scholarly journals REVIEW OF RESEARCH ON THE RELATIONSHIP BETWEEN CIRCADIAN RHYTHMS AND CARCINOGENESIS USING ANIMAL MODELS

2021 ◽  
Vol 20 (3) ◽  
pp. 134-143
Author(s):  
G. S. Kireeva ◽  
E. A. Gubareva ◽  
M. A. Maydin ◽  
A. V. Panchenko ◽  
M. L. Tyndyk ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Animal Models ◽  
Clock Gene ◽  
Clock Genes ◽  
Tumor Development ◽  
Malignant Neoplasms ◽  
Light Cycle ◽  
Gene System ◽  
The Relationship

Purpose of the study: to review in vivo studies on the relationship and role of various molecular genetic components of the circadian rhythm system in the initiation and development of malignant neoplasms. in contrast to clinical and epidemiological studies, animal models, including transgenic animal models, can model various changes and disturbances in the activity of clock genes and track the results of these changes.Material and Methods. the review includes data from studies carried out over the past 10 years in animal models, studying the mechanisms and effects of disturbances in the system of circadian rhythms related to the formation and development of tumors. the data sources for the review were the Medline, embase and scopus databases.Results. analysis of the literature has shown that interference with the work of the «biological clock» by changing the light cycle, disrupting the expression of clock genes and other manipulations is a factor predisposing to the development of tumors. in tumors of various types, the expression of clock genes is often mismatched, and it is unclear at what stage of their formation this occurs. in addition, the development of tumors disrupts the circadian homeostasis of the body. there are three key areas of research aimed at studying the role of circadian rhythms in tumor development: disturbance of circadian rhythms as a carcinogenic factor, disturbances in the clock gene system in a tumor, disturbances in the clock gene system of the whole organism, provoked by tumor development.Conclusion. the results of studies on animal models demonstrate that the relationship between the disturbance of circadian rhythms and the tumor process is complex since the causal relationship has not yet been studied. in this regard, the prospect of targeted pharmacological correction of circadian rhythms in clinical practice in cancer patients does not seem to be the nearest one.

scholarly journals Circadian Rhythms in Bacterial Sepsis Pathology: What We Know and What We Should Know

2021 ◽  
Vol 11 ◽  
Author(s):  
Malena Lis Mul Fedele ◽  
Camila Agustina Senna ◽  
Ignacio Aiello ◽  
Diego Andres Golombek ◽  
Natalia Paladino
Keyword(s):  
Circadian Rhythms ◽  
Animal Models ◽  
Clock Gene ◽  
Circadian System ◽  
Main Role ◽  
Bacterial Sepsis ◽  
Hypothermic Response ◽  
Sepsis Induction ◽  
Improve Patient

Sepsis is a syndrome caused by a deregulated host response to infection, representing the primary cause of death from infection. In animal models, the mortality rate is strongly dependent on the time of sepsis induction, suggesting a main role of the circadian system. In patients undergoing sepsis, deregulated circadian rhythms have also been reported. Here we review data related to the timing of sepsis induction to further understand the different outcomes observed both in patients and in animal models. The magnitude of immune activation as well as the hypothermic response correlated with the time of the worst prognosis. The different outcomes seem to be dependent on the expression of the clock gene Bmal1 in the liver and in myeloid immune cells. The understanding of the role of the circadian system in sepsis pathology could be an important tool to improve patient therapies.

Dormancy, Diapause, and the Role of the Circadian System in Insect Photoperiodism

2020 ◽  
Vol 65 (1) ◽  
pp. 373-389 ◽  
Author(s):  
David S. Saunders
Keyword(s):  
Clock Genes ◽  
Animal Experiments ◽  
Transcript Abundance ◽  
Circadian System ◽  
Gene Transcript ◽  
Light Cycle ◽  
Peripheral Oscillators ◽  
Circadian Clock Genes ◽  
Similar Phase

Whole-animal experiments devised to investigate possible association between photoperiodic time measurement and the circadian system (Bünning's hypothesis) are compared with more recent molecular investigations of circadian clock genes. In Sarcophaga argyrostoma and some other species, experimental cycles of light and darkness revealed a photoperiodic oscillator, set to constant phase at dusk and measuring night length repeatedly during extended periods of darkness. In some species, however, extreme dampening revealed an unrepetitive (i.e., hourglass-like) response. Rhythms of clock gene transcript abundance may also show similar phase relationships to the light cycle, and gene silencing of important clock genes indicates that they play a crucial role in photoperiodism either alone or in concert. However, the multiplicity of peripheral oscillators in the insect circadian system indicates that more complex mechanisms might also be important.

scholarly journals Biological mechanisms linked to inflammation in cancer: Discovery of tumor microenvironment-related biomarkers and their clinical application in solid tumors

2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 8-11 ◽  
Author(s):  
Paola Nisticò ◽  
Gennaro Ciliberto
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Tumor Development ◽  
Short Paper ◽  
Great Relevance ◽  
Cellular Components ◽  
The Relationship

Our view of cancer biology radically shifted from a “cancer-cell-centric” vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved.

scholarly journals Rhythmic Messenger Ribonucleic Acid Expression of Clock Genes and Adipocytokines in Mouse Visceral Adipose Tissue

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5631-5636 ◽  
Author(s):  
Hitoshi Ando ◽  
Hayato Yanagihara ◽  
Yohei Hayashi ◽  
Yuri Obi ◽  
Shuichi Tsuruoka ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Clock Gene ◽  
Clock Genes ◽  
Adipose Tissues ◽  
Peripheral Tissues ◽  
Rhythmic Expression ◽  
Gene System ◽  
Visceral Adipose ◽  
Ay Mice

Various peripheral tissues show circadian rhythmicity, which is generated at the cellular level by their own core oscillators that are composed of transcriptional/translational feedback loops involving a set of clock genes. Although the circulating levels of some adipocytokines, i.e. bioactive substances secreted by adipocytes, are on a 24-h rhythmic cycle, it remains to be elucidated whether the clock gene system works in adipose tissue. To address this issue, we investigated the daily mRNA expression profiles of the clock genes and adipocytokines in mouse perigonadal adipose tissues. In C57BL/6J mice, all transcript levels of the clock genes (Bmal1, Per1, Per2, Cry1, Cry2, and Dbp) and adipocytokines (adiponectin, resistin, and visfatin) clearly showed 24-h rhythms. On the other hand, the rhythmic expression of these genes was mildly attenuated in obese KK mice and greatly attenuated in more obese, diabetic KK-Ay mice. Obese diabetes also diminished the rhythmic expression of the clock genes in the liver. Interestingly, a 2-wk treatment of KK and KK-Ay mice with pioglitazone impaired the 24-h rhythmicity of the mRNA expression of the clock genes and adipocytokines despite the antidiabetic effect of the drug. In contrast, pioglitazone improved the attenuated rhythmicity in the liver. These findings suggest that the intracellular clock gene system acts in visceral adipose tissues as well as liver and is influenced by the conditions of obesity/type 2 diabetes and pioglitazone treatment.

scholarly journals An Overview of the Role of Mechanical Stretching in the Progression of Lung Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Fengying Gong ◽  
Yuchao Yang ◽  
Liangtao Wen ◽  
Congrong Wang ◽  
Jingjun Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Mechanical Load ◽  
Tumor Development ◽  
Physical Factors ◽  
Mechanical Factors ◽  
Tissue Characteristics ◽  
The Relationship ◽  
Mechanical Stretching

Cells and tissues in the human body are subjected to mechanical forces of varying degrees, such as tension or pressure. During tumorigenesis, physical factors, especially mechanical factors, are involved in tumor development. As lung tissue is influenced by movements associated with breathing, it is constantly subjected to cyclical stretching and retraction; therefore, lung cancer cells and lung cancer-associated fibroblasts (CAFs) are constantly exposed to mechanical load. Thus, to better explore the mechanisms involved in lung cancer progression, it is necessary to consider factors involved in cell mechanics, which may provide a more comprehensive analysis of tumorigenesis. The purpose of this review is: 1) to provide an overview of the anatomy and tissue characteristics of the lung and the presence of mechanical stimulation; 2) to summarize the role of mechanical stretching in the progression of lung cancer; and 3) to describe the relationship between mechanical stretching and the lung cancer microenvironment, especially CAFs.

Suprachiasmatic Nucleus Anatomy, Physiology, and Neurochemistry

2018 ◽  
Author(s):  
Rae Silver
Keyword(s):  
Gene Expression ◽  
Circadian Rhythms ◽  
Electrical Activity ◽  
Suprachiasmatic Nucleus ◽  
Clock Gene ◽  
Clock Genes ◽  
Transgenic Animals ◽  
The Body ◽  
Network Activity ◽  
Over Time

We live in an approximately 24-hour world and circadian rhythms have evolved to adapt organisms to the opportunities presented by Earth’s 24-hour cycle of light and dark. A “master clock” located in the suprachiasmatic nucleus (SCN) of the brain orchestrates daily rhythms in all manner of behavioral, endocrine, metabolic, autonomic, and homeostatic systems in our bodies. The SCN is comprised of about 20,000 neurons and about one third as many astroglia. How can so few neurons and astroglia guide so many rhythms? How do neurons time out an interval as long as a day? The answers are a case study in understanding how genes within cells, and cells within circuits, function together to perform complex activities and optimize bodily functions. While individual clock cells are found in virtually all bodily tissues, the unique connectome of the SCN, its specialized afferent inputs from the retinohypothalamic tract, and its neural and humoral outputs enable its “babel” of neuronal types to synchronize their activity and signal time to the rest of the body. At the molecular-cellular level, circadian rhythms are regulated by a 24-hour transcriptional–translational feedback loop. At the SCN tissue level, individual SCN neurons coordinate their gene expression and electrical activity, working together in circuits that sustain coherent rhythms. The SCN has many distinct cell types based on their neurotransmitters, neuropeptides, and afferent and efferent connections. There has been much progress in unraveling the dynamic network organization that underlies the SCN network’s communications. Though the precise anatomical connections underlying interneuronal communication in the SCN are not completely understood, key signaling mechanisms that sustain the SCN’s intrinsic rhythmicity have been tackled using intersectional genomic tools. Transgenic animals that permit the visualization of clock gene–protein expression have enabled analysis of SCN network activity over time. Availability of animals bearing mutations in clock genes or proteins enable the determination of changes within neurons, among neurons in networks, and their impact on behavior. The use of continuous readouts of circadian activity that track behavior, or clock gene expression, or electrical activity changes over time, within an SCN or a single neuron, leads the way to unraveling mechanisms sustaining the circadian timing system. Because the results of circadian studies generate huge amounts of data, the entry of mathematical modelers and statisticians into the field has begun to yield useful and testable predictions on how these multiplexed systems work to adapt to our 24-hour world.

scholarly journals Diurnal Amplitudes of Arterial Pressure and Heart Rate Are Dampened in Clock Mutant Mice and Adrenalectomized Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3576-3580 ◽  
Author(s):  
Hiroyoshi Sei ◽  
Katsutaka Oishi ◽  
Sachiko Chikahisa ◽  
Kazuyoshi Kitaoka ◽  
Eiji Takeda ◽  
...  
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Clock Gene ◽  
Clock Genes ◽  
Plasma Aldosterone ◽  
Mutant Mice ◽  
Wild Type ◽  
Clock Mutant ◽  
Wild Type Control

Arterial pressure (AP), heart rate (HR), and cardiovascular diseases, including ischemic heart attack and cerebrovascular accident, show diurnal variation. Evidence that circadian-related genes contribute to cardiovascular control has been accumulated. In this study, we measured the AP and HR of Clock mutant mice on the Jcl/ICR background to determine the role of the Clock gene in cardiovascular function. Mice with mutated Clock genes had a dampened diurnal rhythm of AP and HR, compared with wild-type control mice, and this difference disappeared after adrenalectomy. The diurnal acrophase in both mean arterial pressure and HR was delayed significantly in Clock mutant mice, compared with wild-type mice, and this difference remained after adrenalectomy. Clock mutant mice had a lower concentration of plasma aldosterone, compared with wild-type mice. Our data suggest that the adrenal gland is involved in the diurnal amplitude, but not the acrophase, of AP and HR, and that the function of the Clock gene may be related to the nondipping type of AP elevation.

scholarly journals Role of cardiotrophin‐1 in the regulation of metabolic circadian rhythms and adipose core clock genes in mice and characterization of 24‐h circulating CT‐1 profiles in normal‐weight and overweight/obese subjects

2017 ◽  
Vol 31 (4) ◽  
pp. 1639-1649 ◽  
Author(s):  
Miguel Lópeź‐Yoldi ◽  
Kimber L. Stanhope ◽  
Marta Garaulet ◽  
X. Guoxia Chen ◽  
Beatriz Marcos‐Gómeź ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Clock Genes ◽  
Normal Weight ◽  
Obese Subjects

scholarly journals Deletion of the Clock Gene Period2 (Per2) in Glial Cells Alters Mood-Related Behavior in Mice

2020 ◽  
Author(s):  
Tomaz Martini ◽  
Jürgen A. Ripperger ◽  
Jimmy Stalin ◽  
Andrej Kores ◽  
Michael Stumpe ◽  
...  
Keyword(s):  
Glial Cells ◽  
Clock Gene ◽  
Clock Genes ◽  
Specific Expression ◽  
Adeno Associated Virus ◽  
Resistant Phenotype ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Physiological Pathways

AbstractThe circadian clock regulates many biochemical and physiological pathways, and lack of clock genes, such as Period (Per) 2, do not only affect circadian activity rhythms, but can also modulate food-anticipatory and mood-related behaviors. However, it is not known how cell-type specific expression of Per2 contributes to these behaviors. In this study, we find that Per2 in glial cells is important for balancing mood-related behaviors. Genetic and adeno-associated virus-mediated deletion of Per2 in glial cells of mice leads to a depression-resistant phenotype, as manifested in reduced despair and anxiety. This is paralleled by an increase of the GABA transporter 3 (Gat3) mRNA and a reduction of glutamate levels in the nucleus accumbens (NAc). Exclusive deletion of Per2 in glia of the NAc reduced despair, but had no influence on anxiety. Our data provide strong evidence for an important role of glial Per2 in regulating mood-related behavior.

scholarly journals Machine Learning and In-Vivo Expression Analyses Reveal Circadian Clock Features Predictive of Anxiety in Humans

2021 ◽  
Author(s):  
Aziz Zafar ◽  
Rebeccah Overton ◽  
Ziad Attia ◽  
Ahmet Ay ◽  
Krista Ingram
Keyword(s):  
Machine Learning ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Clock Gene ◽  
Molecular Mechanisms ◽  
Clock Genes ◽  
Anxiety Symptoms ◽  
Circadian Phase ◽  
Functional Studies

Abstract Mood disorders, including anxiety, are associated with disruptions in circadian rhythms and are linked to polymorphisms in circadian clock genes. Molecular mechanisms underlying these connections may be direct—via transcriptional activity of clock genes on downstream mood pathways in the brain, or indirect—via clock gene influences on the phase and amplitude of circadian rhythms which, in turn, modulate physiological processes influencing mood. Employing machine learning combined with statistical approaches, we explored clock genotype combinations that predict risk for anxiety symptoms in a deeply phenotyped population. We identified multiple novel circadian genotypes predictive of anxiety, with the PER3B-AG/CRY1-CG genotype being the strongest predictor of anxiety risk in males. Molecular chronotyping, using clock gene expression oscillations, revealed that advanced circadian phase and robust circadian amplitudes are associated with high levels of anxiety symptoms. Further analyses revealed that individuals with advanced phases and pronounced circadian misalignment were at higher risk for severe anxiety symptoms. Our results support both direct and indirect influences of clock gene variants on mood: while sex-specific clock genotype combinations predictive of anxiety symptoms suggest direct effects on mood pathways, the mediation of PER3B effects on anxiety via diurnal preference measures and the association of circadian phase with anxiety symptoms provide evidence for indirect effects of the molecular clockwork on mood. Unraveling the complex molecular mechanisms underlying the links between circadian physiology and mood is essential to identifying the core clock genes to target in future functional studies, thereby advancing the development of non-invasive treatments for anxiety-related disorders.

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