Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have un...Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.展开更多
Plants are capable of regulating their shoot architecture in response to diverse internal and external environments.The circadian clock is an adaptive mechanism that integrates information from internal and ambient co...Plants are capable of regulating their shoot architecture in response to diverse internal and external environments.The circadian clock is an adaptive mechanism that integrates information from internal and ambient conditions to help plants cope with recurring environmental fluctuations.Despite the current understanding of plant circadian clock and genetic framework underlying plant shoot architecture,the intricate connection between these two adaptive mechanisms remains largely unclear.In this study,we elucidated how the core clock gene LUX ARRHYTHMO(LUX)regulates shoot architecture in the model legume plant Medicago truncatula.We show that mtlux mutant displays increased main stem height,reduced lateral shoot length,and decreased the number of lateral branches and biomass yield.Gene expression analysis revealed that Mt LUX regulated shoot architecture by repressing the expression of strigolactone receptor MtD14 and MtTB1/MtTCP1A,a TCP gene that functions centrally in modulating shoot architecture.In vivo and in vitro experiments showed that Mt LUX directly binds to a cis-element in the promoter of MtTB1/MtTCP1A,suggesting that Mt LUX regulates branching by rhythmically suppressing MtTB1/MtTCP1A.This work demonstrates the regulatory effect of the circadian clock on shoot architecture,offering a new understanding underlying the genetic basis towards the flexibility of plant shoot architecture.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
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
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
The circadian clock plays a critical role in the regulation of host immune defense.However,the mechanistic basis for this regulation is largely unknown.Herein,the core clock gene cryptochromel(cryl)knockout line in Bo...The circadian clock plays a critical role in the regulation of host immune defense.However,the mechanistic basis for this regulation is largely unknown.Herein,the core clock gene cryptochromel(cryl)knockout line in Bombyx mori,an invertebrate animal model,was constructed to obtain the silkworm with dysfunctional molecular clock,and the dynamic regulation of the circadian clock on the immune responsiveness within 24h of Staphylococcus aureus infection was analyzed.We found that deletion of cryl decreased viability of silkworms and significantly reduced resistance of larvae to S.aureus.Time series RNA-seq analysis identified thousands of rhythmically expressed genes,including immune response genes,in the larval immune tissue,fat bodies.Uninfected cry1 knockout silkworms exhibited expression patterns of rhythmically expressed genes similar to wild-type(WT)silkworms infected with S.aureus.However,cry knockout silkworms exhibited a seriously weakened response to S.aureus infection.The immune response peaked at 6 and 24 h after infection,during which“transcription storms”occurred,and the expression levels of the immune response genes,PGRP and antimicrobial peptides(AMPs),were significantly upregulated in WT.In contrast,cry I knockout did not effectively activate Toll,Imd,or NF-κB signaling pathways during the immune adjustment period from 12 to 18 h after infection,resulting in failure to initiate the immune responsiveness peak at 24 h after infection.This may be related to inhibited silkworm fat body energy metabolism.These results demonstrated the dynamic regulation of circadian clock on silkworm immune response to bacterial infection and provided important insights into hostantimicrobial defensemechanisms.展开更多
Almost all organisms exhibit ~24-h rhythms, or circadian rhythms, in a plentitude of biological processes.These rhythms are driven by endogenous molecular clocks consisting of a series of transcriptional and translati...Almost all organisms exhibit ~24-h rhythms, or circadian rhythms, in a plentitude of biological processes.These rhythms are driven by endogenous molecular clocks consisting of a series of transcriptional and translational feedback loops. Previously, we have shown that the inner nuclear membrane protein MAN1 regulates this clock and thus the locomotor rhythm in flies, but the mechanism remains unclear. Here, we further confirmed the previous findings and found that knocking down MAN1 in the pacemaker neurons of adult flies is sufficient to lengthen the period of the locomotor rhythm. Molecular analysis revealed that knocking down MAN1 led to reduced m RNA and protein levels of the core clock gene period(per),likely by reducing its transcription. Over-expressing per rescued the long period phenotype caused by MAN1 deficiency whereas per mutation had an epistatic effect on MAN1, indicating that MAN1 sets the pace of the clock by targeting per.展开更多
Objective To understand the effects of clock gene BMAL1 and HIF-1α(Hypoxia inducible factor-1α)on proliferation,migration and sensitivity to radiotherapy of nasopharyngeal carcinoma cells HONE1.At the same time,whet...Objective To understand the effects of clock gene BMAL1 and HIF-1α(Hypoxia inducible factor-1α)on proliferation,migration and sensitivity to radiotherapy of nasopharyngeal carcinoma cells HONE1.At the same time,whether the biological clock gene BMAL1 can affect the expression of HIF-1αprotein was investigated.It will lay the foundation for further study on the correlation between clock gene BMAL1 and HIF pathway.Methods BMAL1 gene overexpression and interference lentivirus and HIF-1αgene interference lentivirus were constructed respectively,and were transfected into nasopharyngeal carcinoma cells HONE1.Western blot was used to verify the establishment of overexpressed and knockdown BMAL1 cell lines and HIF-1αgene knockdown cell line,and to investigate the expression of HIF-1αprotein in overexpressed and knockdown BMAL1 cell lines.CCK-8 cell proliferation test and scratch test were used to analyze the proliferation and migration ability of cells.Cell apoptosis after radiotherapy was analyzed by flow cytometry.The effects of BMAL1 and HIF-1αon the sensitivity of HONE1 radiotherapy in nasopharyngeal carcinoma cells after X-ray irradiation at different doses(0Gy,2Gy,4Gy,6Gy)were detected by clone formation assay.Results The overexpression of BMAL1 gene and lentivirus interference were constructed to effectively up regulate and down regulate the expression of BMAL1 protein in nasopharyngeal carcinoma cells HONE1.Meanwhile,HIF-1αgene interference lentivirus was constructed to effectively down-regulate the expression of HIF-1αprotein in nasopharyngeal carcinoma cell line HONE1,and successfully screen out stable nasopharyngeal carcinoma cell lines.Western blot results showed that overexpression of BMAL1 gene could inhibit the expression of HIF-1αprotein in HONE1 of nasopharyngeal carcinoma cells,while knockdown of BMAL1 gene promoted the expression of HIF-1αprotein in HONE1 of nasopharyngeal carcinoma cells(P<0.05).CCK-8 cell proliferation and scratch test showed that overexpression of BMAL1 gene or knockdown of HIF-1αgene could inhibit the proliferation and migration of HONE1 cells(P<0.05).Flow cytometry results showed that after 8Gy irradiation for 72 h,the apoptosis rate of BMALl gene overexpression group was higher than that of the overexpression control group,similarly,the apoptosis rate of HIF-1αgene knockdown group was higher than that of the knockdown control group(P<0.05).After X-ray irradiation at different doses(0Gy,2Gy,4Gy,6Gy),clon-formation experiment showed that the clon-formation rate and cell survival fraction of BMALl overexpression group or HIF-1αknockdown group were lower than those of negative control group(P<0.05).Sigmaplot analysis showed that the D0,Dq and SF2 of the BMAL1 overexpression group or HIF-1αknockdown group were lower than those of the negative control group,and the radiosensitization ratios were 1.381 and 1.063,respectively.Conclusion Overexpression of BMAL1 gene can inhibit the proliferation and migration of nasopharyngeal carcinoma cell line HONE1,increase apoptosis after radiotherapy and improve radiosensitivity.Knock down HIF-1αGene can inhibit the proliferation and migration of nasopharyngeal carcinoma cell line HONE1,increase apoptosis after radiotherapy and improve radiosensitivity.In nasopharyngeal carcinoma cells HONE1,overexpression of BMAL1 gene can inhibit the expression of HIF-1αprotein while knockdown of BMAL1 gene can promote the expression of HIF-1αprotein.展开更多
The circadian clock entrained by environmental light-dark cycles enables plants to fine-tune diurnal growth and developmental responses.Here,we show that physical interactions among evening clock components,including ...The circadian clock entrained by environmental light-dark cycles enables plants to fine-tune diurnal growth and developmental responses.Here,we show that physical interactions among evening clock components,including PSEUDO-RESPONSE REGULATOR 5(PRR5),TIMING OF CAB EXPRESSION 1(TOC1),and the Evening Complex(EC)component EARLY FLOWERING 3(ELF3),define a diurnal repressive chromatin structure specifically at the PHYTOCHROME-INTERACTING FACTOR 4(PIF4)locus in Arabidopsis.These three clock components act interdependently as well as independently to repress nighttime hypocotyl elongation,as hypocotyl elongation rate dramatically increased specifically at nighttime in the prr5-1 toc1-21 elf3-1 mutant,concomitantly with a substantial increase in PIF4 expression.Transcriptional repression of PIF4 by ELF3,PRR5,and TOC1 is mediated by the SWI2/SNF2-RELATED(SWR1)chromatin remodeling complex,which incorporates histone H2A.Z at thePIF4 locus,facilitating robust epigenetic suppression ofPIF4 during the evening.Overall,these findings demonstrate that the PRR-EC-SWR1 complex represses hypocotyl elongation at night through a distinctive chromatin domain covering PIF4 chromatin.展开更多
Adrenocorticotropin hormone (ACTH), which is secreted in response to psychological stress, plays an important role in the hair cycle. This study examined the mechanism by which ACTH affects the hair cycle using mice d...Adrenocorticotropin hormone (ACTH), which is secreted in response to psychological stress, plays an important role in the hair cycle. This study examined the mechanism by which ACTH affects the hair cycle using mice deficient in melanocortin receptor-2(MC2R<sup>-/-</sup>), which is a main receptor for ACTH. We observed the hair cycle using female MC2R<sup>-/-</sup> mice at 15 weeks old and five days old to determine whether there were any age-dependent differences. The 15-week-old MC2R<sup>-/-</sup> mice showed the anagen phase for all mice. On the other hand, all of the MC2R<sup>+/+</sup> mice showed the telogen phase at the same age. Moreover, in the five-day-old mice, the hair growth of the MC2R<sup>-/-</sup> mice occurred earlier than in the MC2R<sup>+/+</sup> mice. Both the 15-week-old and five-day-old MC2R<sup>-/-</sup> mice had higher levels of ACTH and alpha-melanocyte stimulating hormone in the blood than did the MC2R<sup>+/+</sup> mice. In addition, in the 15-week-old MC2R<sup>-/-</sup> mice, the hair cycle shifted to the telogen phase following the administration of a cyclic guanosine monophosphate (cGMP) inhibitor and MC1R/MC5R inhibitor. In the five-day-old MC2R<sup>-/-</sup> mice, the hair growth was slowed by the administration of corticosterone. These results suggest that the ACTH/MC2R system has an important role in the hair cycle.展开更多
基金supported by National Council of Science and Technology(CONACYT)(grants FC 2016/2672 and FOSISS 272757),INMEGEN(09/2017/I)the Ministry of Education,Science,Technology and Innovation of Mexico City(SECTEI)(grant 228/2021).
文摘Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.
基金supported by Laboratory of Lingnan Modern Agriculture Project(NZ2021001)State Key Laboratory for Conservation and Utilization of Subtropical Agrobioresources(SKICUSA-a202007)Natural Science Foundation of Guangdong Province(2022A1515011027,2019A1515012009)。
文摘Plants are capable of regulating their shoot architecture in response to diverse internal and external environments.The circadian clock is an adaptive mechanism that integrates information from internal and ambient conditions to help plants cope with recurring environmental fluctuations.Despite the current understanding of plant circadian clock and genetic framework underlying plant shoot architecture,the intricate connection between these two adaptive mechanisms remains largely unclear.In this study,we elucidated how the core clock gene LUX ARRHYTHMO(LUX)regulates shoot architecture in the model legume plant Medicago truncatula.We show that mtlux mutant displays increased main stem height,reduced lateral shoot length,and decreased the number of lateral branches and biomass yield.Gene expression analysis revealed that Mt LUX regulated shoot architecture by repressing the expression of strigolactone receptor MtD14 and MtTB1/MtTCP1A,a TCP gene that functions centrally in modulating shoot architecture.In vivo and in vitro experiments showed that Mt LUX directly binds to a cis-element in the promoter of MtTB1/MtTCP1A,suggesting that Mt LUX regulates branching by rhythmically suppressing MtTB1/MtTCP1A.This work demonstrates the regulatory effect of the circadian clock on shoot architecture,offering a new understanding underlying the genetic basis towards the flexibility of plant shoot architecture.
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.
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.
基金supported by the National Natural Science Foundation of China(Grant No.32172794 to S.-Q.X.and 31760713 to Y.-J.W.)China Postdoctoral Science Foundation(Grant No.2021M692343 to J.-F.Q.)+2 种基金Nantong Science and Technology(Grant No.JC2021073 to J.-F.Q.)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD to S.-Q.X.)the China Agriculture Research System of MOF and MARA(Grant No.CARS-18-ZJ0103 to Y.-H.S.)。
文摘The circadian clock plays a critical role in the regulation of host immune defense.However,the mechanistic basis for this regulation is largely unknown.Herein,the core clock gene cryptochromel(cryl)knockout line in Bombyx mori,an invertebrate animal model,was constructed to obtain the silkworm with dysfunctional molecular clock,and the dynamic regulation of the circadian clock on the immune responsiveness within 24h of Staphylococcus aureus infection was analyzed.We found that deletion of cryl decreased viability of silkworms and significantly reduced resistance of larvae to S.aureus.Time series RNA-seq analysis identified thousands of rhythmically expressed genes,including immune response genes,in the larval immune tissue,fat bodies.Uninfected cry1 knockout silkworms exhibited expression patterns of rhythmically expressed genes similar to wild-type(WT)silkworms infected with S.aureus.However,cry knockout silkworms exhibited a seriously weakened response to S.aureus infection.The immune response peaked at 6 and 24 h after infection,during which“transcription storms”occurred,and the expression levels of the immune response genes,PGRP and antimicrobial peptides(AMPs),were significantly upregulated in WT.In contrast,cry I knockout did not effectively activate Toll,Imd,or NF-κB signaling pathways during the immune adjustment period from 12 to 18 h after infection,resulting in failure to initiate the immune responsiveness peak at 24 h after infection.This may be related to inhibited silkworm fat body energy metabolism.These results demonstrated the dynamic regulation of circadian clock on silkworm immune response to bacterial infection and provided important insights into hostantimicrobial defensemechanisms.
基金supported by grants from the National Natural Science Foundation of China (31471125 and 31671215)‘‘1000 Talents’’ Program of China
文摘Almost all organisms exhibit ~24-h rhythms, or circadian rhythms, in a plentitude of biological processes.These rhythms are driven by endogenous molecular clocks consisting of a series of transcriptional and translational feedback loops. Previously, we have shown that the inner nuclear membrane protein MAN1 regulates this clock and thus the locomotor rhythm in flies, but the mechanism remains unclear. Here, we further confirmed the previous findings and found that knocking down MAN1 in the pacemaker neurons of adult flies is sufficient to lengthen the period of the locomotor rhythm. Molecular analysis revealed that knocking down MAN1 led to reduced m RNA and protein levels of the core clock gene period(per),likely by reducing its transcription. Over-expressing per rescued the long period phenotype caused by MAN1 deficiency whereas per mutation had an epistatic effect on MAN1, indicating that MAN1 sets the pace of the clock by targeting per.
基金supported in part by grants from the National Natural Science Foundation of China under grant number 82060556,81560437the Department of Science and Technology,Guizhou Province,under grant number[2018]2755+3 种基金the Ordinary Colleges and Universities Youth Science and Technology Talent Growth Project,Guizhou Province,under grant number[2021]187The Health Commission Science and Technology Fund,Guizhou Provincial under grant number gzwkj2021-050Guizhou Medical University 2021 National Foundation Cultivation Project[20NSP041]the Hospital-level Science and Technology Project of Guizhou Cancer Hospital under grant number YJ2019-33.
文摘Objective To understand the effects of clock gene BMAL1 and HIF-1α(Hypoxia inducible factor-1α)on proliferation,migration and sensitivity to radiotherapy of nasopharyngeal carcinoma cells HONE1.At the same time,whether the biological clock gene BMAL1 can affect the expression of HIF-1αprotein was investigated.It will lay the foundation for further study on the correlation between clock gene BMAL1 and HIF pathway.Methods BMAL1 gene overexpression and interference lentivirus and HIF-1αgene interference lentivirus were constructed respectively,and were transfected into nasopharyngeal carcinoma cells HONE1.Western blot was used to verify the establishment of overexpressed and knockdown BMAL1 cell lines and HIF-1αgene knockdown cell line,and to investigate the expression of HIF-1αprotein in overexpressed and knockdown BMAL1 cell lines.CCK-8 cell proliferation test and scratch test were used to analyze the proliferation and migration ability of cells.Cell apoptosis after radiotherapy was analyzed by flow cytometry.The effects of BMAL1 and HIF-1αon the sensitivity of HONE1 radiotherapy in nasopharyngeal carcinoma cells after X-ray irradiation at different doses(0Gy,2Gy,4Gy,6Gy)were detected by clone formation assay.Results The overexpression of BMAL1 gene and lentivirus interference were constructed to effectively up regulate and down regulate the expression of BMAL1 protein in nasopharyngeal carcinoma cells HONE1.Meanwhile,HIF-1αgene interference lentivirus was constructed to effectively down-regulate the expression of HIF-1αprotein in nasopharyngeal carcinoma cell line HONE1,and successfully screen out stable nasopharyngeal carcinoma cell lines.Western blot results showed that overexpression of BMAL1 gene could inhibit the expression of HIF-1αprotein in HONE1 of nasopharyngeal carcinoma cells,while knockdown of BMAL1 gene promoted the expression of HIF-1αprotein in HONE1 of nasopharyngeal carcinoma cells(P<0.05).CCK-8 cell proliferation and scratch test showed that overexpression of BMAL1 gene or knockdown of HIF-1αgene could inhibit the proliferation and migration of HONE1 cells(P<0.05).Flow cytometry results showed that after 8Gy irradiation for 72 h,the apoptosis rate of BMALl gene overexpression group was higher than that of the overexpression control group,similarly,the apoptosis rate of HIF-1αgene knockdown group was higher than that of the knockdown control group(P<0.05).After X-ray irradiation at different doses(0Gy,2Gy,4Gy,6Gy),clon-formation experiment showed that the clon-formation rate and cell survival fraction of BMALl overexpression group or HIF-1αknockdown group were lower than those of negative control group(P<0.05).Sigmaplot analysis showed that the D0,Dq and SF2 of the BMAL1 overexpression group or HIF-1αknockdown group were lower than those of the negative control group,and the radiosensitization ratios were 1.381 and 1.063,respectively.Conclusion Overexpression of BMAL1 gene can inhibit the proliferation and migration of nasopharyngeal carcinoma cell line HONE1,increase apoptosis after radiotherapy and improve radiosensitivity.Knock down HIF-1αGene can inhibit the proliferation and migration of nasopharyngeal carcinoma cell line HONE1,increase apoptosis after radiotherapy and improve radiosensitivity.In nasopharyngeal carcinoma cells HONE1,overexpression of BMAL1 gene can inhibit the expression of HIF-1αprotein while knockdown of BMAL1 gene can promote the expression of HIF-1αprotein.
基金supported by the Basic Science Research(NRF2022R1A2B5B02001266 to P.J.S.and NRF-2023R1A2C3002386 to E.O.)Basic Research Laboratory(NRF-2022R1A4A3024451)programs provided by the National Research Foundation of Korea.
文摘The circadian clock entrained by environmental light-dark cycles enables plants to fine-tune diurnal growth and developmental responses.Here,we show that physical interactions among evening clock components,including PSEUDO-RESPONSE REGULATOR 5(PRR5),TIMING OF CAB EXPRESSION 1(TOC1),and the Evening Complex(EC)component EARLY FLOWERING 3(ELF3),define a diurnal repressive chromatin structure specifically at the PHYTOCHROME-INTERACTING FACTOR 4(PIF4)locus in Arabidopsis.These three clock components act interdependently as well as independently to repress nighttime hypocotyl elongation,as hypocotyl elongation rate dramatically increased specifically at nighttime in the prr5-1 toc1-21 elf3-1 mutant,concomitantly with a substantial increase in PIF4 expression.Transcriptional repression of PIF4 by ELF3,PRR5,and TOC1 is mediated by the SWI2/SNF2-RELATED(SWR1)chromatin remodeling complex,which incorporates histone H2A.Z at thePIF4 locus,facilitating robust epigenetic suppression ofPIF4 during the evening.Overall,these findings demonstrate that the PRR-EC-SWR1 complex represses hypocotyl elongation at night through a distinctive chromatin domain covering PIF4 chromatin.
文摘Adrenocorticotropin hormone (ACTH), which is secreted in response to psychological stress, plays an important role in the hair cycle. This study examined the mechanism by which ACTH affects the hair cycle using mice deficient in melanocortin receptor-2(MC2R<sup>-/-</sup>), which is a main receptor for ACTH. We observed the hair cycle using female MC2R<sup>-/-</sup> mice at 15 weeks old and five days old to determine whether there were any age-dependent differences. The 15-week-old MC2R<sup>-/-</sup> mice showed the anagen phase for all mice. On the other hand, all of the MC2R<sup>+/+</sup> mice showed the telogen phase at the same age. Moreover, in the five-day-old mice, the hair growth of the MC2R<sup>-/-</sup> mice occurred earlier than in the MC2R<sup>+/+</sup> mice. Both the 15-week-old and five-day-old MC2R<sup>-/-</sup> mice had higher levels of ACTH and alpha-melanocyte stimulating hormone in the blood than did the MC2R<sup>+/+</sup> mice. In addition, in the 15-week-old MC2R<sup>-/-</sup> mice, the hair cycle shifted to the telogen phase following the administration of a cyclic guanosine monophosphate (cGMP) inhibitor and MC1R/MC5R inhibitor. In the five-day-old MC2R<sup>-/-</sup> mice, the hair growth was slowed by the administration of corticosterone. These results suggest that the ACTH/MC2R system has an important role in the hair cycle.
