Abstract

Most living organisms in both the plant and animal kingdoms have evolved processes to stay in tune with the alternation of day and night, and to optimize their physiology as a function of light supply. In mammals, a circadian clock relying on feedback loops between key transcription factors will thus control the temporally regulated pattern of expression of most genes. Modern ways of life have highly altered the synchronization of human activities with their circadian clocks. This review discusses the links between an altered circadian clock and the rise of pathologies. We then sum up the proofs of concept advocating for the integration of circadian clock considerations in chronotherapy for health care, medicine, and pharmacotherapy. Finally, we discuss the current challenges that circadian biology must face and the tools to address them.

https://www.mdpi.com/1999-4923/14/7/1424

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Abstract

From bacteria to mammals, nearly all organisms have adapted their physiology and behavior to a daily rhythm. These circadian (daily) rhythms influence virtually all aspects of physiological architecture (i.e., from gene expression to organismal behavior). Therefore, it is not surprising that several features of the immune response are regulated in a time-of-day dependent manner. The field of chrono-immunology has expanded tremendously over the past decade. In this abridged review, we present studies from the past five years that have revealed new parameters of the immune system that demonstrate daily variations in the control of pathogens and response to microbial components. These studies analyzed how the disruption of circadian rhythms impairs immune function, how microbial components alter the circadian clock, and how immune responses demonstrate daily variations in human subjects. Further elucidating the intricate connections between the circadian clock and the immune system will hopefully provide opportunities for chrono-immunotherapy in disease treatment and prevention.

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6585517/

The post Time is on the Immune System’s Side, Yes it is appeared first on EMFSA.

Date: November 24, 2021

Source: RCSI

Summary: New research has demonstrated the significant role that an irregular body clock plays in driving inflammation in the body’s immune cells, with implications for the most serious and prevalent diseases in humans.

Snippet:

Dr George Timmons, lead author on the study, said: “Our results add to the growing body of work showing why disruption of our body clock leads to inflammatory and infectious disease, and one of the aspects is fuel usage at the level of key immune cells such as macrophages.”

Dr Annie Curtis, Senior Lecturer at RCSI School of Pharmacy and Biomolecular Sciences and senior author on the paper, added: “This study also shows that anything which negatively impacts on our body clocks, such as insufficient sleep and not enough daylight, can impact on the ability of our immune system to work effectively.”

Journal Reference:

1. George A. Timmons, Richard G. Carroll, James R. O’Siorain, Mariana P. Cervantes-Silva, Lauren E. Fagan, Shannon L. Cox, Eva Palsson-McDermott, David K. Finlay, Emma E. Vincent, Nicholas Jones, Annie M. Curtis. The Circadian Clock Protein BMAL1 Acts as a Metabolic Sensor In Macrophages to Control the Production of Pro IL-1β. Frontiers in Immunology, 2021; 12 DOI: 10.3389/fimmu.2021.700431

https://www.sciencedaily.com/releases/2021/11/211124154033.htm

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Highlights

Although circadian rhythm disruption (CRD) was typically considered to be a risk for chronic diseases solely for shift workers (∼20% of workforce), new epidemiological data suggest more than 80% of the population may be living a shift work lifestyle and thus are at elevated risk for chronic diseases.

Acute CRD compromises health with temporary physical challenges and may be a trigger for underlying latent diseases. Chronic CRD raises the risk for cancer along with a range of diseases affecting the central nervous system, immune and reproductive systems, metabolic organs, endocrine functions, and cardiovascular health.

Recent progress in understanding the molecular mechanisms of circadian timing and diurnal rhythms of tissue-specific gene products has generated testable hypotheses for how the circadian timing system optimizes health and, conversely, how circadian disruption leads to diseases.

Leveraging circadian rhythms to prevent, manage, and treat diseases involves three major strategies: optimizing the circadian lifestyle (‘training the clock’), optimizing timing of therapies (‘clocking the drugs’), and targeting specific circadian clock components (‘drugging the clock’).

Daily rhythms in behavior, physiology, and metabolism are an integral part of homeostasis. These rhythms emerge from interactions between endogenous circadian clocks and ambient light-dark cycles, sleep-activity cycles, and eating-fasting cycles. Nearly the entire primate genome shows daily rhythms in expression in tissue- and locus-specific manners. These molecular rhythms modulate several key aspects of cellular and tissue function with profound implications in public health, disease prevention, and disease management. In modern societies light at night disrupts circadian rhythms, leading to further disruption of sleep-activity and eating-fasting cycles. While acute circadian disruption may cause transient discomfort or exacerbate chronic diseases, chronic circadian disruption can enhance risks for numerous diseases. The molecular understanding of circadian rhythms is opening new therapeutic frontiers placing the circadian clock in a central role. Here, we review recent advancements on how to enhance our circadian clock through behavioral interventions, timing of drug administration, and pharmacological targeting of circadian clock components that are already providing new preventive and therapeutic strategies for several diseases, including metabolic syndrome and cancer.

https://www.sciencedirect.com/science/article/abs/pii/S0165614718301196

© 2018 Elsevier Ltd. All rights reserved.

The post Training the Circadian Clock, Clocking the Drugs, and Drugging the Clock to Prevent, Manage, and Treat Chronic Diseases appeared first on EMFSA.

Abstract

Increasing evidences suggest the involvement of disrupted circadian clock in various pathologies including stroke and substance abuse. Here we took an attempt to do a comparative study on the regulation of circadian clock gene expression under two pathological circumstances – Opioid addiction and Ischemic stroke in the same cell line model (human neuroblastoma SH-SY5Y cells). To mimic in vivo ischemic stroke condition cells were placed in a hypoxia chamber and incubated for 10 h in balanced salt solution lacking glucose, aerated with an anaerobic gas mixture (95% N₂ and 5% C0₂). For opioid addiction cells were treated with morphine sulphate at 10 μM dose for 48 h. We found that although circadian clock gets disturbed in both states, pattern of alteration of clock gene expressions were different and change was more severe in ischemic stroke than addiction. Interestingly, increase in expression of Cry1 showed as a common factor to both the diseases. This paper also emphasizes the interconnection between the severities of neuronal injury induced by ischemic stroke or opioid abuse to circadian system. Finally, this study will further enrich our knowledge towards the pattern of circadian rhythm disturbances under different pathological states.

https://pubmed.ncbi.nlm.nih.gov/33894675/

Copyright © 2021 Elsevier Inc. All rights reserved.

The post Increase of Cry 1 expression is a common phenomenon of the disturbed circadian clock in ischemic stroke and opioid addiction appeared first on EMFSA.

Abstract

Purpose: Circadian clock is synchronized to the 24-hour day by the daily light-dark cycle and proper function of circadian rhythm is essential for many physiological processes. Disruption of circadian rhythm can affect disease processes and influence disease severity, treatment responses, and even survivorship. In this retrospective case-controlled study, we tried to explore whether expression of circadian clock genes was disturbed in patients with bronchial asthma.

Patients and methods: We performed real-time quantitative reverse transcriptase-polymerase chain reactions to examine the expression of the nine core circadian clock genes (BMAL1, CK1ε, CLOCK, CRY1, CRY2, PER1, PER2, PER3, and TIM) in total leukocytes of peripheral blood collected at chest clinics from 120 patients with asthma and 60 health individuals.

Results: Expression levels of the nine circadian clock genes were significantly different between patients and healthy individuals, but not associated with the asthma control status. We also noted the difference of PER3 expression in asthmatic patients with and without nocturnal symptoms. In well-controlled asthmatics, expression of BMAL1, CK1ε, CLOCK, CRY1, CRY2, and PER1 was significantly lower in patients with nocturnal symptoms than those without nocturnal symptoms. However, in not well-controlled asthmatics, expression of only BMAL1, CK1ε, PER1, and PER2 was significantly different between patients with and without nocturnal symptoms. Binary logistic regression analysis selected BMAL1, CKIε, PER3, and TIM as independent factors for bronchial asthma and ROC curves showed the combined expression of these four genes enhanced the capability of predicting asthma (AUC=0.924; 95% CI=0.875-0.958; P<0.001).

Conclusion: Our results showed altered expression of circadian clock genes in patients with bronchial asthma and down-regulated PER3 in patients with nocturnal symptoms. Altered expression of circadian clock genes was also observed in asthmatics with or without nocturnal symptoms in well- or not well-controlled subgroups. Combined expression of BMAL1, CKIε, PER3, and TIM could be a potential predictor for bronchial asthma.

https://pubmed.ncbi.nlm.nih.gov/33888995/

© 2021 Chen et al.

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by University of Waterloo

https://medicalxpress.com/news/2021-04-shift-work-negative-impacts-health-affects.html

Shift-work and irregular work schedules can cause several health-related issues and affect our defense against infection, according to new research from the University of Waterloo.

These health-related issues occur because the body’s natural clock, called the circadian clock, can be disrupted by inconsistent changes in the sleep-wake schedule and feeding patterns often caused by shift work. To study this, researchers at Waterloo developed a mathematical model to look at how a disruption in the circadian clock affects the immune system in fighting off illness.

“Because our immune system is affected by the circadian clock, our ability to mount an immune response changes during the day,” said Anita Layton, professor of Applied Mathematics, Computer Science, Pharmacy and Biology at Waterloo. “How likely are you to fight off an infection that occurs in the morning than midday? The answer depends on whether you are a man or a woman, and whether you are among quarter of the modern-day labor force that has an irregular work schedule.”

Read more at: https://medicalxpress.com/news/2021-04-shift-work-negative-impacts-health-affects.html

The post Shift-work causes negative impacts on health, affects men and women differently appeared first on EMFSA.

Abstract

Molecular clocks help organisms to adapt important physiological functions to periodically changing conditions in the environment. These include the adaption of the 24 h sleep-wake rhythm to changes of day and night. The circadian clock is known to act as a key regulator in processes of health and disease in different organs. The knowledge on the circadian clock led to the development of chronopharmacology and chronotherapy. These fields aim to investigate how efficiency of medication and therapies can be improved based on circadian clock mechanisms. In this review we aim to highlight the role of the circadian clock in oral tissues and its potential in the different fields of dentistry including oral and maxillofacial surgery, restorative dentistry, endodontics, periodontics and orthodontics to trigger the evolving field of chronodentistry.

https://bmcoralhealth.biomedcentral.com/articles/10.1186/s12903-019-0720-x

The post Chronodentistry: the role & potential of molecular clocks in oral medicine appeared first on EMFSA.

Abstract

The circadian clock exerts an important role in systemic homeostasis as it acts a keeper of time for the organism. The synchrony between the daily challenges imposed by the environment needs to be aligned with biological processes and with the internal circadian clock. In this review, it is provided an in-depth view of the molecular functioning of the circadian molecular clock, how this system is organized, and how central and peripheral clocks communicate with each other. In this sense, we provide an overview of the neuro-hormonal factors controlled by the central clock and how they affect peripheral tissues. We also evaluate signals released by peripheral organs and their effects in the central clock and other brain areas. Additionally, we evaluate a possible communication between peripheral tissues as a novel layer of circadian organization by reviewing recent studies in the literature. In the last section, we analyze how the circadian clock can modulate intracellular and tissue-dependent processes of metabolic organs. Taken altogether, the goal of this review is to provide a systemic and integrative view of the molecular clock function and organization with an emphasis in metabolic tissues.

Conclusions

The circadian clock system is a complex and pervasive network that directly or indirectly controls a significant portion of all biological processes. Its role as a systemic regulator is seen in experimental models of gene silencing or knockout. Advancements in tissue-specific clock gene modulation has been important for a better understanding of tissue clock gene organization at both cellular as well as systemic levels. In addition to its molecular basis, the organizational aspects of the circadian clock network have received increased attention over the last years. Understanding how this biological timing machinery works at all levels of organization will be important to fully assess the consequences of circadian rhythm disruption by modern lifestyles and devise ways to prevent chronodisruption and treat associated diseases and conditions.

https://link.springer.com/article/10.1007/s00018-021-03800-2

The post The circadian clock and metabolic homeostasis: entangled networks appeared first on EMFSA.

Abstract

We currently find ourselves in the midst of a global coronavirus disease 2019 (COVID-19) pandemic, caused by the highly infectious novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we discuss aspects of SARS-CoV-2 biology and pathology and how these might interact with the circadian clock of the host. We further focus on the severe manifestation of the illness, leading to hospitalization in an intensive care unit. The most common severe complications of COVID-19 relate to clock-regulated human physiology. We speculate on how the pandemic might be used to gain insights on the circadian clock but, more importantly, on how knowledge of the circadian clock might be used to mitigate the disease expression and the clinical course of COVID-19.

https://pubmed.ncbi.nlm.nih.gov/33573430/

The post A Timely Call to Arms: COVID-19, the Circadian Clock, and Critical Care appeared first on EMFSA.