Cells are constantly subjected to cytotoxic and genotoxic insults resulting in the accumulation of unrepaired damaged DNA,which leads to neuronal death.In this way,DNA damage has been implicated in the pathogenesis of...Cells are constantly subjected to cytotoxic and genotoxic insults resulting in the accumulation of unrepaired damaged DNA,which leads to neuronal death.In this way,DNA damage has been implicated in the pathogenesis of neurological disorders,cancer,and aging.Lifestyle factors,such as physical exercise,are neuroprotective and increase brain function by improving cognition,learning,and memory,in addition to regulating the cellular redox milieu.Several mechanisms are associated with the effects of exercise in the brain,such as reduced production of oxidants,up-regulation of antioxidant capacity,and a consequent decrease in nuclear DNA damage.Furthermore,physical exercise is a potential strategy for further DNA damage repair.However,the neuroplasticity molecules that respond to different aspects of physical exercise remain unknown.In this review,we discuss the influence of exercise on DNA damage and adjacent mechanisms in the brain.We discuss the results of several studies that focus on the effects of physical exercise on brain DNA damage.展开更多
Objective To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats. Methods PM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples we...Objective To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats. Methods PM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples were endotracheally instilled into rats. Activity of reduced glutathione peroxidase （GSH-Px） and concentration of malondialdehyde （MDA） were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. DNA migration length （μm） and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. Results The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days. In peripheral blood, the concentration of MDA decreased, but the activity of GSH-Px increased 7 and 14 days after experiments. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. The DNA migration length （μm） and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. Conclusion PM2.5 has a definite oxidative effect on lung tissue and peripheral blood. The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5. The DNA migration length （μm） and rate of tail are simple and valuable biomarkers of PM2 5-induced DNA damage in lung tissues and peripheral blood. The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.展开更多
To repair the damaged SiC coated C/C composites,a double-layer system including a Sm-doped boro-silicate glass external layer and a SieSiC inner layer was prepared by a slurry-based laser cladding technique.Isothermal...To repair the damaged SiC coated C/C composites,a double-layer system including a Sm-doped boro-silicate glass external layer and a SieSiC inner layer was prepared by a slurry-based laser cladding technique.Isothermal oxidation experiment and indirect/direct thermal-radiation measurements were performed.The results showed that the absorbance of borosilicate glass to the laser at 900e1200 nm was improved significantly by Sm-doping.Consequently,the repaired coating with a more compact structure and better oxidation resistance was obtained.After oxidation at 1773 K for 10 h,the mass loss of the damaged sample could be reduced by 74.98%with repairing.By increasing laser-absorption and reducing viscosity,the thermal-radiation property of the repaired coating was enhanced to decrease the surface temperature greatly.A repair system with excellent thermal protection performance was achieved.展开更多
Bacteria with functional DNA repair systems are expected to have low mutation rates due to strong natural selection for genomic stability.However,our study of the wild-type Streptococcus pneumoniae D39,a pathogen resp...Bacteria with functional DNA repair systems are expected to have low mutation rates due to strong natural selection for genomic stability.However,our study of the wild-type Streptococcus pneumoniae D39,a pathogen responsible for many common diseases,revealed a high spontaneous mutation rate of 0.02 per genome per cell division in mutation-accumulation(MA)lines.This rate is orders of magnitude higher than that of other non-mutator bacteria and is characterized by a high mutation bias in the A/T direction.The high mutation rate may have resulted from a reduction in the overall efficiency of selection,conferred by the tiny effective population size in nature.In line with this,S.pneumoniae D39 also exhibited the lowest DNA mismatch-repair(MMR)efficiency among bacteria.Treatment with the antibiotic penicillin did not elevate the mutation rate,as penicillin did not induce DNA damage and S.pneumoniae lacks a stress response pathway.Our findings suggested that the MA results are applicable to within-host scenarios and provide insights into pathogen evolution.展开更多
Humans are daily exposed to background radiation and various sources of oxidative stress. My research has focused in the last 12 years on the effects of ionizing radiation on DNA, which is considered as the key target...Humans are daily exposed to background radiation and various sources of oxidative stress. My research has focused in the last 12 years on the effects of ionizing radiation on DNA, which is considered as the key target of radiation in the cell. Ionizing radiation and endogenous cellular oxidative stress can also induce closely spaced oxidatively induced DNA lesions called "clusters" of DNA damage or locally multiply damage sites, as first introduced by John Ward. I am now interested in the repair mechanisms of clustered DNA damage, which is considered as the most difficult for the cell to repair. A main part of my research is devoted to evaluating the role of clustered DNA damage in the promotion of carcinogenesis in vitro and in vivo . Currently in my laboratory, there are two main ongoing projects. (1) Study of the role of BRCA1 and DNA-dependent protein kinase catalytic subunit repair proteins in the processing of clustered DNA damage in human cancer cells. For this project, we use several tumor cell lines, such as breast cancer cell lines MCF-7 and HCC1937 (BRCA1 deficient) and human glioblastoma cells MO59J/K; and (2) Possible use of DNA damage clusters as novel cancer biomarkers for prognostic and therapeutic applications related to modulation of oxidative stress. In this project human tumor and mice tissues are being used.展开更多
Cancer cells,in which the RAS and PI3K pathways are activated,produce high levels of reactive oxygen species(ROS),which cause oxidative DNA damage and ultimately cellular senescence.This process has been documented in...Cancer cells,in which the RAS and PI3K pathways are activated,produce high levels of reactive oxygen species(ROS),which cause oxidative DNA damage and ultimately cellular senescence.This process has been documented in tissue culture,mouse models,and human pre-cancerous lesions.In this context,cellular senescence functions as a tumour suppressor mechanism.Some rare cancer cells,however,manage to adapt to avoid senescence and continue to proliferate.One well-documented mode of adaptation involves increased production of antioxidants often associated with inactivation of the KEAP1 tumour suppressor gene and the resulting upregulation of the NRF2 transcription factor.In this review,we detail an alternative mode of adaptation to oxidative DNA damage induced by ROS:the increased activity of the base excision repair(BER)pathway,achieved through the enhanced expression of BER enzymes and DNA repair accessory factors.These proteins,exemplified here by the CUT domain proteins CUX1,CUX2,and SATB1,stimulate the activity of BER enzymes.The ensued accelerated repair of oxidative DNA damage enables cancer cells to avoid senescence despite high ROS levels.As a by-product of this adaptation,these cancer cells exhibit increased resistance to genotoxic treatments including ionizing radiation,temozolomide,and cisplatin.Moreover,considering the intrinsic error rate associated with DNA repair and translesion synthesis,the elevated number of oxidative DNA lesions caused by high ROS leads to the accumulation of mutations in the cancer cell population,thereby contributing to tumour heterogeneity and eventually to the acquisition of resistance,a major obstacle to clinical treatment.展开更多
对铈铁掺杂铌酸锂(Ce:Fe:Li Nb O_3)晶体进行氧化、还原处理。通过红外光谱、紫外可见吸收光谱测试了晶体样品的组成和缺陷结构。采用透射光斑畸变法测试了晶体样品的抗光损伤能力,结果表明:生长态晶体比还原态晶体的抗光致散射能力基...对铈铁掺杂铌酸锂(Ce:Fe:Li Nb O_3)晶体进行氧化、还原处理。通过红外光谱、紫外可见吸收光谱测试了晶体样品的组成和缺陷结构。采用透射光斑畸变法测试了晶体样品的抗光损伤能力,结果表明:生长态晶体比还原态晶体的抗光致散射能力基本上高一个数量级,氧化态的晶体要比还原态的晶体高两个数量级。采用二波耦合实验测试了晶体样品的光折变性能,结果表明:从氧化到生长再到还原态,衍射效率逐渐降低,响应时间缩短,光折变灵敏度增加,动态范围逐渐降低。展开更多
文摘Cells are constantly subjected to cytotoxic and genotoxic insults resulting in the accumulation of unrepaired damaged DNA,which leads to neuronal death.In this way,DNA damage has been implicated in the pathogenesis of neurological disorders,cancer,and aging.Lifestyle factors,such as physical exercise,are neuroprotective and increase brain function by improving cognition,learning,and memory,in addition to regulating the cellular redox milieu.Several mechanisms are associated with the effects of exercise in the brain,such as reduced production of oxidants,up-regulation of antioxidant capacity,and a consequent decrease in nuclear DNA damage.Furthermore,physical exercise is a potential strategy for further DNA damage repair.However,the neuroplasticity molecules that respond to different aspects of physical exercise remain unknown.In this review,we discuss the influence of exercise on DNA damage and adjacent mechanisms in the brain.We discuss the results of several studies that focus on the effects of physical exercise on brain DNA damage.
基金supported by National Natural Scientific Foundation (No. 90406024)the Natural Science Fund of Tianjin (No. 023606611)
文摘Objective To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats. Methods PM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples were endotracheally instilled into rats. Activity of reduced glutathione peroxidase （GSH-Px） and concentration of malondialdehyde （MDA） were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. DNA migration length （μm） and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. Results The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days. In peripheral blood, the concentration of MDA decreased, but the activity of GSH-Px increased 7 and 14 days after experiments. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. The DNA migration length （μm） and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. Conclusion PM2.5 has a definite oxidative effect on lung tissue and peripheral blood. The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5. The DNA migration length （μm） and rate of tail are simple and valuable biomarkers of PM2 5-induced DNA damage in lung tissues and peripheral blood. The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.
基金This work has been supported by National Natural Science Foundations of China(grant numbers:51772247,51727804,91860203)Creative Research Foundation of Science and Technology on Thermostructural Composite Materials Laboratory(grant number:JCKYS2019607002).
文摘To repair the damaged SiC coated C/C composites,a double-layer system including a Sm-doped boro-silicate glass external layer and a SieSiC inner layer was prepared by a slurry-based laser cladding technique.Isothermal oxidation experiment and indirect/direct thermal-radiation measurements were performed.The results showed that the absorbance of borosilicate glass to the laser at 900e1200 nm was improved significantly by Sm-doping.Consequently,the repaired coating with a more compact structure and better oxidation resistance was obtained.After oxidation at 1773 K for 10 h,the mass loss of the damaged sample could be reduced by 74.98%with repairing.By increasing laser-absorption and reducing viscosity,the thermal-radiation property of the repaired coating was enhanced to decrease the surface temperature greatly.A repair system with excellent thermal protection performance was achieved.
基金financially supported by Laoshan Laboratory(LSKJ202203203)the National Natural Science Founda-tion of China(31961123002,32270435)+4 种基金the Fundamental Research Funds for the Central Universities of China(202041001)the Shan-dong Provincial Natural Science Foundation(ZR2023QC191)the Postdoctoral Fellowship Program of CPSF under Grant Number GZC20232504the Multidisciplinary University Research Initiative Award from the US Army Research Office(W911NF-09-1-0444)National Institutes of Health award(R35-GM122566 to ML)and(R35-GM131767 to MEW).
文摘Bacteria with functional DNA repair systems are expected to have low mutation rates due to strong natural selection for genomic stability.However,our study of the wild-type Streptococcus pneumoniae D39,a pathogen responsible for many common diseases,revealed a high spontaneous mutation rate of 0.02 per genome per cell division in mutation-accumulation(MA)lines.This rate is orders of magnitude higher than that of other non-mutator bacteria and is characterized by a high mutation bias in the A/T direction.The high mutation rate may have resulted from a reduction in the overall efficiency of selection,conferred by the tiny effective population size in nature.In line with this,S.pneumoniae D39 also exhibited the lowest DNA mismatch-repair(MMR)efficiency among bacteria.Treatment with the antibiotic penicillin did not elevate the mutation rate,as penicillin did not induce DNA damage and S.pneumoniae lacks a stress response pathway.Our findings suggested that the MA results are applicable to within-host scenarios and provide insights into pathogen evolution.
文摘Humans are daily exposed to background radiation and various sources of oxidative stress. My research has focused in the last 12 years on the effects of ionizing radiation on DNA, which is considered as the key target of radiation in the cell. Ionizing radiation and endogenous cellular oxidative stress can also induce closely spaced oxidatively induced DNA lesions called "clusters" of DNA damage or locally multiply damage sites, as first introduced by John Ward. I am now interested in the repair mechanisms of clustered DNA damage, which is considered as the most difficult for the cell to repair. A main part of my research is devoted to evaluating the role of clustered DNA damage in the promotion of carcinogenesis in vitro and in vivo . Currently in my laboratory, there are two main ongoing projects. (1) Study of the role of BRCA1 and DNA-dependent protein kinase catalytic subunit repair proteins in the processing of clustered DNA damage in human cancer cells. For this project, we use several tumor cell lines, such as breast cancer cell lines MCF-7 and HCC1937 (BRCA1 deficient) and human glioblastoma cells MO59J/K; and (2) Possible use of DNA damage clusters as novel cancer biomarkers for prognostic and therapeutic applications related to modulation of oxidative stress. In this project human tumor and mice tissues are being used.
基金supported by Canadian Institutes of Health Research(Grants MOP-326694 and MOP-391532)the National Science and Engineering Council(Grant RGPIN-2016-05155)to A.N.
文摘Cancer cells,in which the RAS and PI3K pathways are activated,produce high levels of reactive oxygen species(ROS),which cause oxidative DNA damage and ultimately cellular senescence.This process has been documented in tissue culture,mouse models,and human pre-cancerous lesions.In this context,cellular senescence functions as a tumour suppressor mechanism.Some rare cancer cells,however,manage to adapt to avoid senescence and continue to proliferate.One well-documented mode of adaptation involves increased production of antioxidants often associated with inactivation of the KEAP1 tumour suppressor gene and the resulting upregulation of the NRF2 transcription factor.In this review,we detail an alternative mode of adaptation to oxidative DNA damage induced by ROS:the increased activity of the base excision repair(BER)pathway,achieved through the enhanced expression of BER enzymes and DNA repair accessory factors.These proteins,exemplified here by the CUT domain proteins CUX1,CUX2,and SATB1,stimulate the activity of BER enzymes.The ensued accelerated repair of oxidative DNA damage enables cancer cells to avoid senescence despite high ROS levels.As a by-product of this adaptation,these cancer cells exhibit increased resistance to genotoxic treatments including ionizing radiation,temozolomide,and cisplatin.Moreover,considering the intrinsic error rate associated with DNA repair and translesion synthesis,the elevated number of oxidative DNA lesions caused by high ROS leads to the accumulation of mutations in the cancer cell population,thereby contributing to tumour heterogeneity and eventually to the acquisition of resistance,a major obstacle to clinical treatment.
文摘对铈铁掺杂铌酸锂(Ce:Fe:Li Nb O_3)晶体进行氧化、还原处理。通过红外光谱、紫外可见吸收光谱测试了晶体样品的组成和缺陷结构。采用透射光斑畸变法测试了晶体样品的抗光损伤能力,结果表明:生长态晶体比还原态晶体的抗光致散射能力基本上高一个数量级,氧化态的晶体要比还原态的晶体高两个数量级。采用二波耦合实验测试了晶体样品的光折变性能,结果表明:从氧化到生长再到还原态,衍射效率逐渐降低,响应时间缩短,光折变灵敏度增加,动态范围逐渐降低。
