PM2.5 are fine inhalable particles with diameters that are generally 2.5 micrometers and smaller and are characterized by a small particle size,a large surface area,and a strong toxin absorption ability[1-3].PM2.5 con...PM2.5 are fine inhalable particles with diameters that are generally 2.5 micrometers and smaller and are characterized by a small particle size,a large surface area,and a strong toxin absorption ability[1-3].PM2.5 contains heavy metals and organic pollutants that are harmful to human health and exert carcinogenic,teratogenic,and mutagenic effects[4-7].PM2.5 has been classified as a human carcinogen by the International Agency for Research on Cancer(IARC)[2].The economy has developed rapidly making air pollution a serious environmental health problem in China.The purpose of this study was to explore the differentially expressed genes and pathways after a PM2.5 exposure in the human bronchial epithelial(HBE)cells via gene chip technology and bioinformatics analysis.展开更多
Objective To investigate the effect of c-fos gene silencing on differentially expressed proteins(DEPs) in human bronchial epithelial(HBE) cells after exposure to fine particulate matter(PM2.5).Methods HBE cells and c-...Objective To investigate the effect of c-fos gene silencing on differentially expressed proteins(DEPs) in human bronchial epithelial(HBE) cells after exposure to fine particulate matter(PM2.5).Methods HBE cells and c-fos-silenced HBE cells were exposed to 50 μg/mL PM2.5, LC-MS/MS and tandem mass tag(TMT) labeling methods were combined with bioinformatics methods, and DEPs and interaction networks were identified.Results In the HBE group, 414 DEPs were screened, of which 227 were up-regulated and 187 downregulated. In the c-fos silenced HBE group, 480 DEPs were screened, including 240 up-regulated proteins and 240 down-regulated proteins. KEGG annotations showed that DEPs in the HBE group are mainly concentrated in the glycolysis/gluconeogenesis pathway and those in the c-fos silenced group are concentrated mainly in endoplasmic reticulum and the processing of proteins. Additionally, the abnormal expression of GPRC5 C, DKK4, and UBE2 C was identified in top 15 DEPs. After constructing the protein interaction network, 20 Hub proteins including HNRNPA2 B1, HNRNPL, RPS15 A, and RPS25 were screened from the HBE group and the c-fos silenced HBE group.Conclusion c-fos gene affected the expression of cancer-related proteins. Our results provided a scientific basis for further study of PM2.5-induced carcinogenesis mechanism.展开更多
目的探讨HMGA2基因缺失对PM2.5暴露致大鼠肺损伤和心功能不全的影响。方法将野生型(WT)大鼠按体重用随机数字表法分为对照组和PM2.5组,每组5只大鼠;将HMGA2^(-/-)大鼠按体重用随机数字表法分为HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组,每组...目的探讨HMGA2基因缺失对PM2.5暴露致大鼠肺损伤和心功能不全的影响。方法将野生型(WT)大鼠按体重用随机数字表法分为对照组和PM2.5组,每组5只大鼠;将HMGA2^(-/-)大鼠按体重用随机数字表法分为HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组,每组5只大鼠。对照组和HMGA2^(-/-)组大鼠每天气管滴注0.3 ml 0.9%氯化钠溶液,PM2.5组和HMGA2^(-/-)+PM2.5组每天气管滴注0.3 ml PM2.5混悬液,连续4周后对大鼠的心功能[左心室射血分数(LVEF)、左心室缩短分数(LVFS)]和肺功能[肺活量(FVC)、最大通气量(MVV)]进行评价,检测大鼠血清中白介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、3-硝基酪氨酸(3-NT)和4-羟基壬烯醛(4-HNE)水平,同时检测肺和心脏组织中高迁移率族蛋白A2(HMGA2)、核转录因子-κB(NF-κB)和过氧化物还原判酶5(PRDX5)蛋白水平。结果HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组大鼠肺和心脏组织中HMGA2无表达;与对照组比较,PM2.5组肺和心脏组织中HMGA2表达降低,差异有统计学意义(P<0.05);与对照组比较,HMGA2^(-/-)组各指标差异无统计学意义(P>0.05);与对照组比较,PM2.5组和HMGA2^(-/-)+PM2.5组大鼠FVC、MVV、LVEF和LVFS降低,IL-6、TNF-α、3-NT和4-HNE增加,肺和心脏组织中NF-κB和PRDX5降低(P<0.05);与PM2.5组比较,HMGA2^(-/-)+PM2.5组大鼠FVC、MVV、LVEF和LVFS降低,IL-6、TNF-α、3-NT和4-HNE增加,肺和心脏组织中NF-κB增加、PRDX5降低(P<0.05)。结论HMGA2基因敲除能加重PM2.5暴露致大鼠肺损伤和心功能不全,其机制可能与炎症和氧化应激有关。展开更多
Background Congenital heart disease （CHD） is the most common developmental anomaly in newborns. The germline mutations in GATA4 and NKX2.5 genes have been identified as responsible for CHD. The frequency of GATA4 an...Background Congenital heart disease （CHD） is the most common developmental anomaly in newborns. The germline mutations in GATA4 and NKX2.5 genes have been identified as responsible for CHD. The frequency of GATA4 and NKX2.5 mutations in Chinese Uygur patients with CHD and the correlation between their genotype and CHD phenotype are unknown. Methods We examined the coding region of GATA4 and NKX2,5genes in 62 Chinese Uygur patients with CHD and 117 Chinese Uygur individuals as the controls by denaturing high pedormance liquid chromatography （DHPLC） and sequencing. Results Two heterozygous missense mutations of c.1220C〉A and c.1273G〉A in GATA4 gene, which cause the amino acid residue changes of P407Q and D425N in GATA4, were found in a patient with tetralogy of Fallot and a patient with ventricular septal defect, respectively. The two patients did not have atrioventricular conduct defects or non-cardiac abnormalities. The two mutations are expected to affect the protein function. There were no reported NKX2.5 mutations in the patients. Conclusion Our results provided the primary data on CHD phenotype associated with GATA4 mutation in the Chinese Uygur population.展开更多
Summary Precise replacement of an existing allele in commercial cultivars with an elite allele is a major goal in crop breeding. A single nucleotide polymorphism in the NRT1.1B gene between japonica and indica rice is...Summary Precise replacement of an existing allele in commercial cultivars with an elite allele is a major goal in crop breeding. A single nucleotide polymorphism in the NRT1.1B gene between japonica and indica rice is responsible for the improved nitrogen use efficiency in indica rice. Herein, we precisely replaced the japonica NRT1.1B allele with the indica allele, in just one generation, using CRISPR/Cas9 gene-editing technology. No additional selective pressure was needed to enrich the precise replacement events.展开更多
基金supported by the basic research programs of Shenzhen Science and Technology Innovation Committee to XU Xin Yun [JCYJ20170413101713324].
文摘PM2.5 are fine inhalable particles with diameters that are generally 2.5 micrometers and smaller and are characterized by a small particle size,a large surface area,and a strong toxin absorption ability[1-3].PM2.5 contains heavy metals and organic pollutants that are harmful to human health and exert carcinogenic,teratogenic,and mutagenic effects[4-7].PM2.5 has been classified as a human carcinogen by the International Agency for Research on Cancer(IARC)[2].The economy has developed rapidly making air pollution a serious environmental health problem in China.The purpose of this study was to explore the differentially expressed genes and pathways after a PM2.5 exposure in the human bronchial epithelial(HBE)cells via gene chip technology and bioinformatics analysis.
基金This project was supported by the programs of Shenzhen Science and Technology Innovation Committee to XU Xin Yun[JCYJ20170413101713324,JCYJ20190807102205480]Shenzhen Key Medical Discipline Construction Fund[SZXK067].
文摘Objective To investigate the effect of c-fos gene silencing on differentially expressed proteins(DEPs) in human bronchial epithelial(HBE) cells after exposure to fine particulate matter(PM2.5).Methods HBE cells and c-fos-silenced HBE cells were exposed to 50 μg/mL PM2.5, LC-MS/MS and tandem mass tag(TMT) labeling methods were combined with bioinformatics methods, and DEPs and interaction networks were identified.Results In the HBE group, 414 DEPs were screened, of which 227 were up-regulated and 187 downregulated. In the c-fos silenced HBE group, 480 DEPs were screened, including 240 up-regulated proteins and 240 down-regulated proteins. KEGG annotations showed that DEPs in the HBE group are mainly concentrated in the glycolysis/gluconeogenesis pathway and those in the c-fos silenced group are concentrated mainly in endoplasmic reticulum and the processing of proteins. Additionally, the abnormal expression of GPRC5 C, DKK4, and UBE2 C was identified in top 15 DEPs. After constructing the protein interaction network, 20 Hub proteins including HNRNPA2 B1, HNRNPL, RPS15 A, and RPS25 were screened from the HBE group and the c-fos silenced HBE group.Conclusion c-fos gene affected the expression of cancer-related proteins. Our results provided a scientific basis for further study of PM2.5-induced carcinogenesis mechanism.
文摘目的探讨HMGA2基因缺失对PM2.5暴露致大鼠肺损伤和心功能不全的影响。方法将野生型(WT)大鼠按体重用随机数字表法分为对照组和PM2.5组,每组5只大鼠;将HMGA2^(-/-)大鼠按体重用随机数字表法分为HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组,每组5只大鼠。对照组和HMGA2^(-/-)组大鼠每天气管滴注0.3 ml 0.9%氯化钠溶液,PM2.5组和HMGA2^(-/-)+PM2.5组每天气管滴注0.3 ml PM2.5混悬液,连续4周后对大鼠的心功能[左心室射血分数(LVEF)、左心室缩短分数(LVFS)]和肺功能[肺活量(FVC)、最大通气量(MVV)]进行评价,检测大鼠血清中白介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、3-硝基酪氨酸(3-NT)和4-羟基壬烯醛(4-HNE)水平,同时检测肺和心脏组织中高迁移率族蛋白A2(HMGA2)、核转录因子-κB(NF-κB)和过氧化物还原判酶5(PRDX5)蛋白水平。结果HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组大鼠肺和心脏组织中HMGA2无表达;与对照组比较,PM2.5组肺和心脏组织中HMGA2表达降低,差异有统计学意义(P<0.05);与对照组比较,HMGA2^(-/-)组各指标差异无统计学意义(P>0.05);与对照组比较,PM2.5组和HMGA2^(-/-)+PM2.5组大鼠FVC、MVV、LVEF和LVFS降低,IL-6、TNF-α、3-NT和4-HNE增加,肺和心脏组织中NF-κB和PRDX5降低(P<0.05);与PM2.5组比较,HMGA2^(-/-)+PM2.5组大鼠FVC、MVV、LVEF和LVFS降低,IL-6、TNF-α、3-NT和4-HNE增加,肺和心脏组织中NF-κB增加、PRDX5降低(P<0.05)。结论HMGA2基因敲除能加重PM2.5暴露致大鼠肺损伤和心功能不全,其机制可能与炎症和氧化应激有关。
基金This study was supported by the grants from the National Natural Science Foundation of China （No.30672193） and the National Science Foundation of Beijing （No. Y0204004040231）.The authors are grateful to the subjects for participating in this study. We also thank Dr. BU Ding-fang and Dr. ZHANG Hua for theh technical assistance.
文摘Background Congenital heart disease （CHD） is the most common developmental anomaly in newborns. The germline mutations in GATA4 and NKX2.5 genes have been identified as responsible for CHD. The frequency of GATA4 and NKX2.5 mutations in Chinese Uygur patients with CHD and the correlation between their genotype and CHD phenotype are unknown. Methods We examined the coding region of GATA4 and NKX2,5genes in 62 Chinese Uygur patients with CHD and 117 Chinese Uygur individuals as the controls by denaturing high pedormance liquid chromatography （DHPLC） and sequencing. Results Two heterozygous missense mutations of c.1220C〉A and c.1273G〉A in GATA4 gene, which cause the amino acid residue changes of P407Q and D425N in GATA4, were found in a patient with tetralogy of Fallot and a patient with ventricular septal defect, respectively. The two patients did not have atrioventricular conduct defects or non-cardiac abnormalities. The two mutations are expected to affect the protein function. There were no reported NKX2.5 mutations in the patients. Conclusion Our results provided the primary data on CHD phenotype associated with GATA4 mutation in the Chinese Uygur population.
基金partly funded by the Ministry of Science and Technology of China (2016YFD0102003)the Chinese Ministry of Agriculture (2016ZX 08010003)
文摘Summary Precise replacement of an existing allele in commercial cultivars with an elite allele is a major goal in crop breeding. A single nucleotide polymorphism in the NRT1.1B gene between japonica and indica rice is responsible for the improved nitrogen use efficiency in indica rice. Herein, we precisely replaced the japonica NRT1.1B allele with the indica allele, in just one generation, using CRISPR/Cas9 gene-editing technology. No additional selective pressure was needed to enrich the precise replacement events.
