Objective To observe the different expression of NF-kBp65 and cyclinD1 during oral carcinogenesis and to analyze the relationship between the abnormal expression of NF-kBp65 , cyclinD1, and the occurrence and developm...Objective To observe the different expression of NF-kBp65 and cyclinD1 during oral carcinogenesis and to analyze the relationship between the abnormal expression of NF-kBp65 , cyclinD1, and the occurrence and development of oral carcinogenesis. Methods The streptavidin-biotin-peroxidase （S-P） immunohistochemical method was employed to detect the expression of NF-kBp65 and cyclinD1 protein in 38 rat tongue carcinogenesis specimens induced by 4-nitroquinoline 1-oxide. Results With the progress of tongue carcinogenesis, the expression of NF-kBp65, cyclinD1 was up-regulated. In normal, mild epithelial dysplasia, moderate epithelial dysplasia, severe epithelial dysplasia, carcinoma in situ and squamous cell carcinoma （SCC）, the positive rate of NF-kBp65 was 20%, 20%, 50%, 62.5%, 50% and 83.33%, respectively. There was significant differences between normal and SCC （ P 〈 0. 05 ） ; while the level of cyclinD1 was 20%, 60%, 62. 5%, 87. 5% , 100% and 83. 33%, respec- tively. There was significant differences between normal and severe epithelial dysplasia, carcinoma in situ and SCC （ P 〈0.01 or P 〈 0. 05 ）. There was a significant correlation between the increased levels of NF-kBp65, cyclinD1 and histopathological grade. The positive expression of NF-kBp65 was also associated with cyclinD1 in SCC （ r = 0. 7353, P 〈 0. 05 ）. Conclusion The up-expression of NF-kBp65 and cyclinD1 protein may be correlated to the occurrence and the development of oral carcinoma ; activated NF-kB plays an important role in the overexpression of cyclinD1. Furthermore, NF-kB and cyclinD1 may be the useful biomarker of oral precancerous lesion.展开更多
Phenylurea reacted with dichlorophenylphosphine and aldehydes or ketones by Mannich-type reaction in anhydrous benzene to give five-mem- bered phosphorous heterocyclic compounds.However.derivatives of α-ureidoalkylph...Phenylurea reacted with dichlorophenylphosphine and aldehydes or ketones by Mannich-type reaction in anhydrous benzene to give five-mem- bered phosphorous heterocyclic compounds.However.derivatives of α-ureidoalkylphosphonic acids were obtained as the reaction performed in glacial acetic acid.展开更多
Ten 4-substituted bicyclic phosphates were synthesized and their ^(13)C-NMR were also determined.A good relationship was observed between 4-^(13)C chemical shift and Taft σ_X induc- tive paramenters.Substituent effec...Ten 4-substituted bicyclic phosphates were synthesized and their ^(13)C-NMR were also determined.A good relationship was observed between 4-^(13)C chemical shift and Taft σ_X induc- tive paramenters.Substituent effects on ~3J_(P-C) coupling constant were studied.展开更多
Three new metal-organic complexes, namely [Zn(POA)2(H2O)2](1), [Zn(POA)2(H2O)2]·2H2O(2) and [Zn(POA)2]n(3), have been synthesized by organic ligand 2-carboxylic acid-4-nitropyridine-1-oxide(POA) and zinc(Ⅱ) ions...Three new metal-organic complexes, namely [Zn(POA)2(H2O)2](1), [Zn(POA)2(H2O)2]·2H2O(2) and [Zn(POA)2]n(3), have been synthesized by organic ligand 2-carboxylic acid-4-nitropyridine-1-oxide(POA) and zinc(Ⅱ) ions. The structures of complexes 1~3 are characterized by single-crystal X-ray analysis, XRD powder diffraction analysis, infrared spectroscopy and thermal stability analysis method. Complex 1 belongs to monoclinic system, space group C2/c with a = 22.8215(15), b = 7.5613(16), c = 10.048(3) ?, β = 109.47°, V = 1634.7(6) ?~3, Z = 4, F(000) = 944, Dc = 1.900 g/cm^3, C(12)H(10)N4O(12)Zn, Mr = 467.61 and μ = 1.584 mm^(-1). The whole molecule presents "V" shape. Complex 2 is a centrosymmetric structure in triclinic system with space group P1: a = 7.4728(5), b = 7.6825(6), c = 8.5184(6) ?, α = 65.975(2), β = 79.87(2), γ = 89.855(2)°, V = 4384.1(5) ?~3, Z = 1, F(000) = 256, Dc = 1.908 g/cm^3, C(12)H(14)N4O(14)Zn, Mr = 503.64 and μ = 1.492 mm^(-1). Complex 3 is a one-dimensional chain structure belonging to monoclinic system and space group P21/c with a = 4.9456(6), b = 12.5322(14), c = 11.2514(13) ?, β = 97.313(11)°, V = 6916.8(14) ?~3, Z = 2, F(000) = 432, Dc = 2.072 g/cm^3, C(12)H6N4O(10)Zn, Mr = 431.58, and μ = 1.852 mm^(-1). In three complexes, six oxygen atoms from the surrounding coordination atoms form a ZnO6 distorted octahedral coordination geometry around the zinc ions. Meanwhile, fluorescent properties of the three complexes were investigated at room temperature. The fluorescence spectroscopic analysis demonstrated that the ligand POA shows red-shift after coordinating with the zinc(Ⅱ) ions.展开更多
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:This investigation delineates the anti-cancer potency of epigallocatechin-3-gallate(EGCG)in an oral cancer mouse model,with a focus on its effect on T-cell activation.Methods:An oral cancer model was establi...Objective:This investigation delineates the anti-cancer potency of epigallocatechin-3-gallate(EGCG)in an oral cancer mouse model,with a focus on its effect on T-cell activation.Methods:An oral cancer model was established in male Balb/c mice using 4-nitroquinoline 1-oxide(4-NQO).The mice were systematically grouped and administered graded concentrations of EGCG.Key parameters such as body weight,hydration levels,tumor volume,and mass were meticulously tracked.T-cell activity and cytokine expression profiles,focusing on interleukin-2(IL-2),interferon-gamma(IFN-γ),and tumor necrosis factor-alpha(TNF-α),were quantified using ELISA.A comprehensive statistical evaluation included one-way ANOVA,Tukey’s HSD multiple comparison test,and the Kruskal-Wallis non-parametric assessment.Results:EGCG-administered cohorts exhibited a pronounced reduction in tumor size and mass,with the high-dose group showing the greatest efficacy.ELISA findings corroborated a significant increase in T-cell activity and concomitant upregulation of key cytokines,including IL-2,IFN-γ,and TNF-α(P<0.05).Conclusion:This investigation confirms the tumor-suppressive efficacy of EGCG in a murine oral squamous cell carcinoma model.The therapeutic effects of EGCG are mediated through T-cell activation and the upregulation of pivotal cytokine expression,highlighting its potential immunomodulatory role in oral cancer treatment.展开更多
The gut microbiota plays an essential role in intestinal homeostasis. Recent studies indicated that dysbiosis of the gut microbiome may contribute to the development of many disorders, including colon cancer. However,...The gut microbiota plays an essential role in intestinal homeostasis. Recent studies indicated that dysbiosis of the gut microbiome may contribute to the development of many disorders, including colon cancer. However, little is known about the profile of microbial populations during upper gastrointestinal carcinogenesis. In this study, a chemical mutagen, 4-nitroquinoline-1-oxide (4NQO), was used to induce oral and esophageal carcinoma in eight-week old male C57BL/6 mice through their drinking water. The changes in the gut microbiota during oral and esophageal carcinogenesis were investigated through 16S sequencing of DNA extracted from fecal samples. Histological analyses of tissue sections demonstrated various stages of lesions in the tongue and esophagus of mice after 4NQO treatment. There was no significant difference in the diversity of gut microbiota between the 4NQO group and the control group. However, the bacterial composition of gut microbiota was significantly different in the 4NQO group compared with the control group. In conclusion, the current murine model suggests that the gut microbiota may be involved in the occurrence of chemically-induced squamous cell carcinoma in the tongue and esophagus. A better understanding of the definite relationship between the microbiome and upper gastrointestinal carcinogenesis might provide potential targets for the prevention and treatment of related diseases.展开更多
基金Supported by Shanghai Science and Technology Commission,China (03JC14037)
文摘Objective To observe the different expression of NF-kBp65 and cyclinD1 during oral carcinogenesis and to analyze the relationship between the abnormal expression of NF-kBp65 , cyclinD1, and the occurrence and development of oral carcinogenesis. Methods The streptavidin-biotin-peroxidase （S-P） immunohistochemical method was employed to detect the expression of NF-kBp65 and cyclinD1 protein in 38 rat tongue carcinogenesis specimens induced by 4-nitroquinoline 1-oxide. Results With the progress of tongue carcinogenesis, the expression of NF-kBp65, cyclinD1 was up-regulated. In normal, mild epithelial dysplasia, moderate epithelial dysplasia, severe epithelial dysplasia, carcinoma in situ and squamous cell carcinoma （SCC）, the positive rate of NF-kBp65 was 20%, 20%, 50%, 62.5%, 50% and 83.33%, respectively. There was significant differences between normal and SCC （ P 〈 0. 05 ） ; while the level of cyclinD1 was 20%, 60%, 62. 5%, 87. 5% , 100% and 83. 33%, respec- tively. There was significant differences between normal and severe epithelial dysplasia, carcinoma in situ and SCC （ P 〈0.01 or P 〈 0. 05 ）. There was a significant correlation between the increased levels of NF-kBp65, cyclinD1 and histopathological grade. The positive expression of NF-kBp65 was also associated with cyclinD1 in SCC （ r = 0. 7353, P 〈 0. 05 ）. Conclusion The up-expression of NF-kBp65 and cyclinD1 protein may be correlated to the occurrence and the development of oral carcinoma ; activated NF-kB plays an important role in the overexpression of cyclinD1. Furthermore, NF-kB and cyclinD1 may be the useful biomarker of oral precancerous lesion.
基金the National Natural Science Foundation of People's Republic of China:
文摘Phenylurea reacted with dichlorophenylphosphine and aldehydes or ketones by Mannich-type reaction in anhydrous benzene to give five-mem- bered phosphorous heterocyclic compounds.However.derivatives of α-ureidoalkylphosphonic acids were obtained as the reaction performed in glacial acetic acid.
基金Project Supported by National Sciences Foundation of China.
文摘Ten 4-substituted bicyclic phosphates were synthesized and their ^(13)C-NMR were also determined.A good relationship was observed between 4-^(13)C chemical shift and Taft σ_X induc- tive paramenters.Substituent effects on ~3J_(P-C) coupling constant were studied.
基金supported by Industrial pilot(key)project in Fujian Province(No.2017H0018)Subsidized Project for Postgraduates’Innovative Fund in Scientific Research of Huaqiao University。
文摘Three new metal-organic complexes, namely [Zn(POA)2(H2O)2](1), [Zn(POA)2(H2O)2]·2H2O(2) and [Zn(POA)2]n(3), have been synthesized by organic ligand 2-carboxylic acid-4-nitropyridine-1-oxide(POA) and zinc(Ⅱ) ions. The structures of complexes 1~3 are characterized by single-crystal X-ray analysis, XRD powder diffraction analysis, infrared spectroscopy and thermal stability analysis method. Complex 1 belongs to monoclinic system, space group C2/c with a = 22.8215(15), b = 7.5613(16), c = 10.048(3) ?, β = 109.47°, V = 1634.7(6) ?~3, Z = 4, F(000) = 944, Dc = 1.900 g/cm^3, C(12)H(10)N4O(12)Zn, Mr = 467.61 and μ = 1.584 mm^(-1). The whole molecule presents "V" shape. Complex 2 is a centrosymmetric structure in triclinic system with space group P1: a = 7.4728(5), b = 7.6825(6), c = 8.5184(6) ?, α = 65.975(2), β = 79.87(2), γ = 89.855(2)°, V = 4384.1(5) ?~3, Z = 1, F(000) = 256, Dc = 1.908 g/cm^3, C(12)H(14)N4O(14)Zn, Mr = 503.64 and μ = 1.492 mm^(-1). Complex 3 is a one-dimensional chain structure belonging to monoclinic system and space group P21/c with a = 4.9456(6), b = 12.5322(14), c = 11.2514(13) ?, β = 97.313(11)°, V = 6916.8(14) ?~3, Z = 2, F(000) = 432, Dc = 2.072 g/cm^3, C(12)H6N4O(10)Zn, Mr = 431.58, and μ = 1.852 mm^(-1). In three complexes, six oxygen atoms from the surrounding coordination atoms form a ZnO6 distorted octahedral coordination geometry around the zinc ions. Meanwhile, fluorescent properties of the three complexes were investigated at room temperature. The fluorescence spectroscopic analysis demonstrated that the ligand POA shows red-shift after coordinating with the zinc(Ⅱ) ions.
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Innovation and Entrepreneurship Project for College Students in Changsha Medical University,Changsha Medical Education 2022(Project No.41-149)。
文摘Objective:This investigation delineates the anti-cancer potency of epigallocatechin-3-gallate(EGCG)in an oral cancer mouse model,with a focus on its effect on T-cell activation.Methods:An oral cancer model was established in male Balb/c mice using 4-nitroquinoline 1-oxide(4-NQO).The mice were systematically grouped and administered graded concentrations of EGCG.Key parameters such as body weight,hydration levels,tumor volume,and mass were meticulously tracked.T-cell activity and cytokine expression profiles,focusing on interleukin-2(IL-2),interferon-gamma(IFN-γ),and tumor necrosis factor-alpha(TNF-α),were quantified using ELISA.A comprehensive statistical evaluation included one-way ANOVA,Tukey’s HSD multiple comparison test,and the Kruskal-Wallis non-parametric assessment.Results:EGCG-administered cohorts exhibited a pronounced reduction in tumor size and mass,with the high-dose group showing the greatest efficacy.ELISA findings corroborated a significant increase in T-cell activity and concomitant upregulation of key cytokines,including IL-2,IFN-γ,and TNF-α(P<0.05).Conclusion:This investigation confirms the tumor-suppressive efficacy of EGCG in a murine oral squamous cell carcinoma model.The therapeutic effects of EGCG are mediated through T-cell activation and the upregulation of pivotal cytokine expression,highlighting its potential immunomodulatory role in oral cancer treatment.
基金the National Natural Science Foundation of China (No. 81773045, 31270946)the Medical Science and Technology Project of Henan Province, China (No.201702005).
文摘The gut microbiota plays an essential role in intestinal homeostasis. Recent studies indicated that dysbiosis of the gut microbiome may contribute to the development of many disorders, including colon cancer. However, little is known about the profile of microbial populations during upper gastrointestinal carcinogenesis. In this study, a chemical mutagen, 4-nitroquinoline-1-oxide (4NQO), was used to induce oral and esophageal carcinoma in eight-week old male C57BL/6 mice through their drinking water. The changes in the gut microbiota during oral and esophageal carcinogenesis were investigated through 16S sequencing of DNA extracted from fecal samples. Histological analyses of tissue sections demonstrated various stages of lesions in the tongue and esophagus of mice after 4NQO treatment. There was no significant difference in the diversity of gut microbiota between the 4NQO group and the control group. However, the bacterial composition of gut microbiota was significantly different in the 4NQO group compared with the control group. In conclusion, the current murine model suggests that the gut microbiota may be involved in the occurrence of chemically-induced squamous cell carcinoma in the tongue and esophagus. A better understanding of the definite relationship between the microbiome and upper gastrointestinal carcinogenesis might provide potential targets for the prevention and treatment of related diseases.
