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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic polyarticular pain, and its main pathological features include inflammatory cell infiltration, synovial fibroblast proliferation, and cartilage erosion. Immune cells, synovial cells and neuroendocrine factors play pivotal roles in the pathophysiological mechanism underlying rheumatoid arthritis. Biological clock genes regulate immune cell functions, which is linked to rhythmic changes in arthritis pathology. Additionally, the interaction between biological clock genes and neuroendocrine factors is also involved in rhythmic changes in rheumatoid arthritis. This review provides an overview of the contributions of circadian rhythm genes to RA pathology, including their interaction with the immune system and their involvement in regulating the secretion and function of neuroendocrine factors. A molecular understanding of the role of the circadian rhythm in RA may offer insights for effective disease management.

The synthesis and secretion of cortisol are controlled by the hypothalamic–pituitary–adrenal axis. Cortisol exhibits a proper 24-h circadian rhythm that affects the brain, the autonomic nervous system, the heart, and the vasculature that prepares the cardiovascular system for optimal function during these anticipated behavioral cycles. A literature search was conducted using databases such as Google Scholar, PubMed, and Scopus. Relevant search terms included “circadian rhythm and cardiovascular”, “cortisol”, “cortisol and acute coronary syndrome”, “cortisol and arrhythmias”, “cortisol and sudden cardiac death”, “cortisol and stroke”, and “cardioprotective agents”. A total of 120 articles were obtained on the basis of the above search. Lower levels of cortisol were seen at the beginning of sleep, while there was a rise towards the end of sleep, with the highest level reached at the moment the individual wakes up. In the present review, we discuss the role of 11β-hydroxysteroid dehydrogenase (11β-HSD1), which is a novel molecular target of interest for treating metabolic syndrome and type-2 diabetes mellitus. 11β-HSD1 is the major determinant of cortisol excess, and its inhibition alleviates metabolic abnormalities. The present review highlights the role of cortisol, which controls the circadian rhythm, and describes its effect on the cardiovascular system. The review provides a platform for future potential cardioprotective therapeutic agents.

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide for which there are no curative therapies. The major challenge in curing infection is eradicating or silencing the covalent closed circular DNA (cccDNA) form of the viral genome. The circadian factors BMAL1/CLOCK and REV-ERB are master regulators of the liver transcriptome and yet their role in HBV replication is unknown. We establish a circadian cycling liver cell-model and demonstrate that REV-ERB directly regulates NTCP-dependent hepatitis B and delta virus particle entry. Importantly, we show that pharmacological activation of REV-ERB inhibits HBV infection in vitro and in human liver chimeric mice. We uncover a role for BMAL1 to bind HBV genomes and increase viral promoter activity. Pharmacological inhibition of BMAL1 through REV-ERB ligands reduces pre-genomic RNA and de novo particle secretion. The presence of conserved E-box motifs among members of the Hepadnaviridae family highlight an evolutionarily conserved role for BMAL1 in regulating this family of small DNA viruses. The circadian factors BMAL1/CLOCK and REV-ERB are master regulators of the human liver transcriptome but their role in hepatitis B virus infection is largely unknown. Here, Zhuang et al. show that REV-ERB regulates hepatitis B virus entry and BMAL1 directly binds HBV DNA and activates viral genome transcription.

The biological clock system is an intrinsic timekeeping device that integrates internal physiology and external cues. Maintaining a healthy biological clock system is crucial for life. Disruptions to the body’s internal clock can lead to disturbances in the sleep-wake cycle and abnormalities in hormone regulation, blood pressure, heart rate, and other vital processes. Long-term disturbances have been linked to the development of various common major diseases, including cardiovascular diseases, metabolic disorders, tumors, neuropsychiatric conditions, and so on. External factors, such as the diurnal rhythm of light, have a significant impact on the body’s internal clock. Additionally, as an important non-photic zeitgeber, exercise can regulate the body’s internal rhythms to a certain extent, making it possible to become a non-drug intervention for preventing and treating circadian rhythm disorders. This comprehensive review encompasses behavioral, physiological, and molecular perspectives to provide a deeper understanding of how exercise influences circadian rhythms and its association with related diseases.

Biological clocks are genetically encoded oscillators that allow organisms to anticipate changes in the light–dark environment that are tied to the rotation of Earth. Clocks enhance fitness and growth in prokaryotes, and they are expressed throughout the central nervous system and peripheral tissues of multicelled organisms in which they influence sleep, arousal, feeding and metabolism. Biological clocks capture the imagination because of their tie to geophysical time, and tools are now in hand to analyse their function in health and disease at the cellular and molecular level.

Several electrical neural oscillatory abnormalities have been associated with schizophrenia, although the underlying mechanisms of these oscillatory problems are unclear. Animal studies suggest that one of the key mechanisms of neural oscillations is through glutamatergic regulation; therefore, neural oscillations may provide a valuable animal–clinical interface on studying glutamatergic dysfunction in schizophrenia. To identify glutamatergic control of neural oscillation relevant to human subjects, we studied the effects of ketamine, an N -methyl- D -aspartate antagonist that can mimic some clinical aspects of schizophrenia, on auditory-evoked neural oscillations using a paired-click paradigm. This was a double-blind, placebo-controlled, crossover study of ketamine vs saline infusion on 10 healthy subjects. Clinically, infusion of ketamine in subanesthetic dose significantly increased thought disorder, withdrawal–retardation, and dissociative symptoms. Ketamine significantly augmented high-frequency oscillations (gamma band at 40–85 Hz, p =0.006) and reduced low-frequency oscillations (delta band at 1–5 Hz, p <0.001) compared with placebo. Importantly, the combined effect of increased gamma and reduced delta frequency oscillations was significantly associated with more withdrawal–retardation symptoms experienced during ketamine administration ( p =0.02). Ketamine also reduced gating of the theta-alpha (5–12 Hz) range oscillation, an effect that mimics previously described deficits in schizophrenia patients and their first-degree relatives. In conclusion, acute ketamine appeared to mimic some aspects of neural oscillatory deficits in schizophrenia, and showed an opposite effect on scalp-recorded gamma vs low-frequency oscillations. These electrical oscillatory indexes of subanesthetic ketamine can be potentially used to cross-examine glutamatergic pharmacological effects in translational animal and human studies.

Circadian (daily) rhythms are present in almost all plants and animals. In mammals, a brain clock located in the hypothalamic suprachiasmatic nucleus maintains synchrony between environmental light/dark cycles and physiology and behavior. Over the past 100 y, especially with the advent of electric lighting, modern society has resulted in a round-the-clock lifestyle, in which natural connections between rest/activity cycles and environmental light/dark cycles have been degraded or even broken. Instances in which rapid changes to sleep patterns are necessary, such as transmeridian air travel, demonstrate negative effects of acute circadian disruption on physiology and behavior. However, the ramifications of chronic disruption of the circadian clock for mental and physical health are not yet fully understood. By housing mice in 20-h light/dark cycles, incongruous with their endogenous ~24-h circadian period, we were able to model the effects of chronic circadian disruption noninvasively. Housing in these conditions results in accelerated weight gain and obesity, as well as changes in metabolic hormones. In the brain, circadian-disrupted mice exhibit a loss of dendritic length and decreased complexity of neurons in the prelimbic prefrontal cortex, a brain region important in executive function and emotional control. Disrupted animals show decreases in cognitive flexibility and changes in emotionality consistent with the changes seen in neural architecture. How our findings translate to humans living and working in chronic circadian disruption is unknown, but we believe that this model can provide a foundation to understand how environmental disruption of circadian rhythms impacts the brain, behavior, and physiology.

Most processes within organisms, and most interactions between organisms and their environment, have distinct time profiles. The temporal coordination of such processes is crucial across levels of biological organization, but disciplines differ widely in their approaches to study timing. Such differences are accentuated between ecologists, who are centrally concerned with a holistic view of an organism in relation to its external environment, and chronobiologists, who emphasize internal timekeeping within an organism and the mechanisms of its adjustment to the environment. We argue that ecological and chronobiological perspectives are complementary, and that studies at the intersection will enable both fields to jointly overcome obstacles that currently hinder progress. However, to achieve this integration, we first have to cross some conceptual barriers, clarifying prohibitively inaccessible terminologies. We critically assess main assumptions and concepts in either field, as well as their common interests. Both approaches intersect in their need to understand the extent and regulation of temporal plasticity, and in the concept of ‘chronotype’, i.e. the characteristic temporal properties of individuals which are the targets of natural and sexual selection. We then highlight promising developments, point out open questions, acknowledge difficulties and propose directions for further integration of ecological and chronobiological perspectives through Wild Clock research. This article is part of the themed issue ‘Wild Clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals’.

Synchronizing rhythms of behaviour and metabolic processes is important for cardiovascular health and preventing metabolic diseases. The nuclear receptors REV-ERB-α and REV-ERB-β have an integral role in regulating the expression of core clock proteins driving rhythms in activity and metabolism. Here we describe the identification of potent synthetic REV-ERB agonists with in vivo activity. Administration of synthetic REV-ERB ligands alters circadian behaviour and the circadian pattern of core clock gene expression in the hypothalami of mice. The circadian pattern of expression of an array of metabolic genes in the liver, skeletal muscle and adipose tissue was also altered, resulting in increased energy expenditure. Treatment of diet-induced obese mice with a REV-ERB agonist decreased obesity by reducing fat mass and markedly improving dyslipidaemia and hyperglycaemia. These results indicate that synthetic REV-ERB ligands that pharmacologically target the circadian rhythm may be beneficial in the treatment of sleep disorders as well as metabolic diseases. Synthetic REV-ERB agonists can alter the circadian expression of core clock genes in the hypothalami of mice, which changes the expression of metabolic genes in liver, skeletal muscle and adipose tissue, and results in increased energy expenditure. Adjusting the metabolic clock Metabolic processes need to run like clockwork to prevent disease. Core clock proteins drive these rhythms, and the nuclear receptors REV-ERB-α and REV-ERB-β have a central role in regulating the expression of clock genes. Solt et al . report the identification of potent synthetic REV-ERB agonists, termed SR9011 and SR9009, which can alter the circadian expression of core clock genes in the hypothalami of mice. This is shown to alter the expression of metabolic genes in liver, skeletal-muscle and adipose tissue, and results in increased energy expenditure by the mice. The REV-ERB agonists reduce fat mass in diet-induced obese mice and improve dyslipidaemia and hyperglycaemia. These results suggest that synthetic REV-ERB ligands are promising candidates for the treatment of metabolic diseases. Cho et al . present genetic evidence that REV-ERB-α and REV-ERB-β are indispensible for the coordination of circadian rhythm and metabolism. Mice without REV-ERBs show disrupted expression of clock and lipid homeostatic gene networks. They have altered circadian wheel-running behaviour and deregulated lipid metabolism. These data ally REV-ERB-α and REV-ERB-β with PER, CRY and other components of the principal feedback loop that drives circadian expression.

The workers and employees in various institutions are subjected to different shifts and work schedules. The employees work not only at daytime but also during odd hours at night. The biological clock of an individual is often altered during night shifts. This affects the psychosocial well-being and circadian nutritional intake of the worker. Disturbance in circadian rhythm results in the development of metabolic disorders such as hypertension, dyslipidemia, dysglycemia, and abdominal obesity. In the present review, we discuss the nature of shift work, sleep/wake cycle of an individual, chrononutrition, dietary habits, and meal changes with regard to timing and frequency, related to shift work. We also discuss the relationship between nutritional intake and psychosocial well-being among shift workers. The review may be beneficial for prevention of metabolic disorders and maintaining sound psychological condition in shift workers.