Objective： Investigation of the effect of Xiaoaiping on the expression of circadian clock genes in human hepatoma HepG2 cells. Methods： Selecting the HepG2 cells in the logarithmic growth phase and assigning them to...Objective： Investigation of the effect of Xiaoaiping on the expression of circadian clock genes in human hepatoma HepG2 cells. Methods： Selecting the HepG2 cells in the logarithmic growth phase and assigning them to Xiaoaiping injection （XAP） group and control group. The two groups were treated with 75 mg/mL XAP or the same dose of normal saline. After 72 h of treatment, real-time PCR was used to detect the expression of circadian clock genes in HepG2 cells and Western Blot technology was used to detect the expression of related proteins. Results： The mRNA expression levels of PER1, NPAS2, NR1D1, and DEC1 in the XAP group was significantly higher than that in the control group （P〈 0.05）, while the mRNA expression levels of PER3, BMAL1, DEC2, and RORA were significantly lower in the XAP group than in the control group （P 〈 0.05）, and there was no significant difference between the mRNA expression levels of PER2, CRY1, CRY2, and TIM. Of course, the proteins＇ expression levels of the genes we had detected such as PERle3, CRYI-2, CLOCK, BMAL1 by Western Blot were consistent with the real-time PCR results above. Conclusion： XAP affects the expression of circadian clock genes in HepG2 cells.展开更多
Objective: To investigate the effects of 72 hours continuous sleep deprivation (SD) on circadian clock gene expression and oxidative stress in the rat liver. Methods: Twenty healthy male Sprague-Dawley rats were divid...Objective: To investigate the effects of 72 hours continuous sleep deprivation (SD) on circadian clock gene expression and oxidative stress in the rat liver. Methods: Twenty healthy male Sprague-Dawley rats were divided into 2 groups (n = 10 each) using a random number table: normal control group (group C), sleep deprivation group (group SD). Group SD was treated with a modified multiple platform water environment method. After 72 hours sleep deprived, the levels of AST (Aspartate transaminase ) and ALT (Alanine aminotransferase) in serum were determined. The contents of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the liver tissue of the rats were examined in both two groups. The expression levels of CLOCK, BMAL1 and CRY1 protein in liver tissue were examined by Western blotting. Results: Compared with group C, the content of MDA, and the levels of AST and ALT in serum were significantly increased (P Conclusion: 72 hours continuous sleep deprivation can downregulate the expression of circadian clock gene and promote oxidative stress in rats.展开更多
Mammalian bone is constantly metabolized from the embryonic stage,and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation,mediated by osteoclasts and osteoblasts.It...Mammalian bone is constantly metabolized from the embryonic stage,and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation,mediated by osteoclasts and osteoblasts.It is widely recognized that circadian clock genes can regulate bone metabolism.In recent years,the regulation of bone metabolism by non-coding RNAs has become a hotspot of research.MicroRNAs can participate in bone catabolism and anabolism by targeting key factors related to bone metabolism,including circadian clock genes.However,research in this field has been conducted only in recent years and the mechanisms involved are not yet well established.Recent studies have focused on how to target circadian clock genes to treat some diseases,such as autoimmune diseases,but few have focused on the co-regulation of circadian clock genes and microRNAs in bone metabolic diseases.Therefore,in this paper we review the progress of research on the co-regulation of bone metabolism by circadian clock genes and microRNAs,aiming to provide new ideas for the prevention and treatment of bone metabolic diseases such as osteoporosis.展开更多
Circadian clocks are endogenous timers that enable plants to synchronize biological processes with daily and seasonal environmental conditions in order to allocate resources during the most beneficial times of day and...Circadian clocks are endogenous timers that enable plants to synchronize biological processes with daily and seasonal environmental conditions in order to allocate resources during the most beneficial times of day and year. The circadian clock regulates a number of central plant activities, including growth, develop- ment, and reproduction, primarily through controlling a substantial proportion of transcriptional activity and protein function. This review examines the roles that alleles of circadian clock genes have played in domestication and improvement of crop plants. The focus here is on three groups of circadian clock genes essential to clock function in Arabidopsis thaliana： PSEUDO-RESPONSE REGULATORs, GIGANTEA, and the evening complex genes EARL Y FLOWERING 3, EARLY FLOWERING 4, and LUX ARRHYTHMO. Homol- ogous genes from each group underlie quantitative trait loci that have beneficial influences on key agricul- tural traits, especially flowering time but also yield, biomass, and biennial growth habit. Emerging insights into circadian clock regulation of other fundamental plant processes, including responses to abiotic and biotic stresses, are discussed to highlight promising avenues for further crop improvement.展开更多
In insects,facultative diapause is a state of developmental arrest mainly induced by photoperiod or temperature that allows insects to survive adverse environmental conditions.Understanding how insect initiates facult...In insects,facultative diapause is a state of developmental arrest mainly induced by photoperiod or temperature that allows insects to survive adverse environmental conditions.Understanding how insect initiates facultative diapause and prepares diapause can provide us new insights to study developmental and evolutionary biology.It has been shown that the circadian clock genes can participate in photoperiodic measurement and regulate reproductive diapause initiation through JH signaling in short-day-induced winter diapause.However,how circadian clock genes translate photoperiodic information into downstream JH signaling for diapause destiny and then affect diapause preparation remains largely unknown.In the present study,we investigate this in the cabbage beetle Colaphellus bowringi which undergoes reproductive diapause under long-day condition.We respectively knocked down two circadian clock negative regulators,period(per)and timeless(tim),in the 3-day-old larvae(most sensitive to photoperiod),and dsgfp treatment was served as a control.Under the diapause-inducing photoperiod(16L:8D),knocking down per and tim significantly decreased the rate of burrowing behavior.And mtany female beetles of the per and tim RNAi showed developed ovary,decreased lipid accumulation and downregulated expression of stress resistance genes.The JHinduced genes,Kr-h1,JHE1,Vg1,and Vg2, significantly increased in the females with suppression of per and tim.It implied that suppression of per and tim during diapause initiation phase(DIP)could activate the JH signaling in the female adults.Before the beetles enter into diapause preparation phase(DPP),we used RNA sequencing to analyize gene expression profiles after per and tim RNAi.It showed that many differentially expressed genes were enriched in environmental information processing,such as mTOR and TGF-beta signaling pathway.To ask whether per and tim also regulate diapause preparation,we knocked down these two genes in the female adults during DPP.It showed that the diapause destiny was not af-fected,but the lipid storage in diapause-destined females was significantly reduced after per and tim RNAi.Interestingly,per-and tim-regulated lipid storage during DPP was independent on JH signaling.We further found that per and tim promoted lipid storage by regulating the expression of genes that control lipogenesis and lipolysis.In summary,these results suggest that per and tim participate in photoperiodic measurement and initiate reproductive diapause through JH signaling during DIP in long-day-induced summer diapause.The mTOR and TGF-beta signaling pathways may be involved in the regulation of JH signaling by circadian clock genes.Meanwhile,per and tim transduce photoperiodic signal and promote lipid storage during DPP in a JH-independent manner.These results provide us new clues to study the molecular mechanism of photoperiod-regulated diapause induction in insects.展开更多
Colorectal cancer is the most prevalent among digestive system cancers.Carcinogenesis relies on disrupted control of cellular processes,such as metabolism,proliferation,DNA damage recognition and repair,and apoptosis....Colorectal cancer is the most prevalent among digestive system cancers.Carcinogenesis relies on disrupted control of cellular processes,such as metabolism,proliferation,DNA damage recognition and repair,and apoptosis.Cell,tissue,organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery.Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis,and altered expression of clock genes has been found in cancer patients.Epidemiological studies have shown that circadian disruption,that is,alteration of bodily temporal organization,is a cancer risk factor,and an increased incidence of colorectal neoplastic disease is reported in shift workers.In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.展开更多
Summary： This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system （RAAS） and clock genes in the kidney. The male Wist...Summary： This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system （RAAS） and clock genes in the kidney. The male Wistar rat models of 5/6 subtotal nephrectomy （STNx） were established. Animals were ran- domly divided into 4 groups： sham STNx group （control）, STNx group, morning benazepril group （MB） and evening benazepril group （EB）. Benazepril was intragastfically administered at a dose of 10 mg/kg/day at 07：00 and 19：00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light：dark cycle of 12：12 for 12 weeks. Systolic blood pressure （SBP）, 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity （RA）, angio- tensin Ⅱ （Ang Ⅱ ） and aldosterone （Aid） by radioimmunoassay （RIA） and the mRNA expression profile of clock genes （bmall, dbp and per2） by real-time PCR at 12 weeks. Our results showed that no signifi- cant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Aid and RA content of a day between the MB group and EB group. The expression peak of bmall mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects.展开更多
文摘Objective： Investigation of the effect of Xiaoaiping on the expression of circadian clock genes in human hepatoma HepG2 cells. Methods： Selecting the HepG2 cells in the logarithmic growth phase and assigning them to Xiaoaiping injection （XAP） group and control group. The two groups were treated with 75 mg/mL XAP or the same dose of normal saline. After 72 h of treatment, real-time PCR was used to detect the expression of circadian clock genes in HepG2 cells and Western Blot technology was used to detect the expression of related proteins. Results： The mRNA expression levels of PER1, NPAS2, NR1D1, and DEC1 in the XAP group was significantly higher than that in the control group （P〈 0.05）, while the mRNA expression levels of PER3, BMAL1, DEC2, and RORA were significantly lower in the XAP group than in the control group （P 〈 0.05）, and there was no significant difference between the mRNA expression levels of PER2, CRY1, CRY2, and TIM. Of course, the proteins＇ expression levels of the genes we had detected such as PERle3, CRYI-2, CLOCK, BMAL1 by Western Blot were consistent with the real-time PCR results above. Conclusion： XAP affects the expression of circadian clock genes in HepG2 cells.
文摘Objective: To investigate the effects of 72 hours continuous sleep deprivation (SD) on circadian clock gene expression and oxidative stress in the rat liver. Methods: Twenty healthy male Sprague-Dawley rats were divided into 2 groups (n = 10 each) using a random number table: normal control group (group C), sleep deprivation group (group SD). Group SD was treated with a modified multiple platform water environment method. After 72 hours sleep deprived, the levels of AST (Aspartate transaminase ) and ALT (Alanine aminotransferase) in serum were determined. The contents of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the liver tissue of the rats were examined in both two groups. The expression levels of CLOCK, BMAL1 and CRY1 protein in liver tissue were examined by Western blotting. Results: Compared with group C, the content of MDA, and the levels of AST and ALT in serum were significantly increased (P Conclusion: 72 hours continuous sleep deprivation can downregulate the expression of circadian clock gene and promote oxidative stress in rats.
基金This work was supported by the National Natural Science Foundation of China(Nos.81901430 and 81871835)the Guangdong Provincial Natural Science Foundation of China(No.2022A1515010379)+1 种基金the Innovation Project from Department of Education of Guangdong Province(No.2021KTSCX 055)the Shanghai Frontiers Science Research Base of Exercise and Metabolic Health,and the Shanghai Key Laboratory for Human Athletic Ability Development and Support(Shanghai University of Sport)(No.11DZ2261100),China.
文摘Mammalian bone is constantly metabolized from the embryonic stage,and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation,mediated by osteoclasts and osteoblasts.It is widely recognized that circadian clock genes can regulate bone metabolism.In recent years,the regulation of bone metabolism by non-coding RNAs has become a hotspot of research.MicroRNAs can participate in bone catabolism and anabolism by targeting key factors related to bone metabolism,including circadian clock genes.However,research in this field has been conducted only in recent years and the mechanisms involved are not yet well established.Recent studies have focused on how to target circadian clock genes to treat some diseases,such as autoimmune diseases,but few have focused on the co-regulation of circadian clock genes and microRNAs in bone metabolic diseases.Therefore,in this paper we review the progress of research on the co-regulation of bone metabolism by circadian clock genes and microRNAs,aiming to provide new ideas for the prevention and treatment of bone metabolic diseases such as osteoporosis.
文摘Circadian clocks are endogenous timers that enable plants to synchronize biological processes with daily and seasonal environmental conditions in order to allocate resources during the most beneficial times of day and year. The circadian clock regulates a number of central plant activities, including growth, develop- ment, and reproduction, primarily through controlling a substantial proportion of transcriptional activity and protein function. This review examines the roles that alleles of circadian clock genes have played in domestication and improvement of crop plants. The focus here is on three groups of circadian clock genes essential to clock function in Arabidopsis thaliana： PSEUDO-RESPONSE REGULATORs, GIGANTEA, and the evening complex genes EARL Y FLOWERING 3, EARLY FLOWERING 4, and LUX ARRHYTHMO. Homol- ogous genes from each group underlie quantitative trait loci that have beneficial influences on key agricul- tural traits, especially flowering time but also yield, biomass, and biennial growth habit. Emerging insights into circadian clock regulation of other fundamental plant processes, including responses to abiotic and biotic stresses, are discussed to highlight promising avenues for further crop improvement.
基金Funded by the National Natural Science Foundation of China(31701842)
文摘In insects,facultative diapause is a state of developmental arrest mainly induced by photoperiod or temperature that allows insects to survive adverse environmental conditions.Understanding how insect initiates facultative diapause and prepares diapause can provide us new insights to study developmental and evolutionary biology.It has been shown that the circadian clock genes can participate in photoperiodic measurement and regulate reproductive diapause initiation through JH signaling in short-day-induced winter diapause.However,how circadian clock genes translate photoperiodic information into downstream JH signaling for diapause destiny and then affect diapause preparation remains largely unknown.In the present study,we investigate this in the cabbage beetle Colaphellus bowringi which undergoes reproductive diapause under long-day condition.We respectively knocked down two circadian clock negative regulators,period(per)and timeless(tim),in the 3-day-old larvae(most sensitive to photoperiod),and dsgfp treatment was served as a control.Under the diapause-inducing photoperiod(16L:8D),knocking down per and tim significantly decreased the rate of burrowing behavior.And mtany female beetles of the per and tim RNAi showed developed ovary,decreased lipid accumulation and downregulated expression of stress resistance genes.The JHinduced genes,Kr-h1,JHE1,Vg1,and Vg2, significantly increased in the females with suppression of per and tim.It implied that suppression of per and tim during diapause initiation phase(DIP)could activate the JH signaling in the female adults.Before the beetles enter into diapause preparation phase(DPP),we used RNA sequencing to analyize gene expression profiles after per and tim RNAi.It showed that many differentially expressed genes were enriched in environmental information processing,such as mTOR and TGF-beta signaling pathway.To ask whether per and tim also regulate diapause preparation,we knocked down these two genes in the female adults during DPP.It showed that the diapause destiny was not af-fected,but the lipid storage in diapause-destined females was significantly reduced after per and tim RNAi.Interestingly,per-and tim-regulated lipid storage during DPP was independent on JH signaling.We further found that per and tim promoted lipid storage by regulating the expression of genes that control lipogenesis and lipolysis.In summary,these results suggest that per and tim participate in photoperiodic measurement and initiate reproductive diapause through JH signaling during DIP in long-day-induced summer diapause.The mTOR and TGF-beta signaling pathways may be involved in the regulation of JH signaling by circadian clock genes.Meanwhile,per and tim transduce photoperiodic signal and promote lipid storage during DPP in a JH-independent manner.These results provide us new clues to study the molecular mechanism of photoperiod-regulated diapause induction in insects.
基金Supported by The"5x1000"voluntary contribution and by a grant to GM from the Italian Ministry of Health through Department of Medical Sciences,Division of Internal Medicine and Chronobiology Unit,IRCCS Scientific Institute and Regional General Hospital"Casa Sollievo della Sofferenza",Opera di Padre Pio da Pietrelcina,San Giovanni Rotondo(FG),Italy,Nos.RC1203ME46 and RC1302ME31by a grant to AP from the Italian Ministry of Health through Department of Medical Sciences,Division of Gastroenterology and Research Laboratory,Nos.RC1203GA55 and RC1203GA56by a grant to MV from AIRC,No.MFAG-AIRC2012-13419
文摘Colorectal cancer is the most prevalent among digestive system cancers.Carcinogenesis relies on disrupted control of cellular processes,such as metabolism,proliferation,DNA damage recognition and repair,and apoptosis.Cell,tissue,organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery.Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis,and altered expression of clock genes has been found in cancer patients.Epidemiological studies have shown that circadian disruption,that is,alteration of bodily temporal organization,is a cancer risk factor,and an increased incidence of colorectal neoplastic disease is reported in shift workers.In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.
基金supported by grants from the Department of Public Health of Hubei Province of China (No. 2012Z-B08)the Health Bureau of Wuhan City of China (No. WX12C10)
文摘Summary： This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system （RAAS） and clock genes in the kidney. The male Wistar rat models of 5/6 subtotal nephrectomy （STNx） were established. Animals were ran- domly divided into 4 groups： sham STNx group （control）, STNx group, morning benazepril group （MB） and evening benazepril group （EB）. Benazepril was intragastfically administered at a dose of 10 mg/kg/day at 07：00 and 19：00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light：dark cycle of 12：12 for 12 weeks. Systolic blood pressure （SBP）, 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity （RA）, angio- tensin Ⅱ （Ang Ⅱ ） and aldosterone （Aid） by radioimmunoassay （RIA） and the mRNA expression profile of clock genes （bmall, dbp and per2） by real-time PCR at 12 weeks. Our results showed that no signifi- cant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Aid and RA content of a day between the MB group and EB group. The expression peak of bmall mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects.
基金This work was supported by the National Natural Science Foundation of China(No.30170295),Medical Developmental Foundation of Soochow University(No.EEl 34031) and Young Teacher's Research Foundation of Soochow University(No.Q3134044).
