Background:Based on previous theoretical studies,JQ-1 as a common inhibitor of bromodomain and extraterminal(BET)proteins was used to treat a variety of diseases.Therefore,we aimed to explore the mechanism of action o...Background:Based on previous theoretical studies,JQ-1 as a common inhibitor of bromodomain and extraterminal(BET)proteins was used to treat a variety of diseases.Therefore,we aimed to explore the mechanism of action of JQ-1 on BET proteins based on bioinformatics and build the novel hypothesis of JQ-1 in treating atherosclerosis(AS)caused by proliferation of vascular smooth muscle cells(VSMCs).Methods:We selected the chip GSE138323 which was searched with the key words“Vascular smooth muscle cell proliferation”in Gene Expression Omnibus(GEO)database,and differential gene analysis was performed between the GRO and JQ-1 groups.Then the top twenty significantly up-regulated genes and the top twenty significantly down-regulated genes were selected for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Thirdly,structured the PPI network of forty differential genes,and the core genes were screened by using the MCC algorithm which in“Cytohubba”plugin in the Cytoscapev3.9.1 software.After that,single gene Gene Set Enrichment Analysis(GSEA)enrichment analysis was performed on the selected core genes in R language.Finally molecular docking validation was performed.Results:Five core genes was selected:H3C2,H3C4,H3C7,H3C10 and AREG.The GO enrichment analysis results showed that there were twenty-five entries in biological process,eight entries in cellular components(CC),and twenty-five entries in molecular function.The KEGG enrichment analysis results showed that there were seven pathways,mainly including systemic lupus erythematosus and external neutrophil trap formation.The GSEA results showed that the five genes were mainly through the regulation of cytochrome P450 metabolism,PPAR signaling pathway and other pathways.The molecular docking results showed that JQ-1 had binding activity with these five genes.Conclusions:JQ-1 may regulate the expression of the genes that H3C2,H3C4,H3C7,H3C10 and AREG,to mainly regulate the genes in cytochrome P450 metabolism,PPAR singling pathway and other pathways,to make some influence in the proliferation of VSMCs,and improved atherosclerotic symptoms due to vascular smooth muscle proliferation,thus treating cardiovascular disease.展开更多
以OP-10(辛基酚聚氧乙烯醚)为非离子型表面活性剂、聚乙烯醇(PVA)为基体树脂和列克纳胶(JQ-1)为交联剂,制备了新型单组分交联反应型白色PVA乳胶,并采用正交试验法探讨了乳胶的各组分掺量、反应温度和时间等对剪切强度、产品外观的影响...以OP-10(辛基酚聚氧乙烯醚)为非离子型表面活性剂、聚乙烯醇(PVA)为基体树脂和列克纳胶(JQ-1)为交联剂,制备了新型单组分交联反应型白色PVA乳胶,并采用正交试验法探讨了乳胶的各组分掺量、反应温度和时间等对剪切强度、产品外观的影响。研究结果表明:当PVA为10 g/100 m L、φ(OP-10)=0.03%、φ(JQ-1)=2.5%(均相对于乳胶总体积而言)、反应时间为105 min和反应温度为40℃时,该PVA乳胶的粘接性能和耐水性优良;该PVA乳胶生产工艺简单、原料成本低,可广泛应用于建筑装饰、木材加工、纸品和纺织等行业中。展开更多
Photothermal therapy has been intensively investigated for treating cancer in recent years.However,the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence.To add...Photothermal therapy has been intensively investigated for treating cancer in recent years.However,the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence.To address this challenge,immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites.Here,we engineered silica-based core-shell nanoparticles(JQ-1@PSNs-R),in which silica cores were coated with the photothermal agent polydopamine,and a bromodomain-containing protein 4(BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photo thermal and immune therapy for tumor elimination.Importantly,to improve the therapeutic effect,we increased the surface roughness of the nanoparticles by hydrofluoric acid(HF) etching during the fabrication process,and found that the internalization of JQ-1@PSNs-R was significantly improved,leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1.In the animal studies,the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy,successfully activated tumor-specific immune responses against residual tumor cells,and further prevented tumor metastasis and recurrence.Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.展开更多
基金supported by a grant from Key Project of Education Commission of Hubei Province(D20202802)Hubei Key Laboratory of Diabetes and Angiopathy Program(2020XZ10)of Hubei University of Science.
文摘Background:Based on previous theoretical studies,JQ-1 as a common inhibitor of bromodomain and extraterminal(BET)proteins was used to treat a variety of diseases.Therefore,we aimed to explore the mechanism of action of JQ-1 on BET proteins based on bioinformatics and build the novel hypothesis of JQ-1 in treating atherosclerosis(AS)caused by proliferation of vascular smooth muscle cells(VSMCs).Methods:We selected the chip GSE138323 which was searched with the key words“Vascular smooth muscle cell proliferation”in Gene Expression Omnibus(GEO)database,and differential gene analysis was performed between the GRO and JQ-1 groups.Then the top twenty significantly up-regulated genes and the top twenty significantly down-regulated genes were selected for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Thirdly,structured the PPI network of forty differential genes,and the core genes were screened by using the MCC algorithm which in“Cytohubba”plugin in the Cytoscapev3.9.1 software.After that,single gene Gene Set Enrichment Analysis(GSEA)enrichment analysis was performed on the selected core genes in R language.Finally molecular docking validation was performed.Results:Five core genes was selected:H3C2,H3C4,H3C7,H3C10 and AREG.The GO enrichment analysis results showed that there were twenty-five entries in biological process,eight entries in cellular components(CC),and twenty-five entries in molecular function.The KEGG enrichment analysis results showed that there were seven pathways,mainly including systemic lupus erythematosus and external neutrophil trap formation.The GSEA results showed that the five genes were mainly through the regulation of cytochrome P450 metabolism,PPAR signaling pathway and other pathways.The molecular docking results showed that JQ-1 had binding activity with these five genes.Conclusions:JQ-1 may regulate the expression of the genes that H3C2,H3C4,H3C7,H3C10 and AREG,to mainly regulate the genes in cytochrome P450 metabolism,PPAR singling pathway and other pathways,to make some influence in the proliferation of VSMCs,and improved atherosclerotic symptoms due to vascular smooth muscle proliferation,thus treating cardiovascular disease.
文摘以OP-10(辛基酚聚氧乙烯醚)为非离子型表面活性剂、聚乙烯醇(PVA)为基体树脂和列克纳胶(JQ-1)为交联剂,制备了新型单组分交联反应型白色PVA乳胶,并采用正交试验法探讨了乳胶的各组分掺量、反应温度和时间等对剪切强度、产品外观的影响。研究结果表明:当PVA为10 g/100 m L、φ(OP-10)=0.03%、φ(JQ-1)=2.5%(均相对于乳胶总体积而言)、反应时间为105 min和反应温度为40℃时,该PVA乳胶的粘接性能和耐水性优良;该PVA乳胶生产工艺简单、原料成本低,可广泛应用于建筑装饰、木材加工、纸品和纺织等行业中。
基金the financial support of the National Natural Science Foundation of China (Nos.81925036 & 81872814)the Science & Technology Major Project of Sichuan Province (No.2018SZDZX0018,China)+2 种基金the Key Research and Development Program of Science and Technology Department of Sichuan Province (No.2020YFS0570,China)111 project (No.b18035,China)the Fundamental Research Funds for the Central Universities (China)。
文摘Photothermal therapy has been intensively investigated for treating cancer in recent years.However,the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence.To address this challenge,immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites.Here,we engineered silica-based core-shell nanoparticles(JQ-1@PSNs-R),in which silica cores were coated with the photothermal agent polydopamine,and a bromodomain-containing protein 4(BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photo thermal and immune therapy for tumor elimination.Importantly,to improve the therapeutic effect,we increased the surface roughness of the nanoparticles by hydrofluoric acid(HF) etching during the fabrication process,and found that the internalization of JQ-1@PSNs-R was significantly improved,leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1.In the animal studies,the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy,successfully activated tumor-specific immune responses against residual tumor cells,and further prevented tumor metastasis and recurrence.Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.
