screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database(TCMSP),literature research,PubChem Database,Swiss Target Prediction database,etc.Genecards,pharmGKB and OMIM databases were used to collect hepatotoxicity related targets,then,cross them with active component targets to obtain potential targets of hepatotoxicity caused by Nux Vomica.A"Nux Vomica-Potential active components-Potential targets-Hepatotoxicity"network was constructed with Cytoscape 3.8.0 software.The String 11.0 database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted by R software,and then the obtained pathways directly related to hepatotoxicity were integrated.Results:In this study,37 active components were screened via TCMSP and literature research,468 targets for the active components of Nux Vomica were obtained.There were 533 hepatotoxicity-related targets,73 potential targets for hepatotoxicity caused by Nux Vomica,and 26 potential active components,among which Ferulic acid,Novacine,Icajine,Simiarenol were the key active components for hepatotoxicity caused by Nux Vomica,and JUN,RELA,and STAT3 were the core target proteins of hepatotoxicity caused by Nux Vomica.There were 1859 GO entries(P-value<0.05),including 1709 entries of Biological Process(BP),39 entries of Cellular Component(CC),and 111 entries of Molecular Function(MF).KEGG enrichment analysis revealed 145 pathways(value<0.05),of which PI3K/AKT signaling pathway,HIF-1 signaling pathway,EGFR tyrosine kinase inhibitor resistance were strongly correlated with the hepatotoxicity caused by Nux Vomica.Conclusion:Through network toxicology analysis,it was found that lots of potential components in Nux Vomica may be involved in the activation of the excessive inflammatory response,oxidative stress,and the LPS response through multiple targets and multiple pathways,resulting in the generation of hepatotoxicity.
文摘Gout is a metabolic bone and joint disease caused by purine metabolism disorder.The disturbance of inflammatory microenvironment caused by monosodium urate(MSU)deposition is an important pathological mechanism of gout occurrence and development.In the understanding of Traditional Chinese medicine(TCM),the interaction of"dampness","heat"and"stasis"is the main pathogenesis of gout,and the method of clearing heat and removing dampness is the main treatment method of TCM for gout.In recent years,studies have found that heat-clearing and dampness-removing method can improve the TCM symptom score of gout patients,especially in the body tiredness,dry mouth and dry throat,short yellow urine,thirsty,etc.,which are the characteristics of dampness and heat syndrome,this may be related to the fact that the TCM heat-clearing and dampness-removing method in the treatment of gout removes the appearance of dampness and heat,improves the inflammatory microenvironment of gout and restores the normal metabolic function of human body.This paper deeply explores the specific mechanism of TCM heat-clearing and dampness-removing method to improve the inflammatory microenvironment of gout,which can provide new ideas for the diagnosis and treatment of clinical gout.
