Irisin/BDNF signaling in the muscle-brain axis and circadian system: A review

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.

Circadian rhythm disruption and endocrine-related tumors

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.

Hypothalamic circuits and aging:keeping the circadian clock updated

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

Circadian rhythm disruption and retinal dysfunction:a bidirectional link in Alzheimer’s disease?

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.

Probiotics administration alleviates cognitive impairment and circadian rhythm disturbance induced by sleep deprivation

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.

Unraveling links between aging,circadian rhythm and cancer:Insights from evidence-based analysis

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.

Flowering-time regulation by the circadian clock:From Arabidopsis to crops

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.

Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health

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.

The Regulatory Role and Mechanism of Circadian Rhythm in Hemoglobin Co-cultured Neurovascular Unit

Objective Intracranial hemorrhage(ICH),the second most common subtype of stroke,exacerbates the disruption of the blood-brain barrier(BBB),leading to vasogenic edema,plasma protein extravasation,and infiltration of neurotoxic substances.The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage.This study aimed to investigate the effect of circadian rhythms on BBB function,neuronal damage,and clearance capabilities.Methods The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH.After intervention with different light groups,neuronal apoptosis was determined,glial phagocytosis was analyzed,the expression of endogenous clearing-related proteins aquaporin 4(AQP4)and low-density lipoprotein receptor-related protein 1(LRP1)was detected by western blotting and immunofluorescence dual standard method,and the expression of the tight junction protein occludin and melatonin receptor 1A(MTNR1A)was quantitatively analyzed.Results Circadian rhythms play a key role in maintaining the integrity of the BBB,reducing oxidative stress-induced neuronal damage,and improving microglial phagocytosis.Meanwhile,the expression of occludin and MTNR1A in neurovascular unit(NVU)co-cultured with hemoglobin improved the expression of AQP4 and LRP1,the key proteins in the NVU's endogenous brain clearance system.Conclusion Circadian rhythm(alternating black and white light)protects the NVU BBB function after ICH,promotes the expression of proteins related to the clearance of the hematoma,provides new evidence for the clinical treatment of patients recovering from ICH,and improves the circadian rhythm to promote brain metabolism and hematoma clearance.

Piperine regulates the circadian rhythms of hepatic clock gene expressions and gut microbiota in high-fat diet-induced obese rats

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.

Capsaicin alleviates the hepatic clock gene disruption and gut microbiota dysbiosis in circadian rhythm disorder mouse model

As the body’s internal clock,the circadian rhythm regulates the energy expenditure,appetite,and sleep.There exists a close relationship between the host circadian rhythm and gut microbiota.In this work,a circadian disorder mouse model induced by constant darkness(CD)was constructed to investigate the regulating effects of capsaicin(CAP)on disturbances of metabolism homeostasis and gut microbiota in the respect of circadian rhythm-related mechanisms.Our results indicated that CAP reduced weight gain induced by circadian rhythm disorder in mice by inhibiting fat accumulation in liver and adipose tissue.The rhythmic expressions of circadian clock genes and lipid-metabolism related genes in liver were also recovered by CAP.Microbial study using 16S rRNA sequencing revealed that CAP modulated the gut microbiota richness,diversity and composition,and restored diurnal oscillations of gut microbes at the phylum and family level.These results indicated that CAP could alleviate CD-induced hepatic clock gene disruption and gut microbiota dysbiosis in mice,providing theoretical basis for CAP to be used as a muti-functional ingredient with great healthpromoting effects.

The modulatory effect of oolong tea polyphenols on intestinal flora and hypothalamus gene expression in a circadian rhythm disturbance mouse model

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.

Autophagy and circadian rhythms:interactions and clinical implications

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.

Corneal and intraocular pressure changes associated to the circadian rhythms:a narrative review

AIM:To synthesize the current body of research regarding the diurnal variations in intraocular pressure(IOP)and corneal biomechanical and morphological parameters,highlighting their significance in various eye conditions.METHODS:A comprehensive review of studies on the diurnal variations of IOP and corneal parameters was conducted.Tonometry findings from various studies were assessed,including the Goldmann applanation tonometry(GAT)and non-contact tonometers.Data on the variations in central corneal thickness(CCT),corneal curvature,and corneal biomechanics measured by the Ocular Response Analyzer system across different population groups was extracted and analyzed.RESULTS:In both healthy subjects and those with Fuchs dystrophy,IOP and CCT demonstrate marked diurnal declines.GAT remains the gold standard for tonometry,with the highest reliability.However,its measurements are influenced by CCT.Keratoconus patients and those with pseudoexfoliation showed significant diurnal variations in IOP.The biomechanical parameters,especially corneal hysteresis(CH)and the corneal resistance factor(CRF),largely remain stable throughout the day for most of eye conditions,with some exceptions.Notably,the corneal morphology diurnal variation,particularly curvature,yielded mixed conclusions across studies.CONCLUSION:Circadian rhythms significantly influence various corneal parameters,most notably IOP and CCT.Further studies should emphasize standardized approaches larger sample sizes,and delve deeper into less-explored areas,such as the effects of orthokeratology lenses on diurnal biomechanical shifts.

Regulation of circadian physiology and behavior by light in mammals:entrainment and masking

manifestation of circadian rhythms.The modern use of electric lights alters environmental lighting,leading to light exposure at inappropriate times to disturb circadian homeostasis for both human and wildlife.The light“pollution”and voluntary activities such as night shift work and transmeridian travelling have adverse consequences such as mood and metabolic disorders in humans.On the other hand,insufficient light exposure decreases neurotransmission from the locus ceruleus and dorsal raphe,leading to seasonal and nonseasonal affective disorders,while properly timed bright light is beneficial to mood and cognition.Given the critical and complex roles of light in mammalian physiology and behavior,it is essential to understand the underlying mechanisms.In this review,we discuss the neural mechanisms through which light regulates and dysregulates circadian rhythms in mammals.

Diff erences in pigment circadian rhythmicity in greenand red-leafed tree species in the sun and shade

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.

Major roles of the circadian clock in cancer

Circadian rhythms are natural rhythms that widely exist in all creatures,and regulate the processes and physiological functions of various biochemical reactions.The circadian clock is critical for cancer occurrence and progression.Its function is regulated by metabolic activities,and the expression and transcription of various genes.This review summarizes the composition of the circadian clock;the biological basis for its function;its relationship with,and mechanisms in,cancer;its various functions in different cancers;the effects of anti-tumor treatment;and potential therapeutic targets.Research in this area is expected to advance understanding of circadian locomotor output cycles kaput(CLOCK)and brain and muscle ARNT-like protein 1(BMAL1)in tumor diseases,and contribute to the development of new anti-tumor treatment strategies.

Potential Power of the Pyramidal Structure VII: Effects of Pyramid Power and Bio-Entanglement on the Circadian Rhythm of Biosensors

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.

Circadian Rhythm of Childbirths and Maternal and Neonatal Prognosis at the YaoundéCentral Hospital

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.

The role of circadian rhythm in breast cancer

The circadian rhythm is an endogenous time keeping system shared by most organisms. The circadian clock is comprised of both peripheral oscillators in most organ tissues of the body and a central pacemaker located in the suprachiasmatic nucleus （SCN） of the central nervous system. The circadian rhythm is crucial in maintaining the normal physiology of the organism including, but not limited to, cell proliferation, cell cycle progression, and cellular metabolism; whereas disruption of the circadian rhythm is closely related to multi-tumorigenesis. In the past several years, studies from different fields have revealed that the genetic or functional disruption of the molecular circadian rhythm has been found in various cancers, such as breast, prostate, and ovarian. In this review, we will investigate and present an overview of the current research on the influence of circadian rhythm regulating proteins on breast cancer.