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 rhythm is an internal autonomous timing mechanism formed by the body in response to changes of external environment. It participates in the regulations of various physiological activities, affecting the formation and outcome of various diseases in the human body. This paper summarizes the changes of local tissue rhythms in common disease states, such as oral and maxillofacial malformations, inflammation and malignant tumors. The importance of circadian clock system to the activities of oral and maxillofacial tissues are dialectically analyzed, mainly on the mechanisms of action in maintaining oral health and in affecting the processes of common oral diseases and oral-related systemic diseases. At the same time, chronological therapy and new strategies of prevention and treatment for oral-related diseases based on the changes in tissue rhythm are summarized and prospected to provide new ideas for maintaining oral and systemic health.
Circadian Clocks/physiology* ; Circadian Rhythm/physiology* ; Humans ; Inflammation ; Mouth Diseases ; Neoplasms

The circadian clock is an evolutionary molecular product that is associated with better adaptation to changes in the external environment. Disruption of the circadian rhythm plays a critical role in tumorigenesis of many kinds of cancers, including prostate cancer (PCa). Integrating circadian rhythm into PCa research not only brings a closer understanding of the mechanisms of PCa but also provides new and effective options for the precise treatment of patients with PCa. This review begins with patterns of the circadian clock, highlights the role of the disruption of circadian rhythms in PCa at the epidemiological and molecular levels, and discusses possible new approaches to PCa therapy that target the circadian clock.
Humans ; Male ; Carcinogenesis ; Circadian Clocks/physiology* ; Circadian Rhythm/physiology* ; Prostatic Neoplasms/physiopathology*

The animal time structure is a basic fact of life, no matter if one wants to study it or not. The time- dependent, mostly rhythmic, and thus to a certain degree predictable, variations of biochemical and physiological functions and of sensitivity and resistance to many environmental agents are often quite large and offer not only new insight into animal physiology and pathology but also diagnostic possibilities and therapeutic advantages. Chronobiology, chronophysiology and its subspecialities, like chronopharmacology and chronotherapy, will certainly play an important role in the clinical medicine of the future. Successful application of chronobiology to veterinary clinical medicine, however, depends critically on a thorough knowledge of its basic principles.
Animals ; Animals, Domestic/*physiology ; Behavior, Animal/*physiology ; Biological Clocks/*physiology ; Circadian Rhythm/*physiology ; Humans ; Photoperiod ; Seasons

The mammalian internal circadian clock system has been evolved to adapt to the diurnal changes in the internal and external environment of the organism to regulate diverse physiological functions, such as the sleep-wake cycle and feeding rhythm, thereby coordinating the rhythmic changes of energy demand and nutrition supply in each diurnal cycle. The circadian clock regulates glucose metabolism, lipid metabolism, and hormones secretion in diverse tissues and organs, including the liver, skeletal muscle, pancreas, heart, and vessels. As a special "organ" of the host, the gut microbiota, together with the intestinal microenvironment (tissues, cells, and metabolites) in a co-evolutionary process, constitutes a micro-ecosystem and plays an important role in the process of nutrient digestion and absorption in the intestine of the host. In recent years, accumulating evidence indicates that the compositions, quantities, colonization, and functional activities of the gut microbiota exhibit significant circadian variations, which are closely related to the changes of various physiological functions under the regulation of host circadian clock system. In addition, several studies have shown that the gut microbiota can produce many important metabolites such as the short-chain fatty acids through the degradation of indigestive dietary fibers. A portion of gut microbiota-derived metabolites can regulate the circadian clock system and metabolism of the host. This article mainly discusses the interaction between the host circadian clock system and the gut microbiota, and highlights its influence on energy metabolism of the host, providing a novel clues and thought for the prevention and treatment of metabolic diseases.
Animals ; Circadian Clocks/physiology* ; Circadian Rhythm/physiology* ; Ecosystem ; Energy Metabolism ; Gastrointestinal Microbiome/physiology* ; Lipid Metabolism/physiology* ; Mammals

Circadian clocks are the internal time-keeping mechanisms for organisms to synchronize their cellular and physiological processes to the daily light/dark cycles. The molecular mechanisms underlying circadian clocks are remarkably similar in eukaryotes. Neurospora crassa, a filamentous fungus, is one of the best understood model organisms for circadian research. In recent years, accumulating data have revealed complex regulation in the Neurospora circadian clock at transcriptional, posttranscriptional, post-translational and epigenetic levels. Here we review the recent progress towards our understanding of the molecular mechanism of the Neurospora circadian oscillator. These advances have provided novel insights and furthered our understanding of the mechanism of eukaryotic circadian clocks.
Circadian Clocks ; Epigenomics ; Neurospora ; genetics ; metabolism ; physiology ; Neurospora crassa ; genetics ; metabolism ; physiology

By means of a circadian clock system, all the living organisms on earth including human beings can anticipate the environmental rhythmic changes such as light/dark and warm/cold periods in a daily as well as in a yearly manner. Anticipating such environmental changes provide organisms with survival benefits via manifesting behavior and physiology at an advantageous time of the day and year. Cell-autonomous circadian oscillators, governed by transcriptional feedback loop composed of positive and negative elements, are organized into a hierarchical system throughout the organisms and generate an oscillatory expression of a clock gene by itself as well as clock controlled genes (ccgs) with a 24 hr periodicity. In the feedback loop, hetero-dimeric transcription factor complex induces the expression of negative regulatory proteins, which in turn represses the activity of transcription factors to inhibit their own transcription. Thus, for robust oscillatory rhythms of the expression of clock genes as well as ccgs, the precise control of subcellular localization and/or timely translocation of core clock protein are crucial. Here, we discuss how sub-cellular localization and nuclear translocation are controlled in a time-specific manner focusing on the negative regulatory clock proteins.
Circadian Clocks* ; Circadian Rhythm ; CLOCK Proteins ; Humans ; Periodicity ; Phosphorylation ; Physiology ; Protein Processing, Post-Translational ; Repressor Proteins* ; Transcription Factors

Developments of chronobiology abroad are forging ahead in elucidating the cellular and molecular basis and the influential factors of circadian clock such as light, jet lag, pharmaceutical. This article also reviews the influence of circadian system on human physiology and disease occurrence. The circadian-based therapy holds promising future and the research emphasis is on prognosis and prevention.
Biological Clocks ; Chronobiology Phenomena ; Circadian Rhythm ; physiology ; Drug Chronotherapy ; Jet Lag Syndrome

OBJECTIVE: To investigate the effect of circadian heart rate variation on short-term and long-term mortality in intensive care unit (ICU) patients. METHODS: A retrospective cohort study was conducted. A total of 32 536 ICU patients were recorded from 2001 to 2008 published by Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II v2.6) in April 2011. The circadian heart rate variation was defined as the ratio of mean nighttime (23:00 to 07:00) heart rate to mean daytime (07:00 to 23:00) heart rate. The 28-day mortality and 1-year mortality were defined as outcome events. The information such as age, gender, ethnicity, first sequential organ failure assessment (SOFA) score, first simplified acute physiology score I (SAPS I), usage of sedatives and catecholamines within 24 hours admission of ICU, clinical complications [hypertension, chronic obstructive pulmonary disease (COPD), diabetes with or without complications, congestive heart failure, liver disease, renal failure, etc.], and the complete heart rate records within 24 hours after ICU admission were collected. Cox proportional risk regression models were used to investigate the association between circadian heart rate variation and 28-day mortality and 1-year mortality in ICU patients. Besides, subgroup analysis was also performed in patients with different first SOFA scores. RESULTS: Totally 15 382 ICU patients in MIMIC-II database were enrolled, excluding the patients without heart rate records or death records, using pacemaker with arrhythmia, without SOFA or SAPS I score records. Finally, 9 439 patients were enrolled in the study cohort. (1) Cox regression analysis of the whole patient showed that the higher circadian heart rate variation was correlated with the increased 28-day mortality [hazard ratio (HR) = 1.613, 95% confidence interval (95%CI) was 1.338-1.943, P < 0.001] and 1-year mortality (HR = 1.573, 95%CI was 1.296-1.908, P < 0.001). After adjustment for demographic factors (age, gender and ethnicity), severity of illness (SOFA and SAPS I scores), clinical complications (hypertension, COPD, diabetes with or without complications, congestive heart failure, liver disease, renal failure, etc.), and influence of medications (sedatives and catecholamines), the night-day heart rate ratio was also correlated with 28-day mortality (HR = 1.256, 95%CI was 1.018-1.549, P = 0.033) and 1-year mortality (HR = 1.249, 95%CI was 1.010-1.545, P = 0.040). (2) According to the SOFA score (median value of 5), the patients were divided into two subgroups, in which 5 478 patients with SOFA score ≤ 5 and 3 961 patients with SOFA score > 5. Cox regression subgroup analysis showed that circadian heart rate variation was related with higher 28-day mortality (HR = 1.430, 95%CI was 1.164-1.756, P = 0.001) and 1-year mortality (HR = 1.393, 95%CI was 1.123-1.729, P = 0.003) in patients with SOFA score > 5. After adjustment for covariates, the 28-day mortality (HR = 1.279, 95%CI was 1.032-1.584, P = 0.025) and 1-year mortality (HR = 1.255, 95%CI was 1.010-1.558, P = 0.040) also increased with the increasing of night-day heart rate ratio in patients with SOFA score > 5. However, the relationships did not exist in patients with SOFA score ≤ 5. CONCLUSIONS In ICU patients, the 28-day mortality and 1-year mortality increase with the higher circadian heart rate variation, which indicates that the circadian heart rate variation in ICU patients is positively correlated with the short-term and long-term mortality, especially in patients with relatively severe illness.
Circadian Clocks ; Critical Care ; Heart Rate/physiology* ; Humans ; Intensive Care Units ; Mortality/trends* ; Organ Dysfunction Scores ; Prognosis ; Retrospective Studies

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 the present study, we demonstrate that Per2 promoter activity clearly oscillates in neonate and adult bladders cultured ex vivo from Per2::Luc knock-in mice. In subsequent experiments, we show that multiple local oscillators are operating in all the bladder tissues (detrusor, sphincter and urothelim) and the lumbar spinal cord (L4-5) but not in the pontine micturition center or the ventrolateral periaqueductal gray of the brain. Accordingly, the water intake and urine volume exhibited daily and circadian variations in young adult wild-type mice but not in Per1-/- Per2-/- mice, suggesting a functional clock-dependent nature of the micturition rhythm. Particularly in PDK mice, the water intake and urinary excretion displayed an arrhythmic pattern under constant darkness, and the amount of water consumed and excreted significantly increased compared with those of WT mice. These results suggest that local circadian clocks reside in three types of bladder tissue and the lumbar spinal cord and may have important roles in the circadian control of micturition function.
Animals ; *Circadian Clocks ; Drinking ; Mice ; Organ Specificity ; Periaqueductal Gray/metabolism/physiology ; Period Circadian Proteins/genetics/*metabolism ; Pons/metabolism/physiology ; Spinal Cord/*metabolism/physiology ; Urinary Bladder/innervation/metabolism/*physiology ; Urination