The Clock gene,a key molecule in circadian systems,is widely distributed in the animal kingdom. We isolated a 936-bp partial c DNA sequence of the C lock gene( Pva- clock) from the darkbarbel catfish P elteobagrus vac...The Clock gene,a key molecule in circadian systems,is widely distributed in the animal kingdom. We isolated a 936-bp partial c DNA sequence of the C lock gene( Pva- clock) from the darkbarbel catfish P elteobagrus vachelli that exhibited high identity with C lock genes of other species of fish and animals(65%–88%). The putative domains included a basic helix-loop-helix(b HLH) domain and two period-ARNT-single-minded(PAS) domains,which were also similar to those in other species of fish and animals. P va- Clock was primarily expressed in the brain,and was detected in all of the peripheral tissues sampled. Additionally,the pattern of P va- Clock expression over a 24-h period exhibited a circadian rhythm in the brain,liver and intestine,with the acrophase at zeitgeber time 21:35,23:00,and 23:23,respectively. Our results provide insight into the function of the molecular C lock of P. vachelli.展开更多
Biological rhythms controlled by the circadian clock are absent in embryonic stem cells (ESCs). However, they start to develop during the differentiation of pluripotent ESCs to downstream cells. Conversely, biologic...Biological rhythms controlled by the circadian clock are absent in embryonic stem cells (ESCs). However, they start to develop during the differentiation of pluripotent ESCs to downstream cells. Conversely, biological rhythms in adult somatic cells disappear when they are reprogrammed into induced pluripotent stem cells (iPSCs). These studies indicated that the development of biological rhythms in ESCs might be closely associated with the maintenance and differentiation of ESCs. The core circadian gene Clock is essential for regulation of biological rhythms. Its role in the development of biological rhythms of ESCs is totally unknown. Here, we used CRISPR/CAS9-mediated genetic editing techniques, to completely knock out the Clock expression in mouse ESCs. By AP, teratoma formation, quantitative real-time PCR and Immunofluorescent staining, we did not find any dif- ference between Clock knockout mESCs and wild type mESCs in morphology and pluripotent capability under the pluripotent state. In brief, these data indicated Clock did not influence the maintaining of pluripotent state. However, they exhibited decreased proliferation and increased apoptosis. Furthermore, the biological rhythms failed to develop in Clock knockout mESCs after spontaneous differentiation, which indicated that there was no compensational factor in most peripheral tissues as described in mice models before (DeBruyne et ah, 2007b). After spontaneous differentiation, loss of CLOCK protein due to Clock gene silencing induced spontaneous differentiation of mESCs, indicating an exit from the pluripotent state, or its differentiating ability. Our findings indicate that the core circadian gene Clock may be essential during normal mESCs differentiation by regulating mESCs proliferation, apoptosis and activity.展开更多
Due to regulation by circadian rhythm, the lactation of the mammary gland has rhythmicity. As one of prominent members of period protein family which regulates biological rhythms, PER2 plays an important role in devel...Due to regulation by circadian rhythm, the lactation of the mammary gland has rhythmicity. As one of prominent members of period protein family which regulates biological rhythms, PER2 plays an important role in developing the milk duct and maintaining the polarity and the morphology of the mammary epithelium; at the same time, it is also closely related with the metabolism of milk protein and milk fat. This paper summarized recent researches on PER2 gene and related researches on mammary gland development and metabolism to provide some information for the studies of the theory and technology on physiological functions of the mammary gland and milk quality control.展开更多
Current therapies for obesity and related complications have been shown to have limited benefits,including unsatisfactory weight loss and poor metabolic improvement.With recent developments in bariatric surgery,promis...Current therapies for obesity and related complications have been shown to have limited benefits,including unsatisfactory weight loss and poor metabolic improvement.With recent developments in bariatric surgery,promising advancements have been made in clinical and scientific research,particularly in the management of obesity and diabetes.Vertical sleeve gastrectomy(VSG)has become increasingly popular due to its safety,simplicity,展开更多
Early tuberization,a short period from stolon occurrence to tuber formation,is one of the major characteristics of a good early-maturing potato cultivar,while the regulatory mechanism of tuberization time(TT)is still ...Early tuberization,a short period from stolon occurrence to tuber formation,is one of the major characteristics of a good early-maturing potato cultivar,while the regulatory mechanism of tuberization time(TT)is still unclear.In this study,two tetraploid cultivars,Zhongshu 3(Z3)and Zhongshu 18(Z18),with short and long TT respectively,were examined to reveal regulatory genes related to TT using RNA sequencing of tissue samples taken during stolon occurrence,stolon swelling and tuber formation.Cluster analysis showed that the gene expression patterns at the stolon swelling and tuber formation stages were significantly different from those at stolon occurrence in both Z3 and Z18.Therefore,we screened the differentially expressed genes(DEGs)at stolon swelling and tuber formation and compared them to those at stolon occurrence.A total of 3085 DEGs were specifically identified and analyzed according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment,and DEGs involved in starch and sucrose metabolism,plant hormone signal transduction and plant circadian clock were significantly enriched.The circadian clock genes were significantly differentially expressed between Z3 and Z18,revealing an important role for the plant circadian pathway in regulating TT.Furthermore,three candidate genes,StGI,StPRR and StEFM involved in circadian regulation and significantly differentially expressed between Z3 and Z18,were discovered and confirmed by qRT-PCR.The results provide valuable information for understanding the regulatory mechanisms of potato TT and represent a step toward breeding early-maturing potato cultivars.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
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
The circadian clock is a fundamental endogenous mechanism of adaptation that coordinates the physiology and behavior of most organisms with diel variations in the external environment to maintain temporal homeostasis....The circadian clock is a fundamental endogenous mechanism of adaptation that coordinates the physiology and behavior of most organisms with diel variations in the external environment to maintain temporal homeostasis.Diatoms are the major primary producers in the ocean.However,little is known about the circadian clock in marine diatoms compared with other organisms.Here,we investigated circadian clock genes,their expression patterns,and responses to environmental stimuli such as light,nitrogen and phosphorus in two marine diatoms,Skeletonema costatum and Phaeodactylum tricornutum,using a combination of q RT-PCR and bioinformatic analysis.We identified 17 and 18 circadian clock genes in P.tricornutum and S.costatum,respectively.Despite significant evolutionary differences,these genes were similar to those of the higher plant Arabidopsis.We also established a molecular model for the marine diatom circadian clock comprising an input pathway,core oscillator,output pathway,and valve effector.Notably,the expression patterns of core clock genes(circadian clock associated 1(CCA1),late elongated hypocotyl(LHY)and timing of cab 1(TOC1))in both species differed from those of terrestrial plants.Furthermore,the expression of these genes was influenced by variations in ambient light,nitrogen and phosphorus availability.Although marine diatoms and higher plants share common circadian clock components,their clock genes have diverged throughout evolution,likely as a result of adapting to contrasting environments.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
Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic conditions.Its importance in cardiovascular diseases,particularly in cardiac ischem...Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic conditions.Its importance in cardiovascular diseases,particularly in cardiac ischemia,is because of its ability to alleviate cardiac dysfunction.The oxygen-responsive subunit,HIF1α,plays a crucial role in this process,as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival,angiogenesis,and metabolism.Furthermore,HIF1αexpression induced reperfusion in the ischemic skeletal muscle,and hypoxic skin wounds in diabetic animal models showed reduced HIF1αexpression.Increased expression of HIF1αhas been shown to reduce apoptosis and oxidative stress in cardiomyocytes during acute myocardial infarction.Genetic variations in HIF1αhave also been found to correlate with altered responses to ischemic cardiovascular disease.In addition,a link has been established between the circadian rhythm and hypoxic molecular signaling pathways,with HIF1αfunctioning as an oxygen sensor and circadian genes such as period circadian regulator 2 responding to changes in light.This editorial analyzes the relationship between HIF1αand the circadian rhythm and highlights its significance in myocardial adaptation to hypoxia.Understanding the changes in molecular signaling pathways associated with diseases,specifically cardiovascular diseases,provides the opportunity for innovative therapeutic interventions,especially in low-oxygen environments such as myocardial infarction.展开更多
基金Supported by the National Natural Science Foundation of China(No.31402305)the Educational Commission of Sichuan Province of China(No.14ZA0249)+1 种基金the Key Technologies R&D Program of Neijiang,Sichuan,China(No.12108)the College Students’ Scientific Research Project of Neijiang Normal University(Nos.13NSD-66,13NSD-77)
文摘The Clock gene,a key molecule in circadian systems,is widely distributed in the animal kingdom. We isolated a 936-bp partial c DNA sequence of the C lock gene( Pva- clock) from the darkbarbel catfish P elteobagrus vachelli that exhibited high identity with C lock genes of other species of fish and animals(65%–88%). The putative domains included a basic helix-loop-helix(b HLH) domain and two period-ARNT-single-minded(PAS) domains,which were also similar to those in other species of fish and animals. P va- Clock was primarily expressed in the brain,and was detected in all of the peripheral tissues sampled. Additionally,the pattern of P va- Clock expression over a 24-h period exhibited a circadian rhythm in the brain,liver and intestine,with the acrophase at zeitgeber time 21:35,23:00,and 23:23,respectively. Our results provide insight into the function of the molecular C lock of P. vachelli.
文摘Biological rhythms controlled by the circadian clock are absent in embryonic stem cells (ESCs). However, they start to develop during the differentiation of pluripotent ESCs to downstream cells. Conversely, biological rhythms in adult somatic cells disappear when they are reprogrammed into induced pluripotent stem cells (iPSCs). These studies indicated that the development of biological rhythms in ESCs might be closely associated with the maintenance and differentiation of ESCs. The core circadian gene Clock is essential for regulation of biological rhythms. Its role in the development of biological rhythms of ESCs is totally unknown. Here, we used CRISPR/CAS9-mediated genetic editing techniques, to completely knock out the Clock expression in mouse ESCs. By AP, teratoma formation, quantitative real-time PCR and Immunofluorescent staining, we did not find any dif- ference between Clock knockout mESCs and wild type mESCs in morphology and pluripotent capability under the pluripotent state. In brief, these data indicated Clock did not influence the maintaining of pluripotent state. However, they exhibited decreased proliferation and increased apoptosis. Furthermore, the biological rhythms failed to develop in Clock knockout mESCs after spontaneous differentiation, which indicated that there was no compensational factor in most peripheral tissues as described in mice models before (DeBruyne et ah, 2007b). After spontaneous differentiation, loss of CLOCK protein due to Clock gene silencing induced spontaneous differentiation of mESCs, indicating an exit from the pluripotent state, or its differentiating ability. Our findings indicate that the core circadian gene Clock may be essential during normal mESCs differentiation by regulating mESCs proliferation, apoptosis and activity.
基金supported by the Natural Science Foundation(BK20151312,BK20141270)2015 University Student Innovation Training Program(201511117037)of Jiangsu ProvincePriority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)P.R.China
文摘Due to regulation by circadian rhythm, the lactation of the mammary gland has rhythmicity. As one of prominent members of period protein family which regulates biological rhythms, PER2 plays an important role in developing the milk duct and maintaining the polarity and the morphology of the mammary epithelium; at the same time, it is also closely related with the metabolism of milk protein and milk fat. This paper summarized recent researches on PER2 gene and related researches on mammary gland development and metabolism to provide some information for the studies of the theory and technology on physiological functions of the mammary gland and milk quality control.
基金supported by the National Natural Science Foundation of China(81370938)Shanghai Municipal Commission of Health and Family Planning(XYQ2011002)+2 种基金Shanghai Science and Technology Committee(11PJ1402000)Shenkang Hospital Development Center(SHDC12012220)the ‘‘Strategic Priority Research Program” of the Chinese Academy of Science(XDB13030500)
文摘Current therapies for obesity and related complications have been shown to have limited benefits,including unsatisfactory weight loss and poor metabolic improvement.With recent developments in bariatric surgery,promising advancements have been made in clinical and scientific research,particularly in the management of obesity and diabetes.Vertical sleeve gastrectomy(VSG)has become increasingly popular due to its safety,simplicity,
基金This research was funded by the National Natural Science Foundation of China(Grant No.31771860)National Key R&D Program of China(Grant No.2017YFD0101905)China Agriculture Research System(CARS-09).
文摘Early tuberization,a short period from stolon occurrence to tuber formation,is one of the major characteristics of a good early-maturing potato cultivar,while the regulatory mechanism of tuberization time(TT)is still unclear.In this study,two tetraploid cultivars,Zhongshu 3(Z3)and Zhongshu 18(Z18),with short and long TT respectively,were examined to reveal regulatory genes related to TT using RNA sequencing of tissue samples taken during stolon occurrence,stolon swelling and tuber formation.Cluster analysis showed that the gene expression patterns at the stolon swelling and tuber formation stages were significantly different from those at stolon occurrence in both Z3 and Z18.Therefore,we screened the differentially expressed genes(DEGs)at stolon swelling and tuber formation and compared them to those at stolon occurrence.A total of 3085 DEGs were specifically identified and analyzed according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment,and DEGs involved in starch and sucrose metabolism,plant hormone signal transduction and plant circadian clock were significantly enriched.The circadian clock genes were significantly differentially expressed between Z3 and Z18,revealing an important role for the plant circadian pathway in regulating TT.Furthermore,three candidate genes,StGI,StPRR and StEFM involved in circadian regulation and significantly differentially expressed between Z3 and Z18,were discovered and confirmed by qRT-PCR.The results provide valuable information for understanding the regulatory mechanisms of potato TT and represent a step toward breeding early-maturing potato cultivars.
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.
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.
基金The National Natural Science Foundation of China under contract Nos 41425021 and 41706131the National Key Research and Development Program of China under contract No.2017YFC1404302the“Ten Thousand Talents Program”for Leading Talents in Science and Technological Innovation to Dazhi Wang。
文摘The circadian clock is a fundamental endogenous mechanism of adaptation that coordinates the physiology and behavior of most organisms with diel variations in the external environment to maintain temporal homeostasis.Diatoms are the major primary producers in the ocean.However,little is known about the circadian clock in marine diatoms compared with other organisms.Here,we investigated circadian clock genes,their expression patterns,and responses to environmental stimuli such as light,nitrogen and phosphorus in two marine diatoms,Skeletonema costatum and Phaeodactylum tricornutum,using a combination of q RT-PCR and bioinformatic analysis.We identified 17 and 18 circadian clock genes in P.tricornutum and S.costatum,respectively.Despite significant evolutionary differences,these genes were similar to those of the higher plant Arabidopsis.We also established a molecular model for the marine diatom circadian clock comprising an input pathway,core oscillator,output pathway,and valve effector.Notably,the expression patterns of core clock genes(circadian clock associated 1(CCA1),late elongated hypocotyl(LHY)and timing of cab 1(TOC1))in both species differed from those of terrestrial plants.Furthermore,the expression of these genes was influenced by variations in ambient light,nitrogen and phosphorus availability.Although marine diatoms and higher plants share common circadian clock components,their clock genes have diverged throughout evolution,likely as a result of adapting to contrasting environments.
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Supported by Croatian Ministry of Science and Education,Josip Juraj Strossmayer University of Osijek,Faculty of Dental Medicine and Health,Osijek,Croatia,No.IP7-FDMZ-2023West-Siberian Science and Education Center,Government of Tyumen District,Decree of 20.11.2020,No.928-rpMinistry of Science and Higher Education,No.FMEN 2022-0009.
文摘Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic conditions.Its importance in cardiovascular diseases,particularly in cardiac ischemia,is because of its ability to alleviate cardiac dysfunction.The oxygen-responsive subunit,HIF1α,plays a crucial role in this process,as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival,angiogenesis,and metabolism.Furthermore,HIF1αexpression induced reperfusion in the ischemic skeletal muscle,and hypoxic skin wounds in diabetic animal models showed reduced HIF1αexpression.Increased expression of HIF1αhas been shown to reduce apoptosis and oxidative stress in cardiomyocytes during acute myocardial infarction.Genetic variations in HIF1αhave also been found to correlate with altered responses to ischemic cardiovascular disease.In addition,a link has been established between the circadian rhythm and hypoxic molecular signaling pathways,with HIF1αfunctioning as an oxygen sensor and circadian genes such as period circadian regulator 2 responding to changes in light.This editorial analyzes the relationship between HIF1αand the circadian rhythm and highlights its significance in myocardial adaptation to hypoxia.Understanding the changes in molecular signaling pathways associated with diseases,specifically cardiovascular diseases,provides the opportunity for innovative therapeutic interventions,especially in low-oxygen environments such as myocardial infarction.