Circadian clock is an internal mechanism evolved to adapt to cyclic environmental changes, especially diurnal changes. Keeping the internal clock in synchronization with the external clock is essential for health. Mismatch of the clocks due to phase shift or disruption of molecular clocks may lead to circadian disorders, including abnormal sleep-wake cycles, as well as disrupted rhythms in hormone secretion, blood pressure, heart rate, body temperature, etc. Long-term circadian disorders are risk factors for various common critical diseases such as metabolic diseases, cardiovascular diseases, and tumor. To prevent or treat the circadian disorders, scientists have conducted extensive research on the function of circadian clocks and their roles in the development of diseases, and screened hundreds of thousands of compounds to find candidates to regulate circadian rhythms. In addition, melatonin, light therapy, exercise therapy, timing and composition of food also play a certain role in relieving associated symptoms. Here, we summarized the progress of both drug- and non-drug-based approaches to prevent and treat circadian clock disorders.
Circadian Rhythm ; Circadian Clocks ; Melatonin/physiology*

Circadian Clocks ; ARNTL Transcription Factors

Shift workers often experience problems associated with circadian disruption associated with artificial light at night and nocturia is commonly noted in night-shift workers. Nocturia associated with circadian disruption is due to increased urine production of the kidney and decreased storage function of the bladder. A recent discovery of peripheral clock genes in the bladder and their role in contractile property of the bladder support that micturition is closely related to the circadian rhythm. Moreover, there are clinical studies showed that shift workers more often experienced nocturia due to circadian disruption. However, comparing with other health problems, concerns on nocturia and voiding dysfunction associated with circadian disruption are insufficient. Therefore, further studies about voiding dysfunction associated with the circadian disruption in shift workers are necessary.
Circadian Clocks ; Circadian Rhythm ; Kidney ; Nocturia ; Urinary Bladder ; Urination

Circadian clock is an internal autonomous time-keeping system, including central clocks located in the suprachiasmatic nucleus (SCN) and peripheral clocks. The molecular circadian clock consists of a set of interlocking transcriptional-translational feedback loops that take the clock-controlled genes 24 h to oscillate. The core mechanism of molecular circadian clock is that CLOCK/BMAL1 dimer activates the transcription of cryptochromes (CRYs) and Periods (PERs), which act as transcriptional repressors of further CLOCK/BMAL1-mediated transcription. In addition to this basic clock, there is an additional sub-loop of REV-ERBα and RORα regulating the transcription of BMAL1. Approximately 80% protein-coding genes demonstrate significant rhythmicity. The earth rotation is responsible for the generation of the daily circadian rhythms. To coordinate metabolic balance and energy availability, almost all organisms adapt to the rhythm. Studies have shown that circadian clock integrating with metabolic homeostasis increases the efficiency of energy usage and coordinates with different organs in order to adapt to internal physiology and external environment soon. As the central organ of metabolism, the liver performs various physiological activities nearly all controlled by the circadian clock. There are multiple interactive regulation mechanisms between the circadian clock and the regulation of liver metabolism. The misalignment of metabolism with tissue circadian is identified as a high-risk factor of metabolic diseases. This article reviews the recent studies on circadian physiological regulation of liver glucose, lipid and protein metabolism and emphasizes oscillation of mitochondrial function. We also take an outlook for new methods and application of circadian clock research in the future.
CLOCK Proteins ; Circadian Clocks/genetics* ; Circadian Rhythm ; Liver ; Suprachiasmatic Nucleus

Cardiovascular Diseases ; Cardiovascular System ; Circadian Clocks/genetics* ; Circadian Rhythm ; Humans

Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In this review, we briefly introduce circadian clocks and their organization in mammals. We then summarize known daily or circadian variations in urinary function. Importantly, recent findings by others as well as results obtained by us suggest an active role of circadian clock genes in various urinary functions. Finally, we discuss possible research avenues for the circadian control of urinary function.
Biological Clocks ; Circadian Clocks ; Circadian Rhythm ; Humans ; Mammals ; Physiological Processes ; Rodentia ; Urinary Bladder ; Urination

OBJECTIVES: To investigate the effects of KCl on regulation of circadian gene CLOCK expression, we observed whether induction of CLOCK is influenced by KCl depolarization in B35 rat neuroblastoma cells. METHODS: B35 rat neuroblastoma cells were grown in Dulbecco's modified Eagle's medium supplemented with 10% FBS and 1% penicillin-streptomycin in a 37 degrees C humidified incubator with 5% CO2. Inhibitors including cycloheximide and actinomycin D were pretreated 1 hour before treatment with 50mM KCl. Immunoblotting with anti-CLOCK antibody was done. RESULTS: CLCOK is induced by 50 mM KCl in B35 Rat Neuroblastoma cells, and a maximal induction in CLOCK level reached peak at 8 to 20 hours. The pretreatment of cycloheximide and actinomycin D prevented the induction of CLOCK by 50 mM KCl. CONCLUSION: We suggest that KCl depolarization may play critical roles in several aspects of the circadian gene CLOCK expression.
Animals ; Circadian Clocks ; Cycloheximide ; Dactinomycin ; Immunoblotting ; Incubators ; Neuroblastoma* ; Rats*

Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. Circadian rhythm is controlled by the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and the peripheral clocks in various tissues. More importantly, the central clock can integrate photic/nonphotic signals to generate rhythmic outputs, and then drive the slave oscillators in peripheral tissues through neuroendocrine and behavioral signals. Human reproductive activities, as some other physiological functions, are controlled by the biological clocks. Accumulating lines of epidemiological and genetic evidence indicate that disruption of circadian clock can be directly involved in multiple pathological processes, including infertility. In this review, we mainly discuss the presence of a circadian clock in reproductive tissues and its roles in follicles development, ovulation, spermatogenesis, fertilization and embryo implantation, etc. As the increased shift work and assisted reproductive technologies possibly disrupt circadian rhythmicity to impact reproduction, the importance of circadian rhythms should be highlighted in the regulation of reproductive process.
Animals ; Biological Clocks ; Circadian Rhythm ; Hypothalamus ; Light ; Reproduction ; Suprachiasmatic Nucleus

As jet lag of modern travel continues to spread, there has been an exponential growth in popular explanations of jet lag and recommendations for curing it. Some of this attention are misdirected, and many of those suggested solutions are misinformed. The author reviewed the basic science of jet lag and its practical outcome. The jet lag symptoms stemed from several factors, including high-altitude flying, lag effect, and sleep loss before departure and on the aircraft, especially during night flight. Jet lag has three major components; including external desynchronization, internal desynchronization, and sleep loss. Although external desynchronization is the major culprit, it is not at all uncommon for travelers to experience difficulty falling asleep of remaining asleep because of gastrointestinal distress, uncooperative bladders, or nagging headaches, Such unwanted intrusions most likely to reflect the general influence of internal desynchronization. From the free-running subjects, the data has revealed that sleep tendency, sleepiness, the spontaneous duration of sleep, and REM sleep propensity, each varied markedly with the endogenous circadian phase of the temperature cycle, despite the facts that the average period of the sleep-wake cycle is different from that of the temperature cycle under these conditions. However, whereas the first ocurrence of slow wave sleep is usually associated with a fall in temperature, the amount of SWS is determined primarily by the length of prior wakefulness and not by circadian phase. Another factor to be considered for flight in either direction is the amount of prior sleep loss or time awake. An increase in sleep loss or time awake would be expected to reduce initial sleep latency and enhance the amount of SWS. By combining what we now know about the circadian characteristics of sleep and homeostatic process, many of the diverse findings about sleep after transmeridian flight can be explained. The severity of jet lag is directly related to two major variables that determine the reaction of the circadian system to any transmeridian flight, eg., the direction of flight, and the number of time zones crossed. Remaining factor is individual differences in resynchrnization. After a long flight, the circadian timing system and homeostatic process can combine with each other to produce a considerable reduction in well-being. The author suggested that by being exposed to local zeit-gebers and by being awake sufficient to get sleep until the night, sleep improves rapidly with resynchronization following time zone change.
Aircraft ; Circadian Clocks ; Circadian Rhythm* ; Diptera ; Fibrinogen ; Headache ; Individuality ; Sleep, REM ; Urinary Bladder ; Wakefulness

As a consequence of the Earth's rotation, almost all organisms experience day and night cycles within a 24-hr period. To adapt and synchronize biological rhythms to external daily cycles, organisms have evolved an internal time-keeping system. In mammals, the master circadian pacemaker residing in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus generates circadian rhythmicity and orchestrates numerous subsidiary local clocks in other regions of the brain and peripheral tissues. Regardless of their locations, these circadian clocks are cell-autonomous and self-sustainable, implicating rhythmic oscillations in a variety of biochemical and metabolic processes. A group of core clock genes provides interlocking molecular feedback loops that drive the circadian rhythm even at the single-cell level. In addition to the core transcription/translation feedback loops, post-translational modifications also contribute to the fine regulation of molecular circadian clocks. In this article, we briefly review the molecular mechanisms and post-translational modifications of mammalian circadian clock regulation. We also discuss the organization of and communication between central and peripheral circadian oscillators of the mammalian circadian clock.
Brain ; Circadian Clocks ; Circadian Rhythm ; Hypothalamus, Anterior ; Mammals ; Protein Processing, Post-Translational ; Suprachiasmatic Nucleus