The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for th...The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for the development of the reproductive system,maintenance of reproductive function,and the overall health of males.The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes.Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis.We also examined the specific effects of these genes on the occurrence,development,and treatment of common male diseases,including late-onset hypogonadism,erectile dysfunction,male infertility,and prostate cancer.展开更多
This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression...This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression pattern in OSCC,and the expression levels of PERs in OSCC patients are correlated with a favorable prognosis.PERs impact the occurrence and development of OSCC through multiple pathways.In the regulation of cell proliferation,they can function not only through cell cycle regultion but also via metabolic pathways.For example,PER1 can interact with receptors for activated C kinase 1(RACK1)and phosphatidylinositol 3-kinase(PI3K)through its PAS domain to inhibit glycolysis and thereby reduce cell proliferation.Regarding the regulation of cell death,PERs mediate various types of cell death in OSCC cells,such as p53-dependent apoptosis,protein kinase B(AKT)/mammalian target of rapamycin(mTOR)dependent autophagy,or hypoxia-inducible factor l-alpha(HIF-1a)mediated ferroptosis.In regulating epithelia-mesenchymal transition(EMT),PERs can lead to the downregulation of EMT related genes,such as zinc finger E-box binding homeobox 1/2(ZEBI/2),twist family BHLH transcription factor 1/2(TWIST1/2),and Vimentin,thereby influencing the migration and invasion capabilities of OSCC cells.In tumor angiogenesis,PERs exert regulatory effects on related factors,such as methionyl aminopeptidase 2(MetAP2)and vascular endothelial growth factor(VEGF).In the tumor immune microenvironment,PERs can inhibit the inhibitor of kappa B kinase(IKK)/nuclear factor kappa B(NF-kB)pathway and programmed cell death ligand 1(PD-L1)expression,thereby enhancing the cytotoxic effect of CD8+T cells on OSCC cells.In-depth studies focusing on elucidating the precise regulatory mechanisms of PERs can facilitate the development of therapeutic strategies targeting PERs,including restoration of PERs expression/activity,targeting PERs-regulated pathways,combination therapies,and chronotherapy.These furnish a theoretical foundation for formulating individualized treatment plans to achieve precise treatment for patients with OSCC.展开更多
The circadian clock is a highly conserved timekeeping system in organisms,which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression.Substantial clinical and experimenta...The circadian clock is a highly conserved timekeeping system in organisms,which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression.Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies.Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues,primarily manifested as a dysfunction of core clock components(particularly circadian locomotor output cycles kaput(CLOCK)and brain and muscle ARNT-like 1(BMAL1))and the widespread dysregulation of their downstream target genes.Notably,CLOCK demonstrates non-canonical oncogenic functions,including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways.This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1,encompassing multidimensional effects such as cell cycle control,DNA damage response,metabolic reprogramming,and tumor microenvironment(TME)remodeling.Regarding the therapeutic strategies,we focus on cutting-edge approaches such as chrononutritional interventions,chronopharmacological modulation,and treatment regimen optimization,along with a discussion of future perspectives.The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology,particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.展开更多
The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given th...The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.展开更多
Major depressive disorder(MDD)affects people all over the world,and yet,its etiology is complex and remains incompletely understood.In this review,we aim to assess recent advances in understanding depression and its r...Major depressive disorder(MDD)affects people all over the world,and yet,its etiology is complex and remains incompletely understood.In this review,we aim to assess recent advances in understanding depression and its regulation,as well as its interaction with circadian rhythms.Circadian rhythms are internalized representations of the periodic daily light and dark cycles.Accumulating evidence has shown that MDD and the related mental disorders are associated with disrupted circadian rhythms.In particular,depression has often been linked to abnormalities in circadian rhythms because dysregulation of the circadian system increases susceptibility to MDD.The fact that several rhythms are disrupted in depressed patients suggests that these disruptions are not restricted to any one rhythm but rather involve the molecular circadian clock core machinery.The sleep-wake cycle is one rhythm that is often disrupted in depression,which often leads to disturbances in other rhythms.The circadian disruptions manifested in depressed patients and the effectiveness and fast action of chronobiologically based treatments highlight the circadian system as a key therapeutic target in the treatment of depression.This review assesses the evidence on rising depression rates and examines their contributing factors,including circadian misalignment.We discuss key hypotheses underlying depression pathogenesis,potential etiology,and relevant animal models,and underscore potential mechanisms driving depression's growing burden and how understanding these factors is critical for improving prevention and treatment strategies.展开更多
Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals an...Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.展开更多
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
Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response an...Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response and exacerbating glycolysis in multiple tissues.However,the redox induction mechanism of lactate in mammary gland has not been understood yet.Herein,we describe a lactate-responsive HIF1α/circadian control mechanism in oxidative stress in the mammary glands of dairy cows.Results The in vivo study showed that dairy cows with high lactate concentrations are associated with reduced milk yield and more ROS accumulation in mammary gland.Western blot results in MAC-T cells showed positive correlation between lactate concentrations,expression of HIF1αand oxidative stress indicators,but not circadian core components.To test how lactate-mediated HIF1αdysfunction leads to cell protection process,we investigated altered expression of circadian core related genes following HIF1αstabilization.We found that stabilized HIF1αby lactate inhibited stimulated expression of circadian core components due to the similarity of HRE and E-box transcription elements.Furthermore,we found that lactate treatment strengthened the binding of HIF1αwith BMAL1,HMOX1 and FOXO3 in MAC-T cells.Moreover,HIF1αknockdown altered expression of circadian rhythm related genes and reduced oxidative stress state.Conclusion In summary,our study highlights the central role of competitive transcriptional element occupancy in lactate-mediated oxidative stress of mammary gland,which is caused by HIF1αstabilization and circadian rhythm dysfunction.Our findings introduce a novel nutritional strategy with potential applications in dairy farming for optimizing milk production and maintaining mammary gland health.展开更多
The circadian system of mammals is composed of a hierarchical network of oscillators,including a core clock and peripheral clocks.The core clock receives an external photic signal and transmits it to the peripheral cl...The circadian system of mammals is composed of a hierarchical network of oscillators,including a core clock and peripheral clocks.The core clock receives an external photic signal and transmits it to the peripheral clocks,which,in turn,feed back to the core clock.Aging affects various functions of organisms including the circadian system.Entrainment displays the adaptability of the circadian system to changes in the external environment.However,there is currently no systematic study on the effects of aging on the entrainment capability.To explore the influencing mechanism,we develop a mathematical model of two populations of Goodwin oscillators,which represent the core clock and peripheral clocks.Based on numerical simulations,we conduct a detailed study on the impact of three aging-related factors on the entrainment capability represented by the entrainment range,entrainment time,and entrainment phase.The results indicate that the decrease in the sensitivity of suprachiasmatic nucleus(SCN)to light and the coupling strength from the SCN to the peripheral clocks due to aging increase the phase difference between the core and peripheral clocks,narrow the entrainment range,and prolong the entrainment time.A reduction in the coupling strength within the SCN has little effect on the three aspects mentioned above but increases the entrainment phase.Overall,aging reduces the circadian system's adaptability to the external environment,and the increased entrainment phase may lead to corresponding sleep problems.We also show that modulating the internal coupling strength in the peripheral clocks can mitigate aging effects;this provides an idea for using peripheral clocks to adjust the core clock,while also revealing new insights into the interaction between aging and the elasticity of the circadian system.This mechanism provides theoretical support for treating or alleviating circadian system disorders or sleep problems caused by aging.展开更多
The plant circadian clock temporally drives gene expression throughout the day and coordinates various physiological processes with diurnal environmental changes. It is essential for conferring plant fitness and compe...The plant circadian clock temporally drives gene expression throughout the day and coordinates various physiological processes with diurnal environmental changes. It is essential for conferring plant fitness and competitive advantages to survive and thrive under natural conditions through the circadian control of gene transcription. Chinese cabbage(Brassica rapa ssp. pekinensis) is an economically important vegetable crop worldwide, although there is little information concerning its circadian clock system. Here we found that gene expression patterns are affected bycircadian oscillators at both the transcriptional and post-transcriptional levels in Chinese cabbage. Time-course RNA-seq analyses were conducted on two short-period lines(SPcc-1 and SPcc-2) and two long-period lines(LPcc-1 and LPcc-2) under constant light. The results showed that 32.7–50.5% of the genes were regulated bythe circadian oscillator and the expression peaks of cycling genes appeared earlier in short-period lines than long-period lines. In addition, approximately 250 splicing events exhibited circadian regulation, with intron retention(IR) accounting for a large proportion. Rhythmically spliced genes included the clock genes LATE ELONGATEDHYPOCOTYL(BrLHY), REVEILLE 2(BrRVE2) and EARLY FLOWERING 3(BrELF3). We also found that thecircadian oscillator could notably influence the diurnal expression patterns of genes that are associated with glucose metabolism via photosynthesis, the Calvin cycle and the tricarboxylic acid(TCA) cycle at both the transcriptional andpost-transcriptional levels. The collective results of this study demonstrate that circadian-regulated physiological processes contribute to Chinese cabbage growth and development.展开更多
During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many...During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many edible plants,can ameliorate obesity by activating adipose tissue browning,but its effect on circadian clock in this process remains poorly understood.Here we found that dietary LU improved circadian misalignment of energy expenditure in high-fat diet(HFD)-fed wild-type(WT)mice.Moreover,dietary LU efficiently elevated uncoupling protein 1 levels in adipose tissue during the dark period,which was similar to the LU-increased hepatic PER2 expressions.Hepatic peroxisome proliferators-activated receptorsα(PPARα)/recombinant retinoid X receptorα(RXRα)/fibroblast growth factor 21(FGF21)pathway was rhythmically elevated by dietary LU in HFD-fed WT mice,whereas the promotion was inhibited in Per2^(-/-)mice.Meanwhile,Per2 deletion abolished the effects of dietary LU on adipose tissue browning in HFD-fed mice.Further,LU treatment directly activated PPARα/RXRα/FGF21 signaling in primary cultured hepatocytes from WT mice rather than Per2^(-/-)mice.Taken together,the deletion of the core clock component Per2 impedes LUinduced adipose tissue browning through weakening PPARα/RXRα/FGF21 pathway in mice,providing a new insight into the interplay of energy metabolism and circadian clock for the anti-obesity activity of LU.展开更多
Objective:Circadian rhythm disruption(CRD)is a risk factor that correlates with poor prognosis across multiple tumor types,including hepatocellular carcinoma(HCC).However,its mechanism remains unclear.This study aimed...Objective:Circadian rhythm disruption(CRD)is a risk factor that correlates with poor prognosis across multiple tumor types,including hepatocellular carcinoma(HCC).However,its mechanism remains unclear.This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity.Methods:To quantify CRD,the HCC CRD score(HCCcrds)was developed.Using machine learning algorithms,we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort(n=369),and the robustness of this method was validated.Furthermore,we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes.Results:We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis.The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis,higher pathological grade,and advanced clinical stages,while the CRD-related subtype with low HCCcrds had better clinical outcomes.We also identified novel biomarkers for each subtype,such as nicotinamide nmethyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1.Conclusion:We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers.Within these groups greater HCCcrds was associated with worse prognosis.This approach has the potential to improve prediction of an individual’s prognosis,guide precision treatments,and assist clinical decision making for HCC patients.展开更多
Objective:To analyze the characteristics of ambulatory blood pressure in elderly patients with hypertension and find out the risk factors of abnormal circadian rhythm.Methods:According to the circadian rhythm of patie...Objective:To analyze the characteristics of ambulatory blood pressure in elderly patients with hypertension and find out the risk factors of abnormal circadian rhythm.Methods:According to the circadian rhythm of patients'blood pressure,they were divided into Group A,Group B and Group C,and all the data of hypertension patients in this study were collected,including age,gender,BMI,smoking,drinking,basic diseases(diabetes,cerebrovascular disease,hyperlipidemia,etc.),fasting blood glucose,ambulatory blood pressure(24-hour mean systolic pressure,24-hour mean diastolic pressure,daytime mean systolic pressure and daytime mean diastolic pressure).Results:There were significant differences in mean systolic blood pressure and mean diastolic blood pressure at night among Group A,Group B and Group C(P<0.05).Age,hyperlipidemia and fasting blood glucose were risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium was a protective factor for circadian rhythm abnormality(P<0.05).Conclusion:Age,hyperlipidemia and fasting blood glucose are risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium is a protective factor for circadian rhythm abnormality(P<0.05).展开更多
Objective:To analyze the characteristics of ambulatory blood pressure in elderly patients with hypertension and find out the risk factors of abnormal circadian rhythm.Methods:According to the circadian rhythm of patie...Objective:To analyze the characteristics of ambulatory blood pressure in elderly patients with hypertension and find out the risk factors of abnormal circadian rhythm.Methods:According to the circadian rhythm of patients’blood pressure,they were divided into group A,group B,and group C,and all the data of hypertension patients in this study were collected,including age,gender,BMI,smoking,drinking,basic diseases(diabetes,cerebrovascular disease,hyperlipidemia,etc.),fasting blood glucose,ambulatory blood pressure(24-hour mean systolic pressure,24-hour mean diastolic pressure,daytime mean systolic pressure and daytime mean diastolic pressure).Results:There were significant differences in mean systolic blood pressure and mean diastolic blood pressure at night among group A,group B and group C(P<0.05).Age,hyperlipidemia and fasting blood glucose were risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium was a protective factor for circadian rhythm abnormality(P<0.05).Conclusion:Age,hyperlipidemia and fasting blood glucose are risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium is a protective factor for circadian rhythm abnormality(P<0.05).展开更多
In mammals,the timing of physiological,biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms.To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus ...In mammals,the timing of physiological,biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms.To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm,environmental zeitgebers are used by the circadian system.This is done primarily by signals from the retina via the retinohypothalamic tract,but other cues like exercise,feeding,temperature,anxiety,and social events have also been shown to act as non-photic zeitgebers.The recently identified myokine irisin is proposed to serve as an entraining non-photic signal of exercise.Irisin is a product of cleavage and modification from its precursor membrane fibronectin typeⅢdomain-containing protein 5(FNDC5)in response to exercise.Apart from well-known peripheral effects,such as inducing the"browning"of white adipocytes,irisin can penetrate the blood-brain barrier and display the effects on the brain.Experimental data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain functions.In several brain areas,irisin induces the production of brain-derived neurotrophic factor(BDNF).In the master clock,a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is suggested.However,the brain receptor for irisin remains unknown.In the current review,the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.展开更多
This review delved into the intricate relationship between circadian clocks and physiological processes,emphasizing their critical role in maintaining homeo-stasis.Orchestrated by interlocked clock genes,the circadian...This review delved into the intricate relationship between circadian clocks and physiological processes,emphasizing their critical role in maintaining homeo-stasis.Orchestrated by interlocked clock genes,the circadian timekeeping system regulates fundamental processes like the sleep-wake cycle,energy metabolism,immune function,and cell proliferation.The central oscillator in the hypothalamic suprachiasmatic nucleus synchronizes with light-dark cycles,while peripheral tissue clocks are influenced by cues such as feeding times.Circadian disruption,linked to modern lifestyle factors like night shift work,correlates with adverse health outcomes,including metabolic syndrome,cardiovascular diseases,infec-tions,and cancer.We explored the molecular mechanisms of circadian clock genes and their impact on metabolic disorders and cancer pathogenesis.Specific associ-ations between circadian disruption and endocrine tumors,spanning breast,ovarian,testicular,prostate,thyroid,pituitary,and adrenal gland cancers,are highlighted.Shift work is associated with increased breast cancer risk,with PER genes influencing tumor progression and drug resistance.CLOCK gene expression correlates with cisplatin resistance in ovarian cancer,while factors like aging and intermittent fasting affect prostate cancer.Our review underscored the intricate interplay between circadian rhythms and cancer,involving the regulation of the cell cycle,DNA repair,metabolism,immune function,and the tumor microenvir-onment.We advocated for integrating biological timing into clinical consider-ations for personalized healthcare,proposing that understanding these connec-tions could lead to novel therapeutic approaches.Evidence supports circadian rhythm-focused therapies,particularly chronotherapy,for treating endocrine tumors.Our review called for further research to uncover detailed connections between circadian clocks and cancer,providing essential insights for targeted treatments.We emphasized the importance of public health interventions to mitigate lifestyle-related circadian disruptions and underscored the critical role of circadian rhythms in disease mechanisms and therapeutic interventions.展开更多
Gut microbiome is indispensable for maintaining normal brain function.Specifically,gut microbiota plays a causal role in sleep deprivation(SD)-induced cognitive impairment.In this study,neurobehavioral effects of the ...Gut microbiome is indispensable for maintaining normal brain function.Specifically,gut microbiota plays a causal role in sleep deprivation(SD)-induced cognitive impairment.In this study,neurobehavioral effects of the Bifidobacterium breve strain(CCFM1025)were assessed in sleep-deprived mice.CCFM1025 improved the body weight and food and water intake of the mice.It also alleviated SD-induced cognitive behavioural abnormalities(in the novel object recognition test),but did not show beneficial effects on mood-and spatial memory-related behaviours.CCFM1025 significantly altered the gut microbial composition and genome function.Key microbial metabolites that may regulate sleep function were also identified,such as isovaleric acid andγ-aminobutyric acid in the gut and purine metabolites in the serum.Those metabolites may participate in gutbrain communication by acting on the striatal melatonin system,for example to increase melatonin levels,and by regulating the expression of circadian clock genes such as those encoding the adenosine A2A receptor and period circadian regulator 1.Collectively,administration of probiotics alleviated cognitive impairment and circadian rhythm disturbance induced by SD via modulation of gut microbiome and its metabolites.These findings may help guide the treatment of insomnia or other sleep disorders via dietary strategies.展开更多
Precise timing of flowering in plants is critical for their growth and reproductive processes.One factor controlling flowering time is the cycle of light and darkness within a day,known as the photoperiod.Plants are c...Precise timing of flowering in plants is critical for their growth and reproductive processes.One factor controlling flowering time is the cycle of light and darkness within a day,known as the photoperiod.Plants are classified into long-day,short-day,and day-neutral plants based on light requirements for floral initiation.Although the molecular mechanisms that govern this differentiation remain incompletely understood,studies have consistently shown that the circadian clock plays a central role in regulating photoperiod response across diverse plant species.However,there is a scarcity of reviews describing the regulatory network linking the circadian clock with photoperiodic flowering.This review summarizes that regulatory network,focusing on the distinct roles of clock genes in long-day and short-day plants.We also discuss the strategies of clock gene mutations contributing to geographic variation in longday and short-day crops.展开更多
Aging and circadian rhythms have been connected for decades,but their molecular interaction has remained unknown,especially for cancers.In this situation,we summarized the current research actuality and problems in th...Aging and circadian rhythms have been connected for decades,but their molecular interaction has remained unknown,especially for cancers.In this situation,we summarized the current research actuality and problems in this field using the bibliometric analysis.Publications in the PubMed and Web of Science databases were retrieved.Overall,there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer.Researchers from USA,Germany,Italy,China and England have greater studies than others.Top three publication institutions are University of California System,UDICE-French Research Universities and University of Texas System.Current research hotspots include oxidative stress,breast cancer,melatonin,cell cycle,calorie restriction,prostate cancer and NF-κB.In conclusion,results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer.These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.展开更多
In order to explore the impact of circadian disturbance on erectile function,we randomly divided 24 adult male rats into groups of control(light on at 8:00 a.m.and off at 8:00 p.m.),dark/dark(DD;constant dark),light/l...In order to explore the impact of circadian disturbance on erectile function,we randomly divided 24 adult male rats into groups of control(light on at 8:00 a.m.and off at 8:00 p.m.),dark/dark(DD;constant dark),light/light(LL;constant light),and shift dark/light(DL;light off at 8:00 a.m.and on at 8:0o p.m.).Four weeks later,erectile function was measured and corpora cavernosa were harvested for analysis.The maximum intracavernous pressure(mlcP)and mCP/mean arterial pressure(MAP)ratio in the DD,LL,and DL groups were significantly lower than that in the control group.The LL and DL groups showed significantly attenuated endothelial nitric oxide synthase(eNOS),while DD,LL,and DL showed reduced neuronal nitric oxide synthase(nNOS)at both mRNA and protein levels.The production of nitric oxide(NO)and cyclic guanosinemonophosphate(cGMP)was inhibited by altered light/dark cycles to varying degrees.Circadian disturbance impaired endothelial function and contributed to erectile dysfunction.For the core circadian elements,mRNA expression of circadian locomotor output cycles kaput(Clock)and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1(Bmal1)was elevated in the DL group,but their protein expression was not significantly changed.DD,LL,and DL increased period 1(Per1)and Per3 levels,while LL and DL increased PER1 levels.No significant difference was found for Per2levels,and PER2 and PER3 concentrations were not significantly changed.Moreover,LL and DL significantly increased cryptochrome-1(CRY1)and CRY2 at both mRNA and protein levels.The altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial function.Meanwhile,the core circadian elements were detected in the corpora cavernosa,but these were disrupted.However,which circadian element regulates erectile function and how it works need further analysis.展开更多
基金supported by grants from the National Natural Science Foundation of China(N0.82474525 and No.82074444)the Hunan Provincial Natural Outstanding Young People Science Foundation(2023JJ10032)the Hunan Province Health and High-Level Talent Medical Academic Leader Training Plan(20240304051).
文摘The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for the development of the reproductive system,maintenance of reproductive function,and the overall health of males.The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes.Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis.We also examined the specific effects of these genes on the occurrence,development,and treatment of common male diseases,including late-onset hypogonadism,erectile dysfunction,male infertility,and prostate cancer.
基金supported by the following funding:National Natural Science Foundations of China(82002888,82272899 and 82370974)Sichuan Science and Technology Program(2022YFS0207 and 2023YFS0127)+1 种基金Scientific Research Foundation,WestChinaHospital of Stomatology SichuanUniversity(RCDWJS2021-8)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-004).
文摘This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression pattern in OSCC,and the expression levels of PERs in OSCC patients are correlated with a favorable prognosis.PERs impact the occurrence and development of OSCC through multiple pathways.In the regulation of cell proliferation,they can function not only through cell cycle regultion but also via metabolic pathways.For example,PER1 can interact with receptors for activated C kinase 1(RACK1)and phosphatidylinositol 3-kinase(PI3K)through its PAS domain to inhibit glycolysis and thereby reduce cell proliferation.Regarding the regulation of cell death,PERs mediate various types of cell death in OSCC cells,such as p53-dependent apoptosis,protein kinase B(AKT)/mammalian target of rapamycin(mTOR)dependent autophagy,or hypoxia-inducible factor l-alpha(HIF-1a)mediated ferroptosis.In regulating epithelia-mesenchymal transition(EMT),PERs can lead to the downregulation of EMT related genes,such as zinc finger E-box binding homeobox 1/2(ZEBI/2),twist family BHLH transcription factor 1/2(TWIST1/2),and Vimentin,thereby influencing the migration and invasion capabilities of OSCC cells.In tumor angiogenesis,PERs exert regulatory effects on related factors,such as methionyl aminopeptidase 2(MetAP2)and vascular endothelial growth factor(VEGF).In the tumor immune microenvironment,PERs can inhibit the inhibitor of kappa B kinase(IKK)/nuclear factor kappa B(NF-kB)pathway and programmed cell death ligand 1(PD-L1)expression,thereby enhancing the cytotoxic effect of CD8+T cells on OSCC cells.In-depth studies focusing on elucidating the precise regulatory mechanisms of PERs can facilitate the development of therapeutic strategies targeting PERs,including restoration of PERs expression/activity,targeting PERs-regulated pathways,combination therapies,and chronotherapy.These furnish a theoretical foundation for formulating individualized treatment plans to achieve precise treatment for patients with OSCC.
基金supported by the Ministry of Science and Technology of the People’s Republic of China(Nos.2020YFA0803300 and 2021YFA0805600)the National Natural Science Foundation of China(Nos.92157113,82072630,82173114,82072903,82272872,82002811,82188102,and 82030074)+2 种基金the Zhejiang Natural Science Foundation Key Project(Nos.LD22H160002 and LD21H160003)the Zhejiang Natural Science Foundation Discovery Project(No.LQ22H160023)the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2019R01001),China.
文摘The circadian clock is a highly conserved timekeeping system in organisms,which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression.Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies.Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues,primarily manifested as a dysfunction of core clock components(particularly circadian locomotor output cycles kaput(CLOCK)and brain and muscle ARNT-like 1(BMAL1))and the widespread dysregulation of their downstream target genes.Notably,CLOCK demonstrates non-canonical oncogenic functions,including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways.This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1,encompassing multidimensional effects such as cell cycle control,DNA damage response,metabolic reprogramming,and tumor microenvironment(TME)remodeling.Regarding the therapeutic strategies,we focus on cutting-edge approaches such as chrononutritional interventions,chronopharmacological modulation,and treatment regimen optimization,along with a discussion of future perspectives.The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology,particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.
基金supported by a grant from the French Society of Sleep Research and Medicine(to LS)The China Scholarship Council(to HL)The CNRS,INSERM,Claude Bernard University Lyon1(to LS)。
文摘The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.
基金supported by the National Natural Science Foundation of China(No.81701347,31961133026,81570171,31871187,and 81070455)the National Key R&D Program of China(No.2019YFA0802400)the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions。
文摘Major depressive disorder(MDD)affects people all over the world,and yet,its etiology is complex and remains incompletely understood.In this review,we aim to assess recent advances in understanding depression and its regulation,as well as its interaction with circadian rhythms.Circadian rhythms are internalized representations of the periodic daily light and dark cycles.Accumulating evidence has shown that MDD and the related mental disorders are associated with disrupted circadian rhythms.In particular,depression has often been linked to abnormalities in circadian rhythms because dysregulation of the circadian system increases susceptibility to MDD.The fact that several rhythms are disrupted in depressed patients suggests that these disruptions are not restricted to any one rhythm but rather involve the molecular circadian clock core machinery.The sleep-wake cycle is one rhythm that is often disrupted in depression,which often leads to disturbances in other rhythms.The circadian disruptions manifested in depressed patients and the effectiveness and fast action of chronobiologically based treatments highlight the circadian system as a key therapeutic target in the treatment of depression.This review assesses the evidence on rising depression rates and examines their contributing factors,including circadian misalignment.We discuss key hypotheses underlying depression pathogenesis,potential etiology,and relevant animal models,and underscore potential mechanisms driving depression's growing burden and how understanding these factors is critical for improving prevention and treatment strategies.
基金Supported by American Diabetes AssociationAmerican Heart Association+3 种基金NIH NIEHSNIH NIANIH NINDSand NIH ARRA.
文摘Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.
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.
基金supported by National Nature Science Foundation of China(32102552 and 32172741).
文摘Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response and exacerbating glycolysis in multiple tissues.However,the redox induction mechanism of lactate in mammary gland has not been understood yet.Herein,we describe a lactate-responsive HIF1α/circadian control mechanism in oxidative stress in the mammary glands of dairy cows.Results The in vivo study showed that dairy cows with high lactate concentrations are associated with reduced milk yield and more ROS accumulation in mammary gland.Western blot results in MAC-T cells showed positive correlation between lactate concentrations,expression of HIF1αand oxidative stress indicators,but not circadian core components.To test how lactate-mediated HIF1αdysfunction leads to cell protection process,we investigated altered expression of circadian core related genes following HIF1αstabilization.We found that stabilized HIF1αby lactate inhibited stimulated expression of circadian core components due to the similarity of HRE and E-box transcription elements.Furthermore,we found that lactate treatment strengthened the binding of HIF1αwith BMAL1,HMOX1 and FOXO3 in MAC-T cells.Moreover,HIF1αknockdown altered expression of circadian rhythm related genes and reduced oxidative stress state.Conclusion In summary,our study highlights the central role of competitive transcriptional element occupancy in lactate-mediated oxidative stress of mammary gland,which is caused by HIF1αstabilization and circadian rhythm dysfunction.Our findings introduce a novel nutritional strategy with potential applications in dairy farming for optimizing milk production and maintaining mammary gland health.
基金Project supported by the graduate training funds of Shanghai Ocean University in China。
文摘The circadian system of mammals is composed of a hierarchical network of oscillators,including a core clock and peripheral clocks.The core clock receives an external photic signal and transmits it to the peripheral clocks,which,in turn,feed back to the core clock.Aging affects various functions of organisms including the circadian system.Entrainment displays the adaptability of the circadian system to changes in the external environment.However,there is currently no systematic study on the effects of aging on the entrainment capability.To explore the influencing mechanism,we develop a mathematical model of two populations of Goodwin oscillators,which represent the core clock and peripheral clocks.Based on numerical simulations,we conduct a detailed study on the impact of three aging-related factors on the entrainment capability represented by the entrainment range,entrainment time,and entrainment phase.The results indicate that the decrease in the sensitivity of suprachiasmatic nucleus(SCN)to light and the coupling strength from the SCN to the peripheral clocks due to aging increase the phase difference between the core and peripheral clocks,narrow the entrainment range,and prolong the entrainment time.A reduction in the coupling strength within the SCN has little effect on the three aspects mentioned above but increases the entrainment phase.Overall,aging reduces the circadian system's adaptability to the external environment,and the increased entrainment phase may lead to corresponding sleep problems.We also show that modulating the internal coupling strength in the peripheral clocks can mitigate aging effects;this provides an idea for using peripheral clocks to adjust the core clock,while also revealing new insights into the interaction between aging and the elasticity of the circadian system.This mechanism provides theoretical support for treating or alleviating circadian system disorders or sleep problems caused by aging.
基金supported by the Science and Technology Program of Hebei Province, China (236Z2903G)the Innovative Research Group Project of Hebei Natural Science Foundation, China (C2024204246)+1 种基金the Hebei International Joint Research Center of Vegetable Functional Genomicsthe International Joint R&D Center of Hebei Province in Modern Agricultural Biotechnology for supporting this work。
文摘The plant circadian clock temporally drives gene expression throughout the day and coordinates various physiological processes with diurnal environmental changes. It is essential for conferring plant fitness and competitive advantages to survive and thrive under natural conditions through the circadian control of gene transcription. Chinese cabbage(Brassica rapa ssp. pekinensis) is an economically important vegetable crop worldwide, although there is little information concerning its circadian clock system. Here we found that gene expression patterns are affected bycircadian oscillators at both the transcriptional and post-transcriptional levels in Chinese cabbage. Time-course RNA-seq analyses were conducted on two short-period lines(SPcc-1 and SPcc-2) and two long-period lines(LPcc-1 and LPcc-2) under constant light. The results showed that 32.7–50.5% of the genes were regulated bythe circadian oscillator and the expression peaks of cycling genes appeared earlier in short-period lines than long-period lines. In addition, approximately 250 splicing events exhibited circadian regulation, with intron retention(IR) accounting for a large proportion. Rhythmically spliced genes included the clock genes LATE ELONGATEDHYPOCOTYL(BrLHY), REVEILLE 2(BrRVE2) and EARLY FLOWERING 3(BrELF3). We also found that thecircadian oscillator could notably influence the diurnal expression patterns of genes that are associated with glucose metabolism via photosynthesis, the Calvin cycle and the tricarboxylic acid(TCA) cycle at both the transcriptional andpost-transcriptional levels. The collective results of this study demonstrate that circadian-regulated physiological processes contribute to Chinese cabbage growth and development.
文摘During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many edible plants,can ameliorate obesity by activating adipose tissue browning,but its effect on circadian clock in this process remains poorly understood.Here we found that dietary LU improved circadian misalignment of energy expenditure in high-fat diet(HFD)-fed wild-type(WT)mice.Moreover,dietary LU efficiently elevated uncoupling protein 1 levels in adipose tissue during the dark period,which was similar to the LU-increased hepatic PER2 expressions.Hepatic peroxisome proliferators-activated receptorsα(PPARα)/recombinant retinoid X receptorα(RXRα)/fibroblast growth factor 21(FGF21)pathway was rhythmically elevated by dietary LU in HFD-fed WT mice,whereas the promotion was inhibited in Per2^(-/-)mice.Meanwhile,Per2 deletion abolished the effects of dietary LU on adipose tissue browning in HFD-fed mice.Further,LU treatment directly activated PPARα/RXRα/FGF21 signaling in primary cultured hepatocytes from WT mice rather than Per2^(-/-)mice.Taken together,the deletion of the core clock component Per2 impedes LUinduced adipose tissue browning through weakening PPARα/RXRα/FGF21 pathway in mice,providing a new insight into the interplay of energy metabolism and circadian clock for the anti-obesity activity of LU.
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(grant number:242300421283)+1 种基金Henan Province Science and Technology Research and Development(grant number:242102311176)Henan Province medical science and technology research project(grant number:SBGJ202403038)。
文摘Objective:Circadian rhythm disruption(CRD)is a risk factor that correlates with poor prognosis across multiple tumor types,including hepatocellular carcinoma(HCC).However,its mechanism remains unclear.This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity.Methods:To quantify CRD,the HCC CRD score(HCCcrds)was developed.Using machine learning algorithms,we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort(n=369),and the robustness of this method was validated.Furthermore,we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes.Results:We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis.The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis,higher pathological grade,and advanced clinical stages,while the CRD-related subtype with low HCCcrds had better clinical outcomes.We also identified novel biomarkers for each subtype,such as nicotinamide nmethyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1.Conclusion:We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers.Within these groups greater HCCcrds was associated with worse prognosis.This approach has the potential to improve prediction of an individual’s prognosis,guide precision treatments,and assist clinical decision making for HCC patients.
文摘Objective:To analyze the characteristics of ambulatory blood pressure in elderly patients with hypertension and find out the risk factors of abnormal circadian rhythm.Methods:According to the circadian rhythm of patients'blood pressure,they were divided into Group A,Group B and Group C,and all the data of hypertension patients in this study were collected,including age,gender,BMI,smoking,drinking,basic diseases(diabetes,cerebrovascular disease,hyperlipidemia,etc.),fasting blood glucose,ambulatory blood pressure(24-hour mean systolic pressure,24-hour mean diastolic pressure,daytime mean systolic pressure and daytime mean diastolic pressure).Results:There were significant differences in mean systolic blood pressure and mean diastolic blood pressure at night among Group A,Group B and Group C(P<0.05).Age,hyperlipidemia and fasting blood glucose were risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium was a protective factor for circadian rhythm abnormality(P<0.05).Conclusion:Age,hyperlipidemia and fasting blood glucose are risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium is a protective factor for circadian rhythm abnormality(P<0.05).
文摘Objective:To analyze the characteristics of ambulatory blood pressure in elderly patients with hypertension and find out the risk factors of abnormal circadian rhythm.Methods:According to the circadian rhythm of patients’blood pressure,they were divided into group A,group B,and group C,and all the data of hypertension patients in this study were collected,including age,gender,BMI,smoking,drinking,basic diseases(diabetes,cerebrovascular disease,hyperlipidemia,etc.),fasting blood glucose,ambulatory blood pressure(24-hour mean systolic pressure,24-hour mean diastolic pressure,daytime mean systolic pressure and daytime mean diastolic pressure).Results:There were significant differences in mean systolic blood pressure and mean diastolic blood pressure at night among group A,group B and group C(P<0.05).Age,hyperlipidemia and fasting blood glucose were risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium was a protective factor for circadian rhythm abnormality(P<0.05).Conclusion:Age,hyperlipidemia and fasting blood glucose are risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium is a protective factor for circadian rhythm abnormality(P<0.05).
基金supported by the Russian Science Foundation(Grant No.23-25-00152).
文摘In mammals,the timing of physiological,biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms.To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm,environmental zeitgebers are used by the circadian system.This is done primarily by signals from the retina via the retinohypothalamic tract,but other cues like exercise,feeding,temperature,anxiety,and social events have also been shown to act as non-photic zeitgebers.The recently identified myokine irisin is proposed to serve as an entraining non-photic signal of exercise.Irisin is a product of cleavage and modification from its precursor membrane fibronectin typeⅢdomain-containing protein 5(FNDC5)in response to exercise.Apart from well-known peripheral effects,such as inducing the"browning"of white adipocytes,irisin can penetrate the blood-brain barrier and display the effects on the brain.Experimental data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain functions.In several brain areas,irisin induces the production of brain-derived neurotrophic factor(BDNF).In the master clock,a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is suggested.However,the brain receptor for irisin remains unknown.In the current review,the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.
文摘This review delved into the intricate relationship between circadian clocks and physiological processes,emphasizing their critical role in maintaining homeo-stasis.Orchestrated by interlocked clock genes,the circadian timekeeping system regulates fundamental processes like the sleep-wake cycle,energy metabolism,immune function,and cell proliferation.The central oscillator in the hypothalamic suprachiasmatic nucleus synchronizes with light-dark cycles,while peripheral tissue clocks are influenced by cues such as feeding times.Circadian disruption,linked to modern lifestyle factors like night shift work,correlates with adverse health outcomes,including metabolic syndrome,cardiovascular diseases,infec-tions,and cancer.We explored the molecular mechanisms of circadian clock genes and their impact on metabolic disorders and cancer pathogenesis.Specific associ-ations between circadian disruption and endocrine tumors,spanning breast,ovarian,testicular,prostate,thyroid,pituitary,and adrenal gland cancers,are highlighted.Shift work is associated with increased breast cancer risk,with PER genes influencing tumor progression and drug resistance.CLOCK gene expression correlates with cisplatin resistance in ovarian cancer,while factors like aging and intermittent fasting affect prostate cancer.Our review underscored the intricate interplay between circadian rhythms and cancer,involving the regulation of the cell cycle,DNA repair,metabolism,immune function,and the tumor microenvir-onment.We advocated for integrating biological timing into clinical consider-ations for personalized healthcare,proposing that understanding these connec-tions could lead to novel therapeutic approaches.Evidence supports circadian rhythm-focused therapies,particularly chronotherapy,for treating endocrine tumors.Our review called for further research to uncover detailed connections between circadian clocks and cancer,providing essential insights for targeted treatments.We emphasized the importance of public health interventions to mitigate lifestyle-related circadian disruptions and underscored the critical role of circadian rhythms in disease mechanisms and therapeutic interventions.
基金the financial support from Natural Science Foundation of Jiangsu Province(BK20210456)the National Natural Science Foundation of China(32201988,31972052,32021005,31820103010)+4 种基金the Fundamental Research Funds for the Central Universities(JUSRP22006,JUSRP51501)the China National Postdoctoral Program for Innovative Talents(BX2021114)China Postdoctoral Science Foundation(2021M691290)the Postdoctoral Science Foundation of Jiangsu Province(2021K127B)the Program of Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu Province。
文摘Gut microbiome is indispensable for maintaining normal brain function.Specifically,gut microbiota plays a causal role in sleep deprivation(SD)-induced cognitive impairment.In this study,neurobehavioral effects of the Bifidobacterium breve strain(CCFM1025)were assessed in sleep-deprived mice.CCFM1025 improved the body weight and food and water intake of the mice.It also alleviated SD-induced cognitive behavioural abnormalities(in the novel object recognition test),but did not show beneficial effects on mood-and spatial memory-related behaviours.CCFM1025 significantly altered the gut microbial composition and genome function.Key microbial metabolites that may regulate sleep function were also identified,such as isovaleric acid andγ-aminobutyric acid in the gut and purine metabolites in the serum.Those metabolites may participate in gutbrain communication by acting on the striatal melatonin system,for example to increase melatonin levels,and by regulating the expression of circadian clock genes such as those encoding the adenosine A2A receptor and period circadian regulator 1.Collectively,administration of probiotics alleviated cognitive impairment and circadian rhythm disturbance induced by SD via modulation of gut microbiome and its metabolites.These findings may help guide the treatment of insomnia or other sleep disorders via dietary strategies.
基金This work was supported by Laboratory of Lingnan Modern Agriculture Project(NZ2021001)State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources(SKICUSAa202007)+1 种基金Natural Science Foundation of Guangdong Province(2022A1515011027,2021A1515012148)the Double Firstclass Discipline Promotion Project(2023B10564004).
文摘Precise timing of flowering in plants is critical for their growth and reproductive processes.One factor controlling flowering time is the cycle of light and darkness within a day,known as the photoperiod.Plants are classified into long-day,short-day,and day-neutral plants based on light requirements for floral initiation.Although the molecular mechanisms that govern this differentiation remain incompletely understood,studies have consistently shown that the circadian clock plays a central role in regulating photoperiod response across diverse plant species.However,there is a scarcity of reviews describing the regulatory network linking the circadian clock with photoperiodic flowering.This review summarizes that regulatory network,focusing on the distinct roles of clock genes in long-day and short-day plants.We also discuss the strategies of clock gene mutations contributing to geographic variation in longday and short-day crops.
基金supported by the Chinese Scholarship Council(No.202206240086)Zhejiang Province Public Welfare Technology Application Research Project in China(No.TGY23H160090 and No.LGF21H160029)+1 种基金Taizhou Science and Technology Project,Zhejiang Province(No.20ywb12)Program for Talents of Chongqing University Three Gorges Hospital(No.2022YJKYXM-036).
文摘Aging and circadian rhythms have been connected for decades,but their molecular interaction has remained unknown,especially for cancers.In this situation,we summarized the current research actuality and problems in this field using the bibliometric analysis.Publications in the PubMed and Web of Science databases were retrieved.Overall,there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer.Researchers from USA,Germany,Italy,China and England have greater studies than others.Top three publication institutions are University of California System,UDICE-French Research Universities and University of Texas System.Current research hotspots include oxidative stress,breast cancer,melatonin,cell cycle,calorie restriction,prostate cancer and NF-κB.In conclusion,results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer.These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.
基金funded by the National Nature Science Foundation of China(No.82360295 and No.82060276)the Science and Technology Foundation Project of Guizhou Provincial Health Commission(gzwkj2024-150)+1 种基金the Doctor Start-up Fund of Affliated Hospital of Guizhou Medical University(gyfybsky-2023-03)the Science and Technology Department of Guizhou Province(QianKeHeJiChu-ZK[2021]YiBan382).
文摘In order to explore the impact of circadian disturbance on erectile function,we randomly divided 24 adult male rats into groups of control(light on at 8:00 a.m.and off at 8:00 p.m.),dark/dark(DD;constant dark),light/light(LL;constant light),and shift dark/light(DL;light off at 8:00 a.m.and on at 8:0o p.m.).Four weeks later,erectile function was measured and corpora cavernosa were harvested for analysis.The maximum intracavernous pressure(mlcP)and mCP/mean arterial pressure(MAP)ratio in the DD,LL,and DL groups were significantly lower than that in the control group.The LL and DL groups showed significantly attenuated endothelial nitric oxide synthase(eNOS),while DD,LL,and DL showed reduced neuronal nitric oxide synthase(nNOS)at both mRNA and protein levels.The production of nitric oxide(NO)and cyclic guanosinemonophosphate(cGMP)was inhibited by altered light/dark cycles to varying degrees.Circadian disturbance impaired endothelial function and contributed to erectile dysfunction.For the core circadian elements,mRNA expression of circadian locomotor output cycles kaput(Clock)and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1(Bmal1)was elevated in the DL group,but their protein expression was not significantly changed.DD,LL,and DL increased period 1(Per1)and Per3 levels,while LL and DL increased PER1 levels.No significant difference was found for Per2levels,and PER2 and PER3 concentrations were not significantly changed.Moreover,LL and DL significantly increased cryptochrome-1(CRY1)and CRY2 at both mRNA and protein levels.The altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial function.Meanwhile,the core circadian elements were detected in the corpora cavernosa,but these were disrupted.However,which circadian element regulates erectile function and how it works need further analysis.
