Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were ra...Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.展开更多
Objective： The aim of this study was to investigate the influence of hepatitis B virus X protein （HBx） on the clock genes in LO2 cells and its significance. Methods： A cell line LO2-HBx, Stably transfected with HB...Objective： The aim of this study was to investigate the influence of hepatitis B virus X protein （HBx） on the clock genes in LO2 cells and its significance. Methods： A cell line LO2-HBx, Stably transfected with HBx gene, was established. The levels of mRNA and protein expression of CLOCK and BMAL1 were detected by real-time PCR and western blot. Resuits： The expression of CLOCK mRNA and protein were increased in cell line LO2-HBx （P 〈 0.05）, while the expression of BMAL1 mRNA and protein were decreased in cell line LO2-HBx （P 〈 0.05）. Conclusion： The expressions of core clock gene CLOCK and BMAL1 have been changed by HBx, which breaks down the previous circadian rhythm of liver cells. This maybe one of the reasons leads to the formation of liver cancer.展开更多
Circadian rhythms are natural rhythms that widely exist in all creatures,and regulate the processes and physiological functions of various biochemical reactions.The circadian clock is critical for cancer occurrence an...Circadian rhythms are natural rhythms that widely exist in all creatures,and regulate the processes and physiological functions of various biochemical reactions.The circadian clock is critical for cancer occurrence and progression.Its function is regulated by metabolic activities,and the expression and transcription of various genes.This review summarizes the composition of the circadian clock;the biological basis for its function;its relationship with,and mechanisms in,cancer;its various functions in different cancers;the effects of anti-tumor treatment;and potential therapeutic targets.Research in this area is expected to advance understanding of circadian locomotor output cycles kaput(CLOCK)and brain and muscle ARNT-like protein 1(BMAL1)in tumor diseases,and contribute to the development of new anti-tumor treatment strategies.展开更多
Immunotherapy has revolutionized cancer treatment by leveraging the intrinsic immune system.Although tremendous attention has focused on developing a new class of drugs enhancing or normalizing anti-tumor immunity,lit...Immunotherapy has revolutionized cancer treatment by leveraging the intrinsic immune system.Although tremendous attention has focused on developing a new class of drugs enhancing or normalizing anti-tumor immunity,little effort was devoted to considering their time-of-day difference of administration in therapeutic efficacy.展开更多
文摘Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.
文摘Objective： The aim of this study was to investigate the influence of hepatitis B virus X protein （HBx） on the clock genes in LO2 cells and its significance. Methods： A cell line LO2-HBx, Stably transfected with HBx gene, was established. The levels of mRNA and protein expression of CLOCK and BMAL1 were detected by real-time PCR and western blot. Resuits： The expression of CLOCK mRNA and protein were increased in cell line LO2-HBx （P 〈 0.05）, while the expression of BMAL1 mRNA and protein were decreased in cell line LO2-HBx （P 〈 0.05）. Conclusion： The expressions of core clock gene CLOCK and BMAL1 have been changed by HBx, which breaks down the previous circadian rhythm of liver cells. This maybe one of the reasons leads to the formation of liver cancer.
基金supported by the National Natural Science Foundation of China(Grant Nos.81621003,32000533,82073059,and 81872020)。
文摘Circadian rhythms are natural rhythms that widely exist in all creatures,and regulate the processes and physiological functions of various biochemical reactions.The circadian clock is critical for cancer occurrence and progression.Its function is regulated by metabolic activities,and the expression and transcription of various genes.This review summarizes the composition of the circadian clock;the biological basis for its function;its relationship with,and mechanisms in,cancer;its various functions in different cancers;the effects of anti-tumor treatment;and potential therapeutic targets.Research in this area is expected to advance understanding of circadian locomotor output cycles kaput(CLOCK)and brain and muscle ARNT-like protein 1(BMAL1)in tumor diseases,and contribute to the development of new anti-tumor treatment strategies.
文摘Immunotherapy has revolutionized cancer treatment by leveraging the intrinsic immune system.Although tremendous attention has focused on developing a new class of drugs enhancing or normalizing anti-tumor immunity,little effort was devoted to considering their time-of-day difference of administration in therapeutic efficacy.
