BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the crit...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.展开更多
Objective:To explore the key targets and mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacological methods.Methods:The effective components and corresp...Objective:To explore the key targets and mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacological methods.Methods:The effective components and corresponding target proteins of Shengjiang Xiexin Decoction were screened by TCMSP,and the target of chemotherapy-induced diarrhea were screened by the GeneCards.R software was used to obtain the common targets of drugs and diseases,and the“component-target-disease”network diagram was constructed by Cytoscape3.8.0 software.The string datebase was used to draw the protein interaction(PPI)network,and the Bioconductor software was used to perform GO function and KEGG pathway enrichment analysis on effective targets.Result:The result showed that 216 components were screened and 276 effective targets were screened.There were 1764 chemotherapy-induced diarrhea targets.The 173 common targets were obtained through venn diagram.The GO function analysis found 2427 items of biological process,168 items of molecular function and 79 items of cellular component.The KEGG pathway analysis found 169 items.Conclusion:The PPI network found that STAT3、AKT1、MAPK3、JUN、MAPK1、RELA、IL6、etc.may be the key targets for Shengjiang Xiexin Decoction in treatment of chemotherapy-induced diarrhea.GO biological processes include DNA-binding transcription factor activity,cytokine receptor binding,cytokine activity,response to lipopolysaccharide,cellular response to chemical stress and so on.The KEGG pathways involved mainly include Toll-like receptor signaling pathway,TNF signaling pathway,inlfuenza A signaling pathway、hepatitise B signaling pathway and other pathways,that Play the role of anti-inflammatory and repair barrier.展开更多
Ti_(3)AlC_(2)samples are irradiated in advance by 3.5 MeV Fe-ion to the fluence of 1.0×10^(16)ion/cm^(2),and then are implanted by 500 keV He-ion with the fluence of 1.0×10^(17)ion/cm^(2)at room temperature....Ti_(3)AlC_(2)samples are irradiated in advance by 3.5 MeV Fe-ion to the fluence of 1.0×10^(16)ion/cm^(2),and then are implanted by 500 keV He-ion with the fluence of 1.0×10^(17)ion/cm^(2)at room temperature.The irradiated samples are investigated by grazing incidence x-ray diffraction(GIXRD)and transmission electron microscopy(TEM).GIXRD results show serious structural distortion,but without amorphization in the irradiated samples.Fe-ion irradiation and He-ion implantation create much more serious structural distortion than single Fe-ion irradiation.TEM results reveal that there are a large number of defect clusters in the damage region,and dense spherical He bubbles appear in the He depositional region.It seems that the pre-damage does not influence the growth of He bubbles,but He-ion implantation influences the pre-created defect configurations.展开更多
基金Supported by National Natural Foundation of China,No.821742232019 Chinese and Western Medicine Clinical Collaborative Capacity Building Project for Major Difficult Diseases,No.2019-ZX-005。
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.
基金National Natural Science Foundation of China(No.81904001)Special Fund for Capital Health Development(No.2018-1-4061)+1 种基金National Administration of Traditional Chinese Medicine of China(No.2019-ZX-005)Hospital Project of China-Japan Friendship Hospital(No.2019-1-QN-56)。
文摘Objective:To explore the key targets and mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacological methods.Methods:The effective components and corresponding target proteins of Shengjiang Xiexin Decoction were screened by TCMSP,and the target of chemotherapy-induced diarrhea were screened by the GeneCards.R software was used to obtain the common targets of drugs and diseases,and the“component-target-disease”network diagram was constructed by Cytoscape3.8.0 software.The string datebase was used to draw the protein interaction(PPI)network,and the Bioconductor software was used to perform GO function and KEGG pathway enrichment analysis on effective targets.Result:The result showed that 216 components were screened and 276 effective targets were screened.There were 1764 chemotherapy-induced diarrhea targets.The 173 common targets were obtained through venn diagram.The GO function analysis found 2427 items of biological process,168 items of molecular function and 79 items of cellular component.The KEGG pathway analysis found 169 items.Conclusion:The PPI network found that STAT3、AKT1、MAPK3、JUN、MAPK1、RELA、IL6、etc.may be the key targets for Shengjiang Xiexin Decoction in treatment of chemotherapy-induced diarrhea.GO biological processes include DNA-binding transcription factor activity,cytokine receptor binding,cytokine activity,response to lipopolysaccharide,cellular response to chemical stress and so on.The KEGG pathways involved mainly include Toll-like receptor signaling pathway,TNF signaling pathway,inlfuenza A signaling pathway、hepatitise B signaling pathway and other pathways,that Play the role of anti-inflammatory and repair barrier.
基金Supported by the National Natural Science Foundation of China under Grant Nos 11405231 and 91426301
文摘Ti_(3)AlC_(2)samples are irradiated in advance by 3.5 MeV Fe-ion to the fluence of 1.0×10^(16)ion/cm^(2),and then are implanted by 500 keV He-ion with the fluence of 1.0×10^(17)ion/cm^(2)at room temperature.The irradiated samples are investigated by grazing incidence x-ray diffraction(GIXRD)and transmission electron microscopy(TEM).GIXRD results show serious structural distortion,but without amorphization in the irradiated samples.Fe-ion irradiation and He-ion implantation create much more serious structural distortion than single Fe-ion irradiation.TEM results reveal that there are a large number of defect clusters in the damage region,and dense spherical He bubbles appear in the He depositional region.It seems that the pre-damage does not influence the growth of He bubbles,but He-ion implantation influences the pre-created defect configurations.
