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*

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*

Sleep deprivation (SD) has many deleterious health effects and occurs in more than 70% of pregnant women. However, the changes in sex hormones and relevant mechanisms after SD have not been well clarified. The aim of the present study was to explore the effects of SD on the secretion of sex hormones and the underlying mechanisms. Twelve pregnant Wistar rats were divided into control (CON, n = 6) and SD (n = 6) groups. Pregnant rats in the SD group were deprived of sleep for 18 h, and allowed free rest for 6 h, and then the above procedures were repeated until delivery. The CON group lived in a 12 h light/dark light cycle environment. Estradiol (E2) and progesterone (P4) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of circadian clock genes, Bmal1, Clock and Per2, in hypothalamus and pituitary gland tissues were evaluated by immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The PI3K and Akt phosphorylation levels in the hypothalamic and pituitary tissues were determined by Western blot. The results showed that, compared with the CON group, the SD group exhibited significantly reduced serum E2 and P4 levels, down-regulated Bmal1, Clock and Per2 expression, as well as decreased phosphorylation levels of PI3K and Akt. But there was no significant difference of the total PI3K and Akt protein expression levels between the two groups. These results suggest that SD might affect the expression of the circadian clock genes in the hypothalamus and pituitary via PI3K/Akt pathway, and subsequently regulate the secretion of sex hormones in the pregnant rats, which hints the important roles of SD-induced changes of serum sex hormone levels in the pregnant rats.
ARNTL Transcription Factors/metabolism* ; Animals ; Circadian Clocks/physiology* ; Circadian Rhythm/genetics* ; Female ; Gene Expression Regulation/genetics* ; Gonadal Steroid Hormones/metabolism* ; Hypothalamus/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Pituitary Gland/metabolism* ; Pregnancy ; Progesterone ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Rats, Wistar ; Signal Transduction ; Sleep Deprivation/metabolism*

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 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

High level noise can damage cochlear hair cells, auditory nerve and synaptic connections between cochlear hair cells and auditory nerve, resulting in noise-induced hearing loss (NIHL). Recent studies have shown that animal cochleae have circadian rhythm, which makes them different in sensitivity to noise throughout the day. Cochlear circadian rhythm has a certain relationship with brain-derived neurotrophic factor and glucocorticoids, which affects the degree of hearing loss after exposure to noise. In this review, we summarize the research progress of the regulation of cochlear sensitivity to noise by circadian rhythm and prospect the future research direction.
Animals ; Auditory Threshold ; Circadian Rhythm ; Cochlea ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Hair Cells, Auditory ; Hearing Loss, Noise-Induced ; Noise/adverse effects*

Difference of chronotypes makes influence to cognitive performance of individuals in routine duties. In this paper, 55 subjects with different chronotypes were subjected to continuous sleep deprivation for 30 h by using the constant routine protocol, during which core body temperature was measured continuously, and subjective sleepiness self-rating and the performance of selective attention were measured hourly. The results showed that the phase difference of core body temperature has no significant difference, yet the amplitude and term difference among the three chronotypes are significant. There was an advance in phase between subjective sleepiness self-rating and core body temperature, and the self-rating sleepiness of evening type came the latest, and the self-rating sleepiness of morning type dissipated the fastest. The response time of selective attention showed a 2 h phase delay with subjective sleepiness self-rating. And the analysis of core body temperature showed that the later the chronotype was, the greater the phase delay was. The correct rate of selective attention of different chronotypes were inconsistent with delay of subjective sleepiness self-rating and core body temperature. We provide reference for industry, aviation, military, medical and other fields to make a more scientific scheduling/ shifting based on cognitive performance characteristics of different chronotypes.
Attention/physiology* ; Circadian Rhythm/physiology* ; Homeostasis ; Humans ; Sleep/physiology* ; Sleep Deprivation ; Sleepiness

The psychological distress of cancer patients seriously affects their therapeutic effects. Effective psychological rehabilitation of cancer patients significantly improves their survival chance and quality of life. Circadian rhythm results from adaptation to the environment during the organism's evolution. When the endogenous clock system is disrupted or the external environment is changed, the body and the environment are out of synchronization, and the circadian rhythm will be disrupted. Circadian rhythm disorder is a common phenomenon in cancer patients, and the changes of circadian rhythm are closely related to their psychological distress. Many studies believe that the circadian rhythm disorder of cancer patients may directly or indirectly affect their psychology through various mechanisms, and targeted intervention by regulating the circadian rhythm of patients may be an essential means to promote the psychological rehabilitation.
Humans ; Quality of Life ; Circadian Rhythm/physiology* ; Chronobiology Disorders ; Neoplasms

PURPOSE: Studies on the physiology of the transposed stomach as an esophageal substitute in the form of a gastric pull-up or a gastric tube in children are limited. We conducted a study of motility and the pH of gastric esophageal substitutes using manometry and 24-hour pH measurements in 10 such patients. METHODS: Manometry and 24 hour pH studies were performed on 10 children aged 24 to 55 months who had undergone gastric esophageal replacement. RESULTS: Six gastric tubes (4, isoperistaltic; 2, reverse gastric tubes) and 4 gastric pull-ups were studied. Two gastric tubes and 4 gastric pull-ups were transhiatal. Four gastric tubes were retrosternal. The mean of the lowest pH at the midpoint of the substitute was 4.0 (range, 2.8–5.0) and in the stomach remaining below the diaphragm was 3.3 (range, 1.9–4.2). In both types of substitute, the difference between the peak and the nadir pH recorded in the intra-thoracic and the sub-diaphragmatic portion of the stomach was statistically significant (p < 0.05), with the pH in the portion below the diaphragm being lower. The lowest pH values in the substitute and in the remnant stomach were noted mainly in the evening hours whereas the highest pH was noted mainly in the morning hours. All the cases showed a simultaneous rise in the intra-cavitatory pressure along the substitute while swallowing. CONCLUSION: The study suggested a normal gastric circadian rhythm in the gastric esophageal substitute. Mass contractions occurred in response to swallowing. The substitute may be able to effectively clear contents.
Child* ; Circadian Rhythm ; Deglutition ; Diaphragm ; Gastric Stump ; Humans ; Hydrogen-Ion Concentration* ; Manometry* ; Physiology ; Stomach

Circadian rhythm is a periodic and continuous change in physiological, behavioral, and mental characteristics that occurs in most organisms on the Earth, because the Earth rotates in a 24-hour cycle. The circadian system regulates daily rhythms of physiology and behavior, such as the sleep/wake cycle, body temperature, hormonal secretion, and mood. The influence of circadian rhythm is very powerful, but limited research has addressed its effects. However, many recent studies have shown that circadian dysregulation may play an important role in the pathogenesis of bipolar disorder. This review study examined current and noteworthy studies, including the authors' own works, and proposes a possible clinical application of bipolar disorder based on evidence that circadian rhythm dysregulation in bipolar disorder may be a key pathogenetic mechanism.
Bipolar Disorder* ; Body Temperature ; Chronobiology Disorders ; Circadian Rhythm* ; Physiology