Dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer’s disease.A predominant function of the retina is circadian synchronization,carrying information to the brain through the retinohypot...Dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer’s disease.A predominant function of the retina is circadian synchronization,carrying information to the brain through the retinohypothalamic tract,which projects to the suprachiasmatic nucleus.Notably,Alzheimer’s disease hallmarks,including amyloid-β,are present in the retinas of Alzheimer’s disease patients,followed/associated by structural and functional disturbances.However,the mechanistic link between circadian dysfunction and the pathological changes affecting the retina in Alzheimer’s disease is not fully understood,although some studies point to the possibility that retinal dysfunction could be considered an early pathological process that directly modulates the circadian rhythm.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
The interaction between host circadian rhythm and gut microbes through the gut-brain axis provides new clues for tea polyphenols to improve host health.Our present research showed that oolong tea polyphenols(OTP)impro...The interaction between host circadian rhythm and gut microbes through the gut-brain axis provides new clues for tea polyphenols to improve host health.Our present research showed that oolong tea polyphenols(OTP)improved the structural disorder of the intestinal flora caused by continuous darkness,thereby modulating the production of metabolites related to pyruvate metabolism,glycolysis/gluconeogenesis,and tryptophan metabolism to alleviate the steady-state imbalance.After fecal microbiota transplantation from the OTP group,the single-cell transcriptomic analysis revealed that OTP significantly increased the number of hypothalamus cell clusters,up-regulated the number of astrocytes and fibroblasts,and enhanced the expression of circadian rhythm genes Cry2,Per3,Bhlhe41,Nr1d1,Nr1d2,Dbp and Rorb in hypothalamic cells.Our results confirmed that OTP can actively improve the intestinal environmental state as well as internal/peripheral circadian rhythm disorders and cognitive impairment,with potential prebiotic functional characteristics to notably contribute to host health.展开更多
Autophagy is a widespread biological process that controls cellular growth,survival,development,and death.Circadian rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightn...Autophagy is a widespread biological process that controls cellular growth,survival,development,and death.Circadian rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and obscurity.Most of the fundamental physiological processes in mammals,such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism,are governed by circadian rhythms.Research has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal conditions.Autophagy can modulate circadian rhythms by breaking down proteins that regulate the circadian clock.The potential regulatory connection between the two has been a popular subject of clinical and fundamental research.Understanding the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the future.The present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm,as well as the pathological importance of the disrupted regulatory association between these two phenomena.展开更多
The interplay between the host circadian clock and microbiota has significant influences on host metabolism processes,and circadian desynchrony triggered by high-fat diet(HFD)is closely related to metabolic disorders....The interplay between the host circadian clock and microbiota has significant influences on host metabolism processes,and circadian desynchrony triggered by high-fat diet(HFD)is closely related to metabolic disorders.In this study,the modulatory effects of piperine(PIP)on lipid metabolism homeostasis,gut microbiota community and circadian rhythm of hepatic clock gene expressions in obese rats were investigated.The Sprague-Dawley(SD)rats were fed with normal diet(ND),HFD and HFD supplemented with PIP,respectively.After 9 weeks,rats were sacrificed with tissue and fecal samples collected for circadian analysis.Results showed that chronic PIP administration ameliorated the obesity-induced alterations in lipid metabolism and dysregulation of hepatic clock gene expressions in obese rats.The gut microbial communities studied through 16S rRNA sequencing showed that PIP ameliorated the imbalanced nicrobiota and recovered the circadian rhythm of Lactobacillaceae,Desulfovibrionaceae,Paraprevotellaceae,and Lachnospiraceae.The fecal metabolic profiles indicated that 3-dehydroshikimate,cytidine and lithocholyltaurine were altered,which were involved in the amino acid and fatty acid metabolism process.These findings could provide theoretical basis for PIP to work as functional food to alleviate the lipid metabolism disorder,circadian rhythm misalignment,and gut microbiota dysbiosis with wide applications in the food and pharmaceutic industries.展开更多
We have demonstrated the existence of a pyramid power and have revealed its characteristics by strictly scientific experiments using biosensors. We also revealed the existence of a Bio-Entanglement, an entangled relat...We have demonstrated the existence of a pyramid power and have revealed its characteristics by strictly scientific experiments using biosensors. We also revealed the existence of a Bio-Entanglement, an entangled relationship between biosensors. A parallel study of biosensors (edible cucumber slices) had also been conducted, and we found that the circadian rhythm of gas concentrations emitted from biosensors changes seasonally. The pyramid power and Bio-Entanglement did not change the number of cycles in the periodic approximation curve representing circadian rhythm. Therefore, in this paper we analyzed the influence of the pyramid power and Bio-Entanglement, i.e., their influence on the phase, amplitude, and correlation coefficient of the periodic approximation curve representing the circadian rhythm of emitted gas concentrations. The main results are as follows. 1) The pyramid power shifted the phase of the periodic approximation curve representing the circadian rhythm by 43 minutes. 2) The amplitude of the periodic approximation curve changed with the pyramid power and the Bio-Entanglement. The effect on the lower and upper sections of the biosensors stacked in two layers was different, with a tendency to increase the amplitude of the lower layer and decrease the amplitude of the upper layer. 3) The pyramid power and the Bio-Entanglement affected the correlation coefficient between gas concentration and the periodic approximation curve representing the circadian rhythm of gas concentration. The effect on the lower and upper layers of the biosensors was different, with a tendency for the lower layer correlation coefficient to be larger and the upper layer correlation coefficient to be smaller. Previously we demonstrated that the pyramid power and the Bio-Entanglement affect the ratio of gas concentration, i.e., psi index Ψ. In this paper we demonstrate for the first time that the pyramid power and the Bio-Entanglement affect time, i.e., phase difference.展开更多
Background: The circadian variation of childbirths has been described by several authors around the globe. De Graaf showed that hospital childbirths at night were associated with increased perinatal mortality and adve...Background: The circadian variation of childbirths has been described by several authors around the globe. De Graaf showed that hospital childbirths at night were associated with increased perinatal mortality and adverse perinatal outcome. To improve obstetric care, we carried out this study to evaluate the circadian rhythm of childbirths and to assess the outcome following variations in the time of childbirths during the day. Methods: It was a cross-sectional descriptive study at the Yaoundé Central Hospital (YCH), over a two years period. We collected data from files of women who delivered from the 1st of January 2017 to 31st December 2018. We included files of women who delivered at least at 28 weeks of pregnancy. We excluded files of those who delivered by elective caesarean section, those whose hour of delivery was not noted and those who delivered before reaching the hospital. Sociodemographic, obstetrical characteristics, and immediate prognosis were recorded. Data were entered into excel, then analysed with SPSS v23 software. Tools used to appreciate our results were means, median, number, percentage, P, and OR with its 95% confidence interval. The difference in p is significant if p is less than 5%. Results: We analyzed 6041 files bearing the time of birth. Childbirths took place at all hours of the day, but the times of the day where the highest numbers of births were recorded were 10, 11, 12, 13 (that’s 1pm), 14 (that’s 2 pm), 15 (that’s 3 pm), 16 (that’s 4 pm), 17 (that’s 5 pm) and 23 (that’s 11 pm) hours, with respectively 224 (3.7%), 277 (4.6%), 256 (4.2%), 265 (4.4%), 207 (3.4%), 255 (4.2%), 228 (3.8%), 216 (3.6%) and 226 (3.7%) births. The peak of births was at 11 am while the time of day where the lowest number of births was recorded was 6 pm, with 175 (2.9%) births. The mean age of participants was 27.34 ± 6.03 years with extremes of 13 and 49, with 87.6% between 20 to 39 years. Sociodemographic characteristics of participants, prematurity and bleeding during delivery, had no dependence on the time of delivery. Perineal tear, duration of observation, Apgar score of the newborn, birthweight, delivery mode, health personnel who performed the delivery, and episiotomyseemed to be influenced by the time of delivery. Daily shifts were not independently associated with the poor Apgar score (0 - 6) at 5 mins, when adjusted for all other factors (p = 0.109). Conclusion: Childbirths were more frequent between 10 am and 5 pm. The period where episiotomy was most performed is the same as when there was macrosomia childbirth. Tears of the perineum are more frequent between 2 pm and 10 pm. There was no independent association between Daily shifts and poor Apgar score. The poor APGAR score would be more related to low birth weight.展开更多
Light fl ux and quality are crucial factor for setting endogenous plant circadian rhythms.Evaluating the daily rhythmicity of leaf chlorophyll content is an eff ective method to monitor the plant physiological endogen...Light fl ux and quality are crucial factor for setting endogenous plant circadian rhythms.Evaluating the daily rhythmicity of leaf chlorophyll content is an eff ective method to monitor the plant physiological endogenous clock in response to environmental signals such as light availability/quality.Here,we used a leaf-clip sensor to monitor diurnal rhythms in the content of chlorophyll and fl avonoids such as fl avonols and anthocyanins in three green-(Ailanthus altissima,Tilia platyphyllos and Platanus×acerifolia)and two red-leafed(Acer platanoides cv.Crimson King and Prunus cerasifera var.pissardii)tree species,adapted to sun(L)or shade(S).Signifi cant diff erences in chlorophyll content(Chl)and its variations during the day were observed among treatments in all the analyzed species.S-plants had more Chl than L-plants irrespective of leaf color,and Chl variations were more distinct during the day than in L-plants.In particular,contents were lowest in the morning(9:00)and in the middle of the day(at 12:00 and 15:00),and the highest at dusk(21:00).The less evident trends in Chl variation in L-plants were attributed to a decrease in Chl content in high light,which likely masked any increases in the shaded counterparts during the afternoon.Daily fl avonol levels did not vary no notably during the day.In sun-exposed red leaves,anthocyanins partially screened mesophyll cells from incident light,and its levels were similar to the Chl dynamics in the shaded counterparts.This study provides new bases for further work on endogenous rhythms of plant pigments and improves our understanding of plant physiology in the context of day/night rhythmicity.展开更多
Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a r...Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a rat model of HIBD,up-regulation of microRNA-325(miR-325)in the pineal gland is responsible for the suppression of Aanat,a key enzyme involved in melatonin synthesis and circadian rhythm regulation.To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD,we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University(Dushuhu Branch)in 2019.We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD.Furthermore,a luciferase reporter gene assay revealed that LIM homeobox 3(LHX3)is a novel downstream target of miR-325.In addition,in miR-325 knock-down mice,the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland.We established a neonatal mouse model of HIBD by performing doublelayer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours.Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions.Finally,we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3.Taken together,our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD.The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University(approval No.2015028)on July 20,2015.Animal experiments were approved by Animal Care and Use Committee,School of Medicine,Soochow University,China(approval No.XD-2016-1)on January 15,2016.展开更多
Many organisms have evolved an approximately 24-hour circadian rhythm that allows them to achieve internal physiological homeostasis with external environment.Suprachiasmatic nucleus(SCN) is the central pacemaker of c...Many organisms have evolved an approximately 24-hour circadian rhythm that allows them to achieve internal physiological homeostasis with external environment.Suprachiasmatic nucleus(SCN) is the central pacemaker of circadian rhythm,and its activity is entrained to the external light-dark cycle.The SCN controls circadian rhythm through regulating the synthesis of melatonin by pineal gland via a multisynaptic pathway.Light,especially shortwavelength blue light,is the most potent environmental time cue in circadian photoentrainment.Recently,the discovery of a novel type of retinal photoreceptors,intrinsically photosensitive retinal ganglion cells,sheds light on the mechanism of circadian photoentrainment and raises concerns about the effect of ocular diseases on circadian system.With age,light transmittance is significantly decreased due to the aging of crystalline lens,thus possibly resulting in progressive loss of circadian photoreception.In the current review,we summarize the circadian physiology,highlight the important role of light in circadian rhythm regulation,discuss about the correlation between age-related cataract and sleep disorders,and compare the effect of blue light-filtering intraocular lenses(lOLs) and ultraviolet only filtering lOLs on circadian rhythm.展开更多
The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus,and it synchronizes the peripheral clocks in other tissues.Circadian clock genes and clock-contr...The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus,and it synchronizes the peripheral clocks in other tissues.Circadian clock genes and clock-controlled genes exist in almost all cell types.They have an essential role in many physiological processes,including lipid metabolism in the liver,regulation of the immune system,and the severity of infections.In addition,circadian rhythm genes can stimulate the immune response of host cells to virus infection.Hepatitis B virus(HBV)infection is the leading cause of liver disease and liver cancer globally.HBV infection depends on the host cell,and hepatocyte circadian rhythm genes are associated with HBV replication,survival,and spread.The core circadian rhythm proteins,REV-ERB and brain and muscle ARNTL-like protein 1,have a crucial role in HBV replication in hepatocytes.In addition to influencing the virus’s life cycle,the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines.Therefore,it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment.For these reasons,understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy.Therefore,this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.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
Vegetables and fruits are known to have long-lasting biological reactions even after harvesting. Volatile components may be released as a biological response to stimulation or injury. We measured the concentrations of...Vegetables and fruits are known to have long-lasting biological reactions even after harvesting. Volatile components may be released as a biological response to stimulation or injury. We measured the concentrations of volatiles released from the cut surfaces of cucumbers after their harvest and analyzed the relationship between the time the cucumbers were cut and gas concentrations. The results showed that gas concentrations indicate a circadian rhythm. We previously reported that the circadian rhythm of gas concentrations was 6 hours per cycle in the summer, i.e., from the vernal equinox to the autumnal equinox, and 24 hours per cycle in the winter, i.e., from the autumn equinox to the vernal equinox. We analyzed the gas concentrations emitted from cucumber sections in more detail in this paper and found that the circadian rhythms differ among winter, spring, summer, and autumn seasons. We found that one cycle of the circadian rhythm was 8 hours in winter, 6 hours in spring, 24 hours in summer, and a mixed cycle of 24 and 12 hours in autumn.展开更多
The neuropsychiatric disease named obsessive-compulsive disorder is composed by obsessions and/or compulsions.Obsessive-compulsive disorder etiologies are undefined.However,numerous mechanisms in several localizations...The neuropsychiatric disease named obsessive-compulsive disorder is composed by obsessions and/or compulsions.Obsessive-compulsive disorder etiologies are undefined.However,numerous mechanisms in several localizations are implicated.Some studies showed that both glutamate,inflammatory factors and oxidative stress could have main functions in obsessive-compulsive disorder.Glycogen synthase kinase-3β,the major negative controller of the WNT/β-catenin pathway is upregulated in obsessive-compulsive disorder.In obsessive-compulsive disorder,some studies presented the actions of the different circadian clock genes.WNT/β-catenin pathway and circadian clock genes appear to be intricate.Thus,this review focuses on the interaction between circadian clock genes and the WNT/β-catenin pathway in obsessive-compulsive disorder.展开更多
Background:Corticotropin-releasing hormone(CRH),the major secretagogue of the hypothalamic-pituitary-adrenal(HPA)axis,is intricately intertwined with the clock genes to regulate the circadian rhythm of various body fu...Background:Corticotropin-releasing hormone(CRH),the major secretagogue of the hypothalamic-pituitary-adrenal(HPA)axis,is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions.N6-methyladenosine(m^(6)A)RNA methylation is involved in the regulation of circadian rhythm,yet it remains unknown whether CRH expression and m^(6)A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress.Results:Chronic exposure to corticosterone(CORT)eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken.The circadian rhythms of clock genes in hippocampus,hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens.The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened,together with mRNA of other feeding-related neuropeptides.Interestingly,hypothalamic m^(6)A level oscillates in an opposite pattern to CRH mRNA,with lowestm^(6)A level after midnight(ZT18)corresponding to the peak of CRH mRNA before dawn(ZT22).CORT diminished the circadian rhythm of m^(6)A methylation with significantly increased level at night.Further site-specific m^(6)A analysis on 3’UTR of CRH mRNA indicates that higher m^(6)A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night(ZT18 and ZT22).Conclusions:Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus,leading to dysfunction of HPA axis in the chicken.RNA m^(6)A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions.展开更多
OBJECTIVE Dysregulation of circadian rhythms is associated with metabolic dysfunction,yet it is unclear whether enhancing clock function by small molecules can ameliorate metabolic disorders.METHODS We used an unbiase...OBJECTIVE Dysregulation of circadian rhythms is associated with metabolic dysfunction,yet it is unclear whether enhancing clock function by small molecules can ameliorate metabolic disorders.METHODS We used an unbiased chemical screen in fibroblasts expressing PER2::Luc to identify the Clock amplitude-Enhancing Small Mole⁃cule.In diet-induced obese mice and DB/DB mutant mice,we evaluated the effects of the Clock amplitude-Enhancing small Molecule on metabolic syndrome and locomotor activity.RESULTS We identified Nobiletin(NOB),a natural poly⁃methoxylated flavone,as a Clock amplitude-Enhancing Small Molecule by an unbiased chemical screen.In diet-induced obese mice,NOB strongly improved metabolic syndrome and enhanced locomotor activity in a Clock gene-dependent manner.Moreover,the clock is also required for the beneficial effects of NOB on metabolic disorders in DB/DB mutant mice.Notably,NOB enhanced clock protein levels and reprogramed metabolic gene expressions in the liver.Finally,we revealed retinoid acid receptor-related orphan receptors(RORα/γ)as direct targets of NOB.CONCLUSION Altogether,our results demonstrate that a pharmacological intervention that enhances circadian rhythms by small molecule may be as a novel strategy for combating metabolic disease.展开更多
Purpose:Patient body temperature was monitored after cardiac valve replacement,in order to explore the characteristics of body-temperature circadian rhythm and the factors influencing that rhythm.Methods:A cohort of 6...Purpose:Patient body temperature was monitored after cardiac valve replacement,in order to explore the characteristics of body-temperature circadian rhythm and the factors influencing that rhythm.Methods:A cohort of 67 patients who received cardiac valve replacement in a Fuzhou,Fujian province,China,general hospital underwent temperature measurements and analysis(by cosine curve)of their body-temperature circadian rhythm.A biological rhythm model was established through principal component analysis and evaluation of biological rhythm features.Multiple circadian parameters were included through linear regression analysis.Results:Patients’temperature after cardiac valve replacement exhibited circadian characteristics(p<0.05),among which the scores of temperature mesor,amplitude,and acrophase were respectively(37.610.08),(0.100.09),and33(e355,e119).Body-temperature rhythms were influenced by both gender and cardiopulmonary bypass time(p<0.05).Conclusion:Although some patients’circadian characteristics disappeared after cardiac valve replacement,circadian rhythms remained intact for most patients.Measures that were found to mitigate body-temperature circadian rhythm disruption included building a natural rhythm of light/darkness and decreasing cardiopulmonary bypass time.展开更多
The basic rhythms of nature that left their imprint on the existence of all living organism on the Earth, arose under the influence of the Earth’s rotation relative to the Sun, the Moon and other planets and stars of...The basic rhythms of nature that left their imprint on the existence of all living organism on the Earth, arose under the influence of the Earth’s rotation relative to the Sun, the Moon and other planets and stars of the Universe. This periodicity gave rise to the rhythm that has become essential for their life. Life is a continual chemical process of building up and breaking down of organic substances, which results from the substance exchange between an organism and the environment. This makes it impossible for a living organism to exist without the external environment. Since 1978-1979 we have been carrying out a task-oriented research with the aim to approximate the moment when we are able to answer all these questions. Daily fluctuations of cardiac and motor activity of the fetus have been studied (uninterrupted daily recording of fetal ECG);polysomnography of nocturnal sleep was recorded;daily fluctuations of endocrine system activity in the pregnant were studied. A correlation was made between the functional state of maternal sleep-wakefulness biological rhythm, biological clock of the human fetus and the “light-darkness” cycle of a 24-hour solar day. In the process of the study we have developed an original method of day-to-day analysis of maternal and fetal ECGs. It has been established that a healthy fetus has distinct, diurnal variations of physiological functions. The fetal biorhythms coordinate with the status of the maternal organism being, however, in an opposite phase. The curve of the dynamics of fetal physiological system functioning shows a biphasic nature (one-phase in adults). “Active” and “quiet” (sleep-like) periods have been singled out in the human fetus. No reaction is observed in “quiet” periods. However, the “zero”-type fetal reaction recorded by us within the period from 2 p.m. to 9 p.m. does not indicate unsatisfactory condition of the fetus but rather is suggestive of a definite reduction of functional levels of the fetal physiological systems, which is necessary for vital activity. Although conventionally recognized as an indicator of poor state of the fetus, this type only calls for precise attention when recorded in fetal “active” hours. The present study has been the first in the world’s medicine and biorhythmology to detect and establish the daily rhythms of cardiac and motor activity in the human fetus.展开更多
Background:According to the World Health Organization,about 350 million people worldwide are suffering from depression.It's reported that depression has been linked to several circadian rhythm perturbations,sugges...Background:According to the World Health Organization,about 350 million people worldwide are suffering from depression.It's reported that depression has been linked to several circadian rhythm perturbations,suggesting a disruption of the circadian clock system in affective disorders.The present study investigates the possible molecular mechanism of Shimian granules(SMG)in treating depression via restoring disrupted circadian rhythms.Method:Firstly,network pharmacology approach was used to identify the compounds and potential targets of SMG in TCMIP and BATMAN-TCM database.Secondly,the differential expression genes were obtained by gene expression profiling in GEO database(GSE56931,GSE98793).Further,protein-protein interactions(PPI)network was used to screen out core targets by STRING v11.Moreover,functional enrichment was carried out in DAVID database.Conclusively,the"herbs-compounds-targets-pathways"network was established to explore the mechanism of SMG in the treatment of depression.Result:It was found out that 65 compounds,18 targets and three pathways contributed to SMG in treating depression by regulating disrupted circadian rhythms,which might relate to core targets TNF,IL10,VDR in cAMP and calcium signaling pathway.Conclusion:Network pharmacology combined with gene expression profiling exhibited a powerful means to investigate the possible mechanism of formula,which contributes to theoretical basis for further study of SMG in the treatment of depression.展开更多
Clinically,glaucoma patients often suffer from circadian rhythm(CR)disorder.It is well-known that the imbalance of CR can be one of the triggering mechanisms of glaucoma.However,as a disease involving neurodegeneratio...Clinically,glaucoma patients often suffer from circadian rhythm(CR)disorder.It is well-known that the imbalance of CR can be one of the triggering mechanisms of glaucoma.However,as a disease involving neurodegeneration and mood dysregulation,glaucoma is more of a pathological process than a disease.Glaucoma pathogenesis exists throughout the whole process of life rhythm disorder,and its complex impact on CR deserves more attention.Glaucoma can cause CR disorder through a variety of mechanisms,while long-term CR disorder can lead to sleep disorder,depression,anxiety,metabolic syndrome and other related diseases,which in turn aggravate the process of glaucoma,forming a vicious cycle.Overall,glaucoma can affect the stability of CR not only by altering the optical signal reception,non-image-forming visual system,related hormone secretion and nerve damage,but also through mental disorders such as depression and anxiety.In this paper,we review the mechanism of glaucoma affecting CR in order to provide research ideas and therapeutic insights for glaucomatous CR disorder.展开更多
文摘Dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer’s disease.A predominant function of the retina is circadian synchronization,carrying information to the brain through the retinohypothalamic tract,which projects to the suprachiasmatic nucleus.Notably,Alzheimer’s disease hallmarks,including amyloid-β,are present in the retinas of Alzheimer’s disease patients,followed/associated by structural and functional disturbances.However,the mechanistic link between circadian dysfunction and the pathological changes affecting the retina in Alzheimer’s disease is not fully understood,although some studies point to the possibility that retinal dysfunction could be considered an early pathological process that directly modulates the circadian rhythm.
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sponsored by the Ningbo Natural Science Foundation(2021J107)。
文摘The interaction between host circadian rhythm and gut microbes through the gut-brain axis provides new clues for tea polyphenols to improve host health.Our present research showed that oolong tea polyphenols(OTP)improved the structural disorder of the intestinal flora caused by continuous darkness,thereby modulating the production of metabolites related to pyruvate metabolism,glycolysis/gluconeogenesis,and tryptophan metabolism to alleviate the steady-state imbalance.After fecal microbiota transplantation from the OTP group,the single-cell transcriptomic analysis revealed that OTP significantly increased the number of hypothalamus cell clusters,up-regulated the number of astrocytes and fibroblasts,and enhanced the expression of circadian rhythm genes Cry2,Per3,Bhlhe41,Nr1d1,Nr1d2,Dbp and Rorb in hypothalamic cells.Our results confirmed that OTP can actively improve the intestinal environmental state as well as internal/peripheral circadian rhythm disorders and cognitive impairment,with potential prebiotic functional characteristics to notably contribute to host health.
基金funded by the National Natural Science Foundation of China(Code No.82100954/81800924)Natural Science Foundation of Inner Mongolia Autonomous Region(Code No.2023QN08026)+3 种基金Key Research and Development Projects of Shaanxi Province(Code No.2022KW-12)The Basic and Natural Science Research Program of Shaanxi Province(Code No.2022JQ-915)Key Research and Development Program of Tibet Autonomous Region(XZ202001ZY0059G)New Technology and New Business Project of the Third Affiliated Hospital of Air Force Military Medical University(Code No.LX2021-416).
文摘Autophagy is a widespread biological process that controls cellular growth,survival,development,and death.Circadian rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and obscurity.Most of the fundamental physiological processes in mammals,such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism,are governed by circadian rhythms.Research has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal conditions.Autophagy can modulate circadian rhythms by breaking down proteins that regulate the circadian clock.The potential regulatory connection between the two has been a popular subject of clinical and fundamental research.Understanding the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the future.The present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm,as well as the pathological importance of the disrupted regulatory association between these two phenomena.
基金financially supported by the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2019ZT08N291)the National Natural Science Foundation of China (31901689)the Natural Science Foundation of Guangdong Province,China (2021A1515012124)。
文摘The interplay between the host circadian clock and microbiota has significant influences on host metabolism processes,and circadian desynchrony triggered by high-fat diet(HFD)is closely related to metabolic disorders.In this study,the modulatory effects of piperine(PIP)on lipid metabolism homeostasis,gut microbiota community and circadian rhythm of hepatic clock gene expressions in obese rats were investigated.The Sprague-Dawley(SD)rats were fed with normal diet(ND),HFD and HFD supplemented with PIP,respectively.After 9 weeks,rats were sacrificed with tissue and fecal samples collected for circadian analysis.Results showed that chronic PIP administration ameliorated the obesity-induced alterations in lipid metabolism and dysregulation of hepatic clock gene expressions in obese rats.The gut microbial communities studied through 16S rRNA sequencing showed that PIP ameliorated the imbalanced nicrobiota and recovered the circadian rhythm of Lactobacillaceae,Desulfovibrionaceae,Paraprevotellaceae,and Lachnospiraceae.The fecal metabolic profiles indicated that 3-dehydroshikimate,cytidine and lithocholyltaurine were altered,which were involved in the amino acid and fatty acid metabolism process.These findings could provide theoretical basis for PIP to work as functional food to alleviate the lipid metabolism disorder,circadian rhythm misalignment,and gut microbiota dysbiosis with wide applications in the food and pharmaceutic industries.
文摘We have demonstrated the existence of a pyramid power and have revealed its characteristics by strictly scientific experiments using biosensors. We also revealed the existence of a Bio-Entanglement, an entangled relationship between biosensors. A parallel study of biosensors (edible cucumber slices) had also been conducted, and we found that the circadian rhythm of gas concentrations emitted from biosensors changes seasonally. The pyramid power and Bio-Entanglement did not change the number of cycles in the periodic approximation curve representing circadian rhythm. Therefore, in this paper we analyzed the influence of the pyramid power and Bio-Entanglement, i.e., their influence on the phase, amplitude, and correlation coefficient of the periodic approximation curve representing the circadian rhythm of emitted gas concentrations. The main results are as follows. 1) The pyramid power shifted the phase of the periodic approximation curve representing the circadian rhythm by 43 minutes. 2) The amplitude of the periodic approximation curve changed with the pyramid power and the Bio-Entanglement. The effect on the lower and upper sections of the biosensors stacked in two layers was different, with a tendency to increase the amplitude of the lower layer and decrease the amplitude of the upper layer. 3) The pyramid power and the Bio-Entanglement affected the correlation coefficient between gas concentration and the periodic approximation curve representing the circadian rhythm of gas concentration. The effect on the lower and upper layers of the biosensors was different, with a tendency for the lower layer correlation coefficient to be larger and the upper layer correlation coefficient to be smaller. Previously we demonstrated that the pyramid power and the Bio-Entanglement affect the ratio of gas concentration, i.e., psi index Ψ. In this paper we demonstrate for the first time that the pyramid power and the Bio-Entanglement affect time, i.e., phase difference.
文摘Background: The circadian variation of childbirths has been described by several authors around the globe. De Graaf showed that hospital childbirths at night were associated with increased perinatal mortality and adverse perinatal outcome. To improve obstetric care, we carried out this study to evaluate the circadian rhythm of childbirths and to assess the outcome following variations in the time of childbirths during the day. Methods: It was a cross-sectional descriptive study at the Yaoundé Central Hospital (YCH), over a two years period. We collected data from files of women who delivered from the 1st of January 2017 to 31st December 2018. We included files of women who delivered at least at 28 weeks of pregnancy. We excluded files of those who delivered by elective caesarean section, those whose hour of delivery was not noted and those who delivered before reaching the hospital. Sociodemographic, obstetrical characteristics, and immediate prognosis were recorded. Data were entered into excel, then analysed with SPSS v23 software. Tools used to appreciate our results were means, median, number, percentage, P, and OR with its 95% confidence interval. The difference in p is significant if p is less than 5%. Results: We analyzed 6041 files bearing the time of birth. Childbirths took place at all hours of the day, but the times of the day where the highest numbers of births were recorded were 10, 11, 12, 13 (that’s 1pm), 14 (that’s 2 pm), 15 (that’s 3 pm), 16 (that’s 4 pm), 17 (that’s 5 pm) and 23 (that’s 11 pm) hours, with respectively 224 (3.7%), 277 (4.6%), 256 (4.2%), 265 (4.4%), 207 (3.4%), 255 (4.2%), 228 (3.8%), 216 (3.6%) and 226 (3.7%) births. The peak of births was at 11 am while the time of day where the lowest number of births was recorded was 6 pm, with 175 (2.9%) births. The mean age of participants was 27.34 ± 6.03 years with extremes of 13 and 49, with 87.6% between 20 to 39 years. Sociodemographic characteristics of participants, prematurity and bleeding during delivery, had no dependence on the time of delivery. Perineal tear, duration of observation, Apgar score of the newborn, birthweight, delivery mode, health personnel who performed the delivery, and episiotomyseemed to be influenced by the time of delivery. Daily shifts were not independently associated with the poor Apgar score (0 - 6) at 5 mins, when adjusted for all other factors (p = 0.109). Conclusion: Childbirths were more frequent between 10 am and 5 pm. The period where episiotomy was most performed is the same as when there was macrosomia childbirth. Tears of the perineum are more frequent between 2 pm and 10 pm. There was no independent association between Daily shifts and poor Apgar score. The poor APGAR score would be more related to low birth weight.
文摘Light fl ux and quality are crucial factor for setting endogenous plant circadian rhythms.Evaluating the daily rhythmicity of leaf chlorophyll content is an eff ective method to monitor the plant physiological endogenous clock in response to environmental signals such as light availability/quality.Here,we used a leaf-clip sensor to monitor diurnal rhythms in the content of chlorophyll and fl avonoids such as fl avonols and anthocyanins in three green-(Ailanthus altissima,Tilia platyphyllos and Platanus×acerifolia)and two red-leafed(Acer platanoides cv.Crimson King and Prunus cerasifera var.pissardii)tree species,adapted to sun(L)or shade(S).Signifi cant diff erences in chlorophyll content(Chl)and its variations during the day were observed among treatments in all the analyzed species.S-plants had more Chl than L-plants irrespective of leaf color,and Chl variations were more distinct during the day than in L-plants.In particular,contents were lowest in the morning(9:00)and in the middle of the day(at 12:00 and 15:00),and the highest at dusk(21:00).The less evident trends in Chl variation in L-plants were attributed to a decrease in Chl content in high light,which likely masked any increases in the shaded counterparts during the afternoon.Daily fl avonol levels did not vary no notably during the day.In sun-exposed red leaves,anthocyanins partially screened mesophyll cells from incident light,and its levels were similar to the Chl dynamics in the shaded counterparts.This study provides new bases for further work on endogenous rhythms of plant pigments and improves our understanding of plant physiology in the context of day/night rhythmicity.
基金This study was supported by the National Natural Science Foundation of China,Nos.81871193(to XD),81671532(to BS),81771625&81701490(to XF),81801505(to MG)Jiangsu Provincial Medical Youth Talent of China,Nos.QNRC2016763(to XD),QNRC2016758(to LXX),QNRC2016762(to ML)+7 种基金the Science and Technology Project of Suzhou City of China,No.SS201709(to XD)the Natural Science Foundation of Jiangsu Province of China,No.BK20180205(to XD)the Training Program Foundation for Health Talents of Gusu of China,No.GSWS2019049(to XD)the Jiangsu Provincial Key Medical Discipline of China,No.ZDXKA2016013(to XF)the Jiangsu Province Women and Children Health Research Project of China,No.F201750(to LXX)the Pediatric Clinical Center of Suzhou City of China,No.Szzx201504(to XF)Suzhou Industrial Technology Innovation Project of China,No.SYS201765(to LZ)the Project of Suzhou Science,Education and Health and Technology,China,No.KJXW2018018(to ML).
文摘Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a rat model of HIBD,up-regulation of microRNA-325(miR-325)in the pineal gland is responsible for the suppression of Aanat,a key enzyme involved in melatonin synthesis and circadian rhythm regulation.To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD,we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University(Dushuhu Branch)in 2019.We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD.Furthermore,a luciferase reporter gene assay revealed that LIM homeobox 3(LHX3)is a novel downstream target of miR-325.In addition,in miR-325 knock-down mice,the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland.We established a neonatal mouse model of HIBD by performing doublelayer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours.Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions.Finally,we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3.Taken together,our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD.The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University(approval No.2015028)on July 20,2015.Animal experiments were approved by Animal Care and Use Committee,School of Medicine,Soochow University,China(approval No.XD-2016-1)on January 15,2016.
文摘Many organisms have evolved an approximately 24-hour circadian rhythm that allows them to achieve internal physiological homeostasis with external environment.Suprachiasmatic nucleus(SCN) is the central pacemaker of circadian rhythm,and its activity is entrained to the external light-dark cycle.The SCN controls circadian rhythm through regulating the synthesis of melatonin by pineal gland via a multisynaptic pathway.Light,especially shortwavelength blue light,is the most potent environmental time cue in circadian photoentrainment.Recently,the discovery of a novel type of retinal photoreceptors,intrinsically photosensitive retinal ganglion cells,sheds light on the mechanism of circadian photoentrainment and raises concerns about the effect of ocular diseases on circadian system.With age,light transmittance is significantly decreased due to the aging of crystalline lens,thus possibly resulting in progressive loss of circadian photoreception.In the current review,we summarize the circadian physiology,highlight the important role of light in circadian rhythm regulation,discuss about the correlation between age-related cataract and sleep disorders,and compare the effect of blue light-filtering intraocular lenses(lOLs) and ultraviolet only filtering lOLs on circadian rhythm.
文摘The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus,and it synchronizes the peripheral clocks in other tissues.Circadian clock genes and clock-controlled genes exist in almost all cell types.They have an essential role in many physiological processes,including lipid metabolism in the liver,regulation of the immune system,and the severity of infections.In addition,circadian rhythm genes can stimulate the immune response of host cells to virus infection.Hepatitis B virus(HBV)infection is the leading cause of liver disease and liver cancer globally.HBV infection depends on the host cell,and hepatocyte circadian rhythm genes are associated with HBV replication,survival,and spread.The core circadian rhythm proteins,REV-ERB and brain and muscle ARNTL-like protein 1,have a crucial role in HBV replication in hepatocytes.In addition to influencing the virus’s life cycle,the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines.Therefore,it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment.For these reasons,understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy.Therefore,this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.
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Vegetables and fruits are known to have long-lasting biological reactions even after harvesting. Volatile components may be released as a biological response to stimulation or injury. We measured the concentrations of volatiles released from the cut surfaces of cucumbers after their harvest and analyzed the relationship between the time the cucumbers were cut and gas concentrations. The results showed that gas concentrations indicate a circadian rhythm. We previously reported that the circadian rhythm of gas concentrations was 6 hours per cycle in the summer, i.e., from the vernal equinox to the autumnal equinox, and 24 hours per cycle in the winter, i.e., from the autumn equinox to the vernal equinox. We analyzed the gas concentrations emitted from cucumber sections in more detail in this paper and found that the circadian rhythms differ among winter, spring, summer, and autumn seasons. We found that one cycle of the circadian rhythm was 8 hours in winter, 6 hours in spring, 24 hours in summer, and a mixed cycle of 24 and 12 hours in autumn.
文摘The neuropsychiatric disease named obsessive-compulsive disorder is composed by obsessions and/or compulsions.Obsessive-compulsive disorder etiologies are undefined.However,numerous mechanisms in several localizations are implicated.Some studies showed that both glutamate,inflammatory factors and oxidative stress could have main functions in obsessive-compulsive disorder.Glycogen synthase kinase-3β,the major negative controller of the WNT/β-catenin pathway is upregulated in obsessive-compulsive disorder.In obsessive-compulsive disorder,some studies presented the actions of the different circadian clock genes.WNT/β-catenin pathway and circadian clock genes appear to be intricate.Thus,this review focuses on the interaction between circadian clock genes and the WNT/β-catenin pathway in obsessive-compulsive disorder.
基金supported by the National Natural Science Foundation of China (31972638)the National Key Research and Development Program of China (2016YFD0500502)+2 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)the Postgraduate Research&Practice Innovation Program of Jiangsu Province (KYCX18_0716)Jiangsu Collaborative Innovation Center of Meat Production and Processing,Quality,Safety Control
文摘Background:Corticotropin-releasing hormone(CRH),the major secretagogue of the hypothalamic-pituitary-adrenal(HPA)axis,is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions.N6-methyladenosine(m^(6)A)RNA methylation is involved in the regulation of circadian rhythm,yet it remains unknown whether CRH expression and m^(6)A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress.Results:Chronic exposure to corticosterone(CORT)eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken.The circadian rhythms of clock genes in hippocampus,hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens.The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened,together with mRNA of other feeding-related neuropeptides.Interestingly,hypothalamic m^(6)A level oscillates in an opposite pattern to CRH mRNA,with lowestm^(6)A level after midnight(ZT18)corresponding to the peak of CRH mRNA before dawn(ZT22).CORT diminished the circadian rhythm of m^(6)A methylation with significantly increased level at night.Further site-specific m^(6)A analysis on 3’UTR of CRH mRNA indicates that higher m^(6)A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night(ZT18 and ZT22).Conclusions:Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus,leading to dysfunction of HPA axis in the chicken.RNA m^(6)A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions.
文摘OBJECTIVE Dysregulation of circadian rhythms is associated with metabolic dysfunction,yet it is unclear whether enhancing clock function by small molecules can ameliorate metabolic disorders.METHODS We used an unbiased chemical screen in fibroblasts expressing PER2::Luc to identify the Clock amplitude-Enhancing Small Mole⁃cule.In diet-induced obese mice and DB/DB mutant mice,we evaluated the effects of the Clock amplitude-Enhancing small Molecule on metabolic syndrome and locomotor activity.RESULTS We identified Nobiletin(NOB),a natural poly⁃methoxylated flavone,as a Clock amplitude-Enhancing Small Molecule by an unbiased chemical screen.In diet-induced obese mice,NOB strongly improved metabolic syndrome and enhanced locomotor activity in a Clock gene-dependent manner.Moreover,the clock is also required for the beneficial effects of NOB on metabolic disorders in DB/DB mutant mice.Notably,NOB enhanced clock protein levels and reprogramed metabolic gene expressions in the liver.Finally,we revealed retinoid acid receptor-related orphan receptors(RORα/γ)as direct targets of NOB.CONCLUSION Altogether,our results demonstrate that a pharmacological intervention that enhances circadian rhythms by small molecule may be as a novel strategy for combating metabolic disease.
基金This study was supported by Fujian,China,Provincial funds(2011-CX-24).
文摘Purpose:Patient body temperature was monitored after cardiac valve replacement,in order to explore the characteristics of body-temperature circadian rhythm and the factors influencing that rhythm.Methods:A cohort of 67 patients who received cardiac valve replacement in a Fuzhou,Fujian province,China,general hospital underwent temperature measurements and analysis(by cosine curve)of their body-temperature circadian rhythm.A biological rhythm model was established through principal component analysis and evaluation of biological rhythm features.Multiple circadian parameters were included through linear regression analysis.Results:Patients’temperature after cardiac valve replacement exhibited circadian characteristics(p<0.05),among which the scores of temperature mesor,amplitude,and acrophase were respectively(37.610.08),(0.100.09),and33(e355,e119).Body-temperature rhythms were influenced by both gender and cardiopulmonary bypass time(p<0.05).Conclusion:Although some patients’circadian characteristics disappeared after cardiac valve replacement,circadian rhythms remained intact for most patients.Measures that were found to mitigate body-temperature circadian rhythm disruption included building a natural rhythm of light/darkness and decreasing cardiopulmonary bypass time.
文摘The basic rhythms of nature that left their imprint on the existence of all living organism on the Earth, arose under the influence of the Earth’s rotation relative to the Sun, the Moon and other planets and stars of the Universe. This periodicity gave rise to the rhythm that has become essential for their life. Life is a continual chemical process of building up and breaking down of organic substances, which results from the substance exchange between an organism and the environment. This makes it impossible for a living organism to exist without the external environment. Since 1978-1979 we have been carrying out a task-oriented research with the aim to approximate the moment when we are able to answer all these questions. Daily fluctuations of cardiac and motor activity of the fetus have been studied (uninterrupted daily recording of fetal ECG);polysomnography of nocturnal sleep was recorded;daily fluctuations of endocrine system activity in the pregnant were studied. A correlation was made between the functional state of maternal sleep-wakefulness biological rhythm, biological clock of the human fetus and the “light-darkness” cycle of a 24-hour solar day. In the process of the study we have developed an original method of day-to-day analysis of maternal and fetal ECGs. It has been established that a healthy fetus has distinct, diurnal variations of physiological functions. The fetal biorhythms coordinate with the status of the maternal organism being, however, in an opposite phase. The curve of the dynamics of fetal physiological system functioning shows a biphasic nature (one-phase in adults). “Active” and “quiet” (sleep-like) periods have been singled out in the human fetus. No reaction is observed in “quiet” periods. However, the “zero”-type fetal reaction recorded by us within the period from 2 p.m. to 9 p.m. does not indicate unsatisfactory condition of the fetus but rather is suggestive of a definite reduction of functional levels of the fetal physiological systems, which is necessary for vital activity. Although conventionally recognized as an indicator of poor state of the fetus, this type only calls for precise attention when recorded in fetal “active” hours. The present study has been the first in the world’s medicine and biorhythmology to detect and establish the daily rhythms of cardiac and motor activity in the human fetus.
基金This research has been financially supported by the Special Support Scheme for Shaanxi Province,and the Subject Innovation Team of Shaanxi University of Chinese Medicine(#2019-YS01)Shaanxi province administration of traditional Chinese medicine(#2021-ZZ-JC018).
文摘Background:According to the World Health Organization,about 350 million people worldwide are suffering from depression.It's reported that depression has been linked to several circadian rhythm perturbations,suggesting a disruption of the circadian clock system in affective disorders.The present study investigates the possible molecular mechanism of Shimian granules(SMG)in treating depression via restoring disrupted circadian rhythms.Method:Firstly,network pharmacology approach was used to identify the compounds and potential targets of SMG in TCMIP and BATMAN-TCM database.Secondly,the differential expression genes were obtained by gene expression profiling in GEO database(GSE56931,GSE98793).Further,protein-protein interactions(PPI)network was used to screen out core targets by STRING v11.Moreover,functional enrichment was carried out in DAVID database.Conclusively,the"herbs-compounds-targets-pathways"network was established to explore the mechanism of SMG in the treatment of depression.Result:It was found out that 65 compounds,18 targets and three pathways contributed to SMG in treating depression by regulating disrupted circadian rhythms,which might relate to core targets TNF,IL10,VDR in cAMP and calcium signaling pathway.Conclusion:Network pharmacology combined with gene expression profiling exhibited a powerful means to investigate the possible mechanism of formula,which contributes to theoretical basis for further study of SMG in the treatment of depression.
基金supported by Regional Fund Project of National Natural Science Foundation of China(81860870)Program of Chinese medicine innovative-Backbone talents of China(Xiang CM[2019]67)+1 种基金Hunan Province"225"Program for Cultivation of High-level Health Talents(Xiang CM[2019]196)Open Fund Project of Hunan Provincial Engineering Technology Research Center for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases and visual function protection with Chinese Medicine(2018YZD02).
文摘Clinically,glaucoma patients often suffer from circadian rhythm(CR)disorder.It is well-known that the imbalance of CR can be one of the triggering mechanisms of glaucoma.However,as a disease involving neurodegeneration and mood dysregulation,glaucoma is more of a pathological process than a disease.Glaucoma pathogenesis exists throughout the whole process of life rhythm disorder,and its complex impact on CR deserves more attention.Glaucoma can cause CR disorder through a variety of mechanisms,while long-term CR disorder can lead to sleep disorder,depression,anxiety,metabolic syndrome and other related diseases,which in turn aggravate the process of glaucoma,forming a vicious cycle.Overall,glaucoma can affect the stability of CR not only by altering the optical signal reception,non-image-forming visual system,related hormone secretion and nerve damage,but also through mental disorders such as depression and anxiety.In this paper,we review the mechanism of glaucoma affecting CR in order to provide research ideas and therapeutic insights for glaucomatous CR disorder.
