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Makrinioti H, Chun S. Circadian clock gene expression: a key player in inflammation underlying chronic lung disease? ERJ Open Res 2025; 11:01066-2024. [PMID: 40337334 PMCID: PMC12053736 DOI: 10.1183/23120541.01066-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 10/19/2024] [Indexed: 05/09/2025] Open
Abstract
The circadian clock genes might play a key role in regulating the pathophysiological processes underlying COPD. Their role in regulating pathophysiological processes in other chronic lung diseases is still unclear, but important to elucidate. https://bit.ly/4f3KXQk.
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Affiliation(s)
- Heidi Makrinioti
- Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Sung Chun
- Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
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Chen Q, Wang W, Fang W, Qin L, Wang J, Huang X, Pan S, Zheng R. Generation of Myeloid-Specific Bmal1 Knockout Mice and Identification of Bmal1-Regulated Ferroptosis in Macrophages. Genesis 2025; 63:e70014. [PMID: 40197722 DOI: 10.1002/dvg.70014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 03/21/2025] [Accepted: 03/26/2025] [Indexed: 04/10/2025]
Abstract
Circadian clocks have a fundamental role in many physiological processes. Bmal1 (basic helix-loop-helix ARNT like 1) is a central master circadian clock gene. The global Bmal1 knockout mice were shown to have a loss of circadian rhythms, acceleration of aging, and shortened life span. However, global Bmal1 knockout mice did not exactly reflect the Bmal1 function in specific cell or tissue types. To address the importance of circadian rhythms in macrophages, we generated myeloid-specific Bmal1 knockout mice. The efficacy of Bmal1 gene deletion in macrophages was identified at DNA, transcription, protein levels, and function. In contrast to global Bmal1 knockout mice, Bmal1flox/flox and Bmal1mye-/- mice did not exhibit aging phenotypes. However, the deletion of Bmal1 resulted in a loss of rhythmic expression of the circadian genes in macrophages. RNA-Seq revealed that Bmal1 regulated the expression of cell death-related genes in macrophages. Furthermore, these genes have been identified as clock-controlled genes in rhythmic cell models, and Bmal1 controlled the rhythmic expression of these genes in macrophages. Finally, Bmal1 inhibited RSL3-induced ferroptosis in macrophages through Phgdh. In summary, the model of myeloid-specific Bmal1 knockout mice was successfully constructed, providing a tool for the study of the roles of Bmal1 in macrophages and the peripheral circadian clock. Meanwhile, Bmal1 regulates ferroptosis in macrophages.
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Affiliation(s)
- Qing Chen
- The Key Laboratory of Environmental Pollution Monitoring and Disease Control, School of Public Health, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, China
- Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wenyi Wang
- The Key Laboratory of Environmental Pollution Monitoring and Disease Control, School of Public Health, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, China
- Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Weijun Fang
- Department of Microbiology and Immunology, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Lianhua Qin
- Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jie Wang
- Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiaochen Huang
- Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Sha Pan
- The Key Laboratory of Environmental Pollution Monitoring and Disease Control, School of Public Health, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, China
| | - Ruijuan Zheng
- The Key Laboratory of Environmental Pollution Monitoring and Disease Control, School of Public Health, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, China
- Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
- Key Laboratory of Pathogen-Host Interaction, Ministry of Education, Department of Microbiology and Immunology, Tongji University School of Medicine, Shanghai, China
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Icedo-Nuñez S, Luna-Ramirez RI, Enns RM, Speidel SE, Hernández J, Zeng X, Sánchez-Castro MA, Aguilar-Trejo CM, Luna-Nevárez G, López-González MC, Reyna-Granados JR, Luna-Nevárez P. Validation of Polymorphisms Associated with the Immune Response After Vaccination Against Porcine Reproductive and Respiratory Syndrome Virus in Yorkshire Gilts. Vet Sci 2025; 12:295. [PMID: 40284797 PMCID: PMC12031381 DOI: 10.3390/vetsci12040295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 03/17/2025] [Accepted: 03/18/2025] [Indexed: 04/29/2025] Open
Abstract
Porcine respiratory and reproductive syndrome is a viral disease that impacts the health and profitability of swine farms, largely due to significant variation in the vaccination response. The objective was to identify and validate molecular markers associated with the antibody response in gilts following vaccination against the PRRSV. The study included one hundred (n = 100) 6-month-old Yorkshire gilts that were negative for the PRRSV. Gilts were randomly assigned to one of two treatments, PRRS-vaccinated (n = 75) and control (n = 25) groups. Blood samples collected on day 21 were analyzed to evaluate the antibody response, as indicated by the sample-to-positive (S/P) ratio, to the PRRSV following vaccination. DNA was extracted and genotyped using a low-density chip containing 10,000 single nucleotide polymorphisms (SNPs). A genome-wide association study (GWAS) was conducted to identify candidate SNPs associated with the S/P ratio, which were validated in two independent gilt populations (n = 226). The SNPs rs707264998, rs708860811, and rs81358818 in the genes RNF144B, XKR9, and BMAL1, respectively, were significantly associated (p < 0.01) with the S/P ratio and demonstrated an additive effect. In conclusion, three SNPs are proposed as candidate markers for an enhanced immune response to vaccination against the PRRSV and may be beneficial in genetic selection programs.
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Affiliation(s)
- Salvador Icedo-Nuñez
- Departamento de Ciencias Agronómicas y Veterinarias, Instituto Tecnológico de Sonora, Ciudad Obregón 85000, Mexico
| | - Rosa I. Luna-Ramirez
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85721, USA
| | - R. Mark Enns
- Department of Animal Sciences, Colorado State University, Fort Collins, CO 80523, USA
| | - Scott E. Speidel
- Department of Animal Sciences, Colorado State University, Fort Collins, CO 80523, USA
| | - Jesús Hernández
- Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo A.C., Hermosillo 83304, Mexico
| | - Xi Zeng
- Zoetis Inc., VMRD Genetics R&D, Kalamazoo, MI 49007, USA
| | | | - Carlos M. Aguilar-Trejo
- Departamento de Ciencias Agronómicas y Veterinarias, Instituto Tecnológico de Sonora, Ciudad Obregón 85000, Mexico
| | - Guillermo Luna-Nevárez
- Departamento de Ciencias Agronómicas y Veterinarias, Instituto Tecnológico de Sonora, Ciudad Obregón 85000, Mexico
| | - Martha C. López-González
- Departamento de Ciencias Agronómicas y Veterinarias, Instituto Tecnológico de Sonora, Ciudad Obregón 85000, Mexico
| | - Javier R. Reyna-Granados
- Departamento de Ciencias Agronómicas y Veterinarias, Instituto Tecnológico de Sonora, Ciudad Obregón 85000, Mexico
| | - Pablo Luna-Nevárez
- Departamento de Ciencias Agronómicas y Veterinarias, Instituto Tecnológico de Sonora, Ciudad Obregón 85000, Mexico
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Ricci CG, Philpott JM, Torgrimson MR, Freeberg AM, Narasimamurthy R, de Barros EP, Amaro R, Virshup DM, McCammon JA, Partch CL. Markovian State Models uncover Casein Kinase 1 dynamics that govern circadian period. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.17.633651. [PMID: 39896482 PMCID: PMC11785140 DOI: 10.1101/2025.01.17.633651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
Circadian rhythms in mammals are tightly regulated through phosphorylation of Period (PER) proteins by Casein Kinase 1 (CK1, subtypes δ and ε). CK1 acts on at least two different regions of PER with opposing effects: phosphorylation of phosphodegron (pD) regions leads to PER degradation, while phosphorylation of the Familial Advanced Sleep Phase (FASP) region leads to PER stabilization. To investigate how substrate selectivity is encoded by the conformational dynamics of CK1, we performed a large set of independent molecular dynamics (MD) simulations of wildtype CK1 and the tau mutant (R178C) that biases kinase activity toward a pD. We used Markovian State Models (MSMs) to integrate the simulations into a single model of the conformational landscape of CK1 and used Gaussian accelerated molecular dynamics (GaMD) to build the first molecular model of CK1 and the unphosphorylated FASP motif. Together, these findings provide a mechanistic view of CK1, establishing how the activation loop acts as a key molecular switch to control substrate selectivity. We show that the tau mutant favors an alternative conformation of the activation loop and significantly accelerates the dynamics of CK1. This reshapes the binding cleft in a way that impairs FASP binding and would ultimately lead to PER destabilization and shorter circadian periods. Finally, we identified an allosteric pocket that could be targeted to bias this molecular switch. Our integrated approach offers a detailed model of CK1's conformational landscape and its relevance to normal, mutant, and druggable circadian timekeeping.
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Affiliation(s)
- Clarisse Gravina Ricci
- Department of Chemistry and Biochemistry, University of California San Diego, San Diego, California, United States
- Current address: D.E. Shaw Research, New York, New York, United States
| | - Jonathan M. Philpott
- Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California, United States
| | - Megan R. Torgrimson
- Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California, United States
| | - Alfred M. Freeberg
- Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California, United States
| | - Rajesh Narasimamurthy
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore
| | - Emilia Pécora de Barros
- Department of Chemistry and Biochemistry, University of California San Diego, San Diego, California, United States
| | - Rommie Amaro
- Department of Chemistry and Biochemistry, University of California San Diego, San Diego, California, United States
| | - David M. Virshup
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore
- Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, United States
| | - J. Andrew McCammon
- Department of Chemistry and Biochemistry, University of California San Diego, San Diego, California, United States
| | - Carrie L. Partch
- Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California, United States
- Center for Circadian Biology, University of California San Diego, San Diego, California, United States
- Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, California, United States
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Zhao B, Nepovimova E, Wu Q. The role of circadian rhythm regulator PERs in oxidative stress, immunity, and cancer development. Cell Commun Signal 2025; 23:30. [PMID: 39825442 PMCID: PMC11740368 DOI: 10.1186/s12964-025-02040-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 01/11/2025] [Indexed: 01/20/2025] Open
Abstract
The complex interaction between circadian rhythms and physiological functions is essential for maintaining human health. At the heart of this interaction lies the PERIOD proteins (PERs), pivotal to the circadian clock, influencing the timing of physiological and behavioral processes and impacting oxidative stress, immune functionality, and tumorigenesis. PER1 orchestrates the cooperation of the enzyme GPX1, modulating mitochondrial dynamics in sync with daily rhythms and oxidative stress, thus regulating the mechanisms managing energy substrates. PERs in innate immune cells modulate the temporal patterns of NF-κB and TNF-α activities, as well as the response to LPS-induced toxic shock, initiating inflammatory responses that escalate into chronic inflammatory conditions. Crucially, PERs modulate cancer cell behaviors including proliferation, apoptosis, and migration by influencing the levels of cell cycle proteins and stimulating the expression of oncogenes c-Myc and MDM2. PER2/3, as antagonists in cancer stem cell biology, play important roles in differentiating cancer stem cells and in maintaining their stemness. Importantly, the expression of Pers serve as a significant factor for early cancer diagnosis and prognosis. This review delves into the link between circadian rhythm regulator PERs, disruptions in circadian rhythm, and oncogenesis. We examine the evidence that highlights how dysfunctions in PERs activities initiate cancer development, aid tumor growth, and modify cancer cell metabolism through pathways involved in oxidative stress and immune system. Comprehending these connections opens new pathways for the development of circadian rhythm-based therapeutic strategies, with the aims of boosting immune responses and enhancing cancer treatments.
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Affiliation(s)
- Baimei Zhao
- College of Life Science, Yangtze University, Jingzhou, 434025, China
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Science, University of Hradec Králové, Hradec Králové , 500 03, Czech Republic
| | - Qinghua Wu
- College of Life Science, Yangtze University, Jingzhou, 434025, China.
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Maghbooli M, Karami M, Mohammadi V. Association of chronotype and timing of interferon injection with severity of IFNβ-induced flu-like syndrome in Multiple sclerosis (MS) patients. J Clin Neurosci 2024; 128:110811. [PMID: 39197331 DOI: 10.1016/j.jocn.2024.110811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 08/21/2024] [Accepted: 08/23/2024] [Indexed: 09/01/2024]
Abstract
BACKGROUND Although Interferon-beta (IFNβ) has long been approved as a disease-modifying therapy (DMT) for Multiple sclerosis (MS), flu-like syndrome (FLS) persists as a common adverse effect of interferon therapy. Given the importance of circadian rhythm in regulating physiological processes, we aimed to assess the relationship between patient's chronotype and time of interferon injection with FLS score in MS patients receiving IFNβ. METHODS A cross-sectional study was conducted on 118 MS patients who were referred to the clinic of neurology of Zanjan Vali-e-Asr Hospital for interferon injection. The included were invited to complete a morningness-eveningness questionnaire (MEQ) assessing patients' chronotype. The following data were extracted from patients' record: age, gender, duration of interferon treatment, type of interferon taken, time of interferon injection (morning/evening), FLS score, MS subtype, and usage of pain killers. All data found were imported and statistically analyzed in SPSS ver.26. RESULTS According to the patients' record, 114 (96.6%) patients had experienced post-interferon injection FLS with different severities. Statistical analysis revealed no significant relationship between the patient's chronotype and FLS score. Nevertheless, the FLS score was significantly higher in those who had evening injections. CONCLUSIONS Time of interferon injection was significantly associated with FLS score, with higher FLS score following evening injection. However, no significant relationship was found between the FLS score and the patient's chronotype. It is recommended that further studies assessing circadian rhythm using laboratory tests such as melatonin measurement need to be undertaken to investigate the association of circadian rhythm with post-interferon injection FLS.
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Affiliation(s)
- Mehdi Maghbooli
- Department of Neurology, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mobin Karami
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Vahid Mohammadi
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
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Lin CP, Lin CL, Wu HC, Chung CH, Chien WC. Risk of Herpes Simplex virus type 1 (HSV-1) among patients with insomnia: A retrospective cohort study. Medicine (Baltimore) 2024; 103:e39112. [PMID: 39093735 PMCID: PMC11296460 DOI: 10.1097/md.0000000000039112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 07/08/2024] [Indexed: 08/04/2024] Open
Abstract
The aim of this study was to explore the risk of Simplex virus type 1 (HSV-1) in patients with insomnia. This study applied a population-based retrospective cohort design. A total of 50,210 patients aged ≥ 20 years who had received a diagnosis of insomnia between 2000 and 2015. They were identified according to the corresponding International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. The control cohort comprised 100,420 age-matched and sex-matched patients. Data from the Taiwan National Health Insurance Research Database were employed from 2000 to 2015. The overall incidence of HSV-1 in the insomnia cohort was significantly higher than that in the comparison cohort (3.10 vs 0.33 per 1000 person-years). Patients with insomnia had a higher risk of HSV-1 infection, compared with the comparisons (hazard ratio (HR) = 4.33, 95% confidence interval (CI) 2.18-5.58). For individuals divided into 3 age groups (≤40, 41-65, and >65 years old), the HSV-1 infection risk of the insomnia cohort was significantly greater than that of the comparisons. As the duration of insomnia increases, the risk of HSV-1 occurrence decreases.
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Affiliation(s)
- Chun-Ping Lin
- Department of Nursing, Shu-Zen Junior College of Medicine, and Management, Kaohsiung, Taiwan
| | - Chia-Ling Lin
- Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Hsueh-Ching Wu
- Department of Nursing, Hsin Sheng Junior College of Medical Care and Management, Taoyuan, Taiwan
| | - Chi-Hsiang Chung
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Taiwanese Injury Prevention and Safety Promotion Association (TIPSPA), Taipei, Taiwan
| | - Wu-Chien Chien
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Department of Medical Research, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan
- Graduate Institute of Science, National Defense Medical Center, Taipei, Taiwan
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Lin Y, He L, Cai Y, Wang X, Wang S, Li F. The role of circadian clock in regulating cell functions: implications for diseases. MedComm (Beijing) 2024; 5:e504. [PMID: 38469551 PMCID: PMC10925886 DOI: 10.1002/mco2.504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 01/28/2024] [Accepted: 01/30/2024] [Indexed: 03/13/2024] Open
Abstract
The circadian clock system orchestrates daily behavioral and physiological rhythms, facilitating adaptation to environmental and internal oscillations. Disruptions in circadian rhythms have been linked to increased susceptibility to various diseases and can exacerbate existing conditions. This review delves into the intricate regulation of diurnal gene expression and cell function by circadian clocks across diverse tissues. . Specifically, we explore the rhythmicity of gene expressions, behaviors, and functions in both immune and non-immune cells, elucidating the regulatory effects and mechanisms imposed by circadian clocks. A detailed discussion is centered on elucidating the complex functions of circadian clocks in regulating key cellular signaling pathways. We further review the circadian regulation in diverse diseases, with a focus on inflammatory diseases, cancers, and systemic diseases. By highlighting the intimate interplay between circadian clocks and diseases, especially through clock-controlled cell function, this review contributes to the development of novel disease intervention strategies. This enhanced understanding holds significant promise for the design of targeted therapies that can exploit the circadian regulation mechanisms for improved treatment efficacy.
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Affiliation(s)
- Yanke Lin
- Infectious Diseases InstituteGuangzhou Eighth People's HospitalGuangzhou Medical UniversityGuangzhouChina
- Guangdong TCRCure Biopharma Technology Co., Ltd.GuangzhouChina
| | | | - Yuting Cai
- School of Pharmaceutical SciencesGuangzhou University of Chinese MedicineGuangzhouChina
| | - Xiaokang Wang
- Department of PharmacyShenzhen Longhua District Central HospitalShenzhenChina
| | - Shuai Wang
- School of Pharmaceutical SciencesGuangzhou University of Chinese MedicineGuangzhouChina
| | - Feng Li
- Infectious Diseases InstituteGuangzhou Eighth People's HospitalGuangzhou Medical UniversityGuangzhouChina
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Joseph TT, Schuch V, Hossack DJ, Chakraborty R, Johnson EL. Melatonin: the placental antioxidant and anti-inflammatory. Front Immunol 2024; 15:1339304. [PMID: 38361952 PMCID: PMC10867115 DOI: 10.3389/fimmu.2024.1339304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 01/15/2024] [Indexed: 02/17/2024] Open
Abstract
Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone with many physiological and biological roles. Melatonin is an antioxidant, anti-inflammatory, free radical scavenger, circadian rhythm regulator, and sleep hormone. However, its most popular role is the ability to regulate sleep through the circadian rhythm. Interestingly, recent studies have shown that melatonin is an important and essential hormone during pregnancy, specifically in the placenta. This is primarily due to the placenta's ability to synthesize its own melatonin rather than depending on the pineal gland. During pregnancy, melatonin acts as an antioxidant and anti-inflammatory, which is necessary to ensure a stable environment for both the mother and the fetus. It is an essential antioxidant in the placenta because it reduces oxidative stress by constantly scavenging for free radicals, i.e., maintain the placenta's integrity. In a healthy pregnancy, the maternal immune system is constantly altered to accommodate the needs of the growing fetus, and melatonin acts as a key anti-inflammatory by regulating immune homeostasis during early and late gestation. This literature review aims to identify and summarize melatonin's role as a powerful antioxidant and anti-inflammatory that reduces oxidative stress and inflammation to maintain a favorable homeostatic environment in the placenta throughout gestation.
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Affiliation(s)
- Tyana T. Joseph
- Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States
| | - Viviane Schuch
- Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States
| | - Daniel J. Hossack
- Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States
| | - Rana Chakraborty
- Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Erica L. Johnson
- Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States
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Zhang K, Mi F, Li X, Wang Z, Jiang F, Song E, Guo P, Lan X. Detection of genetic variation in bovine CRY1 gene and its associations with carcass traits. Anim Biotechnol 2023; 34:3387-3394. [PMID: 36448652 DOI: 10.1080/10495398.2022.2149547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
The biological clock (also known as circadian clock) is closely related to growth and development, metabolism, and diseases in animals. As a part of the circadian clock, the cryptochrome circadian regulator 1 (CRY1) gene is involved in the regulation of biological processes such as osteogenesis, energy metabolism and cell proliferation, however, few studies have been reported on the relationship between this gene and animal carcass traits. Herein, a total of four insertion/deletion (InDel) loci within the CRY1 gene were detected in Shandong Black Cattle Genetic Resource (SDBCGR) population (n = 433). Among them, the P1-6-bp-del locus was polymorphic in population of interest. Moreover, the P1-6-bp-del locus showed two genotypes, with a higher insertion/insertion (II) genotype frequency (0.751) than insertion/deletion (ID) genotype frequency (0.249). Correlation analysis showed that the P1-6-bp-del locus polymorphisms were significantly associated with twenty carcass traits (e.g., slaughter weight, limb weight, and belly meat weight). Individuals with II genotype were significantly better than those with ID genotype for eighteen carcass traits. Therefore, the P1-6-bp-del locus of the CRY1 gene can be used as a molecular marker for beef cattle breeding.
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Affiliation(s)
- Kejing Zhang
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Fang Mi
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xuelan Li
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Zhiying Wang
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Fugui Jiang
- Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, China
| | - Enliang Song
- Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, China
| | - Peng Guo
- College of Computer and Information Engineering, Tianjin Agricultural University, Tianjin, China
| | - Xianyong Lan
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
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11
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Castillejos-López M, Romero Y, Varela-Ordoñez A, Flores-Soto E, Romero-Martinez BS, Velázquez-Cruz R, Vázquez-Pérez JA, Ruiz V, Gomez-Verjan JC, Rivero-Segura NA, Camarena Á, Torres-Soria AK, Gonzalez-Avila G, Sommer B, Solís-Chagoyán H, Jaimez R, Torres-Espíndola LM, Aquino-Gálvez A. Hypoxia Induces Alterations in the Circadian Rhythm in Patients with Chronic Respiratory Diseases. Cells 2023; 12:2724. [PMID: 38067152 PMCID: PMC10706372 DOI: 10.3390/cells12232724] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Revised: 11/08/2023] [Accepted: 11/23/2023] [Indexed: 12/18/2023] Open
Abstract
The function of the circadian cycle is to determine the natural 24 h biological rhythm, which includes physiological, metabolic, and hormonal changes that occur daily in the body. This cycle is controlled by an internal biological clock that is present in the body's tissues and helps regulate various processes such as sleeping, eating, and others. Interestingly, animal models have provided enough evidence to assume that the alteration in the circadian system leads to the appearance of numerous diseases. Alterations in breathing patterns in lung diseases can modify oxygenation and the circadian cycles; however, the response mechanisms to hypoxia and their relationship with the clock genes are not fully understood. Hypoxia is a condition in which the lack of adequate oxygenation promotes adaptation mechanisms and is related to several genes that regulate the circadian cycles, the latter because hypoxia alters the production of melatonin and brain physiology. Additionally, the lack of oxygen alters the expression of clock genes, leading to an alteration in the regularity and precision of the circadian cycle. In this sense, hypoxia is a hallmark of a wide variety of lung diseases. In the present work, we intended to review the functional repercussions of hypoxia in the presence of asthma, chronic obstructive sleep apnea, lung cancer, idiopathic pulmonary fibrosis, obstructive sleep apnea, influenza, and COVID-19 and its repercussions on the circadian cycles.
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Affiliation(s)
- Manuel Castillejos-López
- Departamento de Epidemiología e Infectología Hospitalaria, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico;
| | - Yair Romero
- Facultad de Ciencias, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico;
| | - Angelica Varela-Ordoñez
- Red MEDICI, Carrera de Médico Cirujano, Facultad de Estudios Superiores de Iztacala Universidad Nacional Autónoma de México, Mexico City 54090, Mexico; (A.V.-O.); (A.K.T.-S.)
| | - Edgar Flores-Soto
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico; (E.F.-S.); (B.S.R.-M.); (R.J.)
| | - Bianca S. Romero-Martinez
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico; (E.F.-S.); (B.S.R.-M.); (R.J.)
| | - Rafael Velázquez-Cruz
- Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico;
| | - Joel Armando Vázquez-Pérez
- Laboratorio de Biología Molecular de Enfermedades Emergentes y EPOC, Instituto Nacional de Enferdades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico;
| | - Víctor Ruiz
- Laboratorio de Biología Molecular, Departamento de Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico;
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional (INP), Mexico City 11340, Mexico
| | - Juan C. Gomez-Verjan
- Dirección de Investigación, Instituto Nacional de Geriatría (INGER), Mexico City 10200, Mexico; (J.C.G.-V.); (N.A.R.-S.)
| | - Nadia A. Rivero-Segura
- Dirección de Investigación, Instituto Nacional de Geriatría (INGER), Mexico City 10200, Mexico; (J.C.G.-V.); (N.A.R.-S.)
| | - Ángel Camarena
- Laboratorio de Inmunobiología y Genética, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico;
| | - Ana Karen Torres-Soria
- Red MEDICI, Carrera de Médico Cirujano, Facultad de Estudios Superiores de Iztacala Universidad Nacional Autónoma de México, Mexico City 54090, Mexico; (A.V.-O.); (A.K.T.-S.)
| | - Georgina Gonzalez-Avila
- Laboratorio de Oncología Biomédica, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico;
| | - Bettina Sommer
- Departamento de Investigación en Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico;
| | - Héctor Solís-Chagoyán
- Laboratorio de Neurobiología Cognitiva, Centro de Investigación en Ciencias Cognitivas, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico;
| | - Ruth Jaimez
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico; (E.F.-S.); (B.S.R.-M.); (R.J.)
| | | | - Arnoldo Aquino-Gálvez
- Laboratorio de Biología Molecular, Departamento de Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico;
- Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico
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Alvarez-García L, Sánchez-García FJ, Vázquez-Pichardo M, Moreno-Altamirano MM. Chikungunya Virus, Metabolism, and Circadian Rhythmicity Interplay in Phagocytic Cells. Metabolites 2023; 13:1143. [PMID: 37999239 PMCID: PMC10672914 DOI: 10.3390/metabo13111143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 10/28/2023] [Accepted: 10/31/2023] [Indexed: 11/25/2023] Open
Abstract
Chikungunya virus (CHIKV) is transmitted to humans by mosquitoes of the genus Aedes, causing the chikungunya fever disease, associated with inflammation and severe articular incapacitating pain. There has been a worldwide reemergence of chikungunya and the number of cases increased to 271,006 in 2022 in the Americas alone. The replication of CHIKV takes place in several cell types, including phagocytic cells. Monocytes and macrophages are susceptible to infection by CHIKV; at the same time, they provide protection as components of the innate immune system. However, in host-pathogen interactions, CHIKV might have the ability to alter the function of immune cells, partly by rewiring the tricarboxylic acid cycle. Some viral evasion mechanisms depend on the metabolic reprogramming of immune cells, and the cell metabolism is intertwined with circadian rhythmicity; thus, a circadian immunovirometabolism axis may influence viral pathogenicity. Therefore, analyzing the interplay between viral infection, circadian rhythmicity, and cellular metabolic reprogramming in human macrophages could shed some light on the new field of immunovirometabolism and eventually contribute to the development of novel drugs and therapeutic approaches based on circadian rhythmicity and metabolic reprogramming.
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Affiliation(s)
- Linamary Alvarez-García
- Laboratorio de Inmunorregulación, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas del IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Casco de Santo Tomás, Mexico City 11340, Mexico; (L.A.-G.); (F.J.S.-G.); (M.V.-P.)
| | - F. Javier Sánchez-García
- Laboratorio de Inmunorregulación, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas del IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Casco de Santo Tomás, Mexico City 11340, Mexico; (L.A.-G.); (F.J.S.-G.); (M.V.-P.)
| | - Mauricio Vázquez-Pichardo
- Laboratorio de Inmunorregulación, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas del IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Casco de Santo Tomás, Mexico City 11340, Mexico; (L.A.-G.); (F.J.S.-G.); (M.V.-P.)
- Laboratorio de Arbovirus, Departamento de Virología, Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE), Secretaría de Salud, Francisco de P. Miranda 177, Col. Lomas de Plateros, Mexico City 01480, Mexico
| | - M. Maximina Moreno-Altamirano
- Laboratorio de Inmunorregulación, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas del IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Casco de Santo Tomás, Mexico City 11340, Mexico; (L.A.-G.); (F.J.S.-G.); (M.V.-P.)
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13
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Mazur M, Rakus K, Adamek M, Surachetpong W, Chadzinska M, Pijanowski L. Effects of light and circadian clock on the antiviral immune response in zebrafish. FISH & SHELLFISH IMMUNOLOGY 2023; 140:108979. [PMID: 37532067 DOI: 10.1016/j.fsi.2023.108979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Revised: 07/28/2023] [Accepted: 07/30/2023] [Indexed: 08/04/2023]
Abstract
The circadian clock mechanism, which is evolutionarily conserved across various organisms, plays a crucial role in synchronizing physiological responses to external conditions, primarily in response to light availability. By maintaining homeostasis of biological processes and behavior, the circadian clock serves as a key regulator. This biological mechanism also coordinates diurnal oscillations of the immune response during infections. However there is limited information available regarding the influence of circadian oscillation on immune regulation, especially in lower vertebrates like teleost fish. Therefore, the present study aimed to investigate the effects of light and the timing of infection induction on the antiviral immune response in zebrafish. To explore the relationship between the timing of infection and the response activated by viral pathogens, we used a zebrafish model infected with tilapia lake virus (TiLV). Our findings demonstrated that light availability significantly affects the antiviral immune response and the functioning of the molecular clock mechanism during TiLV infection. This is evident through alterations in the expression of major core clock genes and the regulation of TiLV replication and type I IFN pathway genes in the kidney of fish maintained under LD (light-dark) conditions compared to constant darkness (DD) conditions. Moreover, infection induced during the light phase of the LD cycle, in contrast to nocturnal infection, also exhibited similar effects on the expression of genes associated with the antiviral response. This study indicates a more effective mechanism of the zebrafish antiviral response during light exposure, which inherently involves modification of the expression of key components of the molecular circadian clock. It suggests that the zebrafish antiviral response to infection is regulated by both light and the circadian clock.
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Affiliation(s)
- Mikolaj Mazur
- Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, PL30-387, Krakow, Poland; Doctoral School of Exact and Natural Sciences, Jagiellonian University, Łojasiewicza 11, PL30-348, Krakow, Poland
| | - Krzysztof Rakus
- Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, PL30-387, Krakow, Poland
| | - Mikolaj Adamek
- Fish Disease Research Unit, University of Veterinary Medicine Hannover, Buenteweg 17, 30559, Hannover, Germany
| | - Win Surachetpong
- Department of Veterinary Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, 50 Ngam Wong Wan Road, Ladyao, Chatuchak, 10900, Bangkok, Thailand
| | - Magdalena Chadzinska
- Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, PL30-387, Krakow, Poland
| | - Lukasz Pijanowski
- Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, PL30-387, Krakow, Poland.
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14
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Shafaati M, Sadeghniiat K, Priyanka, Najafia A, Zandi M, Akbarpour S, Choudhary OP. The relevance of the circadian timing system role in patients with HIV/AIDS: a quick glance. Int J Surg 2023; 109:2831-2834. [PMID: 36928027 PMCID: PMC10498842 DOI: 10.1097/js9.0000000000000103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 11/16/2022] [Indexed: 03/18/2023]
Affiliation(s)
- Maryam Shafaati
- Occupational Sleep Research Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Department of Microbiology, Faculty Science, Jahrom Branch, Islamic Azad University, Jahrom, Iran
| | - Khosro Sadeghniiat
- Occupational Sleep Research Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Priyanka
- Department of Veterinary Microbiology, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University (GADVASU), Rampura Phul, Bathinda, Punjab, India
| | - Arezu Najafia
- Occupational Sleep Research Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Milad Zandi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Samaneh Akbarpour
- Occupational Sleep Research Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Sleep Breathing Disorders Research Center (SBDRC), Tehran University of Medical Sciences, Tehran, Iran
| | - Om Prakash Choudhary
- Department of Veterinary Anatomy and Histology, College of Veterinary Sciences and Animal Husbandry, Central Agricultural University (I), Selesih, Aizawl, Mizoram, India
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França DCH, Fujimori M, de Queiroz AA, Borges MD, Magalhães Neto AM, de Camargos PJV, Ribeiro EB, França EL, Honorio-França AC, Fagundes-Triches DLG. Melatonin and Cytokines Modulate Daily Instrumental Activities of Elderly People with SARS-CoV-2 Infection. Int J Mol Sci 2023; 24:ijms24108647. [PMID: 37239991 DOI: 10.3390/ijms24108647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 05/03/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
The Comprehensive Geriatric Assessment analyzes the health and quality of life of the elderly. Basic and instrumental daily activities may be compromised due to neuroimmunoendocrine changes, and studies suggest that possible immunological changes occur during infections in the elderly. Thus, this study aimed to analyze cytokine and melatonin levels in serum and correlate the Comprehensive Geriatric Assessment in elderly patients with SARS-CoV-2 infection. The sample consisted of 73 elderly individuals, 43 of whom were without infection and 30 of whom had positive diagnoses of COVID-19. Blood samples were collected to quantify cytokines by flow cytometry and melatonin by ELISA. In addition, structured and validated questionnaires were applied to assess basic (Katz) and instrumental (Lawton and Brody) activities. There was an increase in IL-6, IL-17, and melatonin in the group of elderly individuals with infection. In addition, a positive correlation was observed between melatonin and IL-6 and IL-17 in elderly patients with SARS-CoV-2 infection. Furthermore, there was a reduction in the score of the Lawton and Brody Scale in the infected elderly. These data suggest that the melatonin hormone and inflammatory cytokines are altered in the serum of the elderly with SARS-CoV-2 infection. In addition, there is a degree of dependence, mainly regarding the performance of daily instrumental activities, in the elderly. The considerable impact on the elderly person's ability to perform everyday tasks necessary for independent living is an extremely important result, and changes in cytokines and melatonin probably are associated with alterations in these daily activities of the elderly.
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Affiliation(s)
| | - Mahmi Fujimori
- Biological and Health Sciences Institute, Federal University of Mato Grosso, Barra do Garças 78605-091, Mato Grosso, Brazil
| | - Adriele Ataídes de Queiroz
- Biological and Health Sciences Institute, Federal University of Mato Grosso, Barra do Garças 78605-091, Mato Grosso, Brazil
| | - Maraísa Delmut Borges
- Biological and Health Sciences Institute, Federal University of Mato Grosso, Barra do Garças 78605-091, Mato Grosso, Brazil
| | - Aníbal Monteiro Magalhães Neto
- Biological and Health Sciences Institute, Federal University of Mato Grosso, Barra do Garças 78605-091, Mato Grosso, Brazil
| | | | - Elton Brito Ribeiro
- Health Sciences Institute, Federal University of Mato Grosso, Sinop 78557-287, Mato Grosso, Brazil
| | - Eduardo Luzía França
- Biological and Health Sciences Institute, Federal University of Mato Grosso, Barra do Garças 78605-091, Mato Grosso, Brazil
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16
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Amidfar M, Garcez ML, Kim YK. The shared molecular mechanisms underlying aging of the brain, major depressive disorder, and Alzheimer's disease: The role of circadian rhythm disturbances. Prog Neuropsychopharmacol Biol Psychiatry 2023; 123:110721. [PMID: 36702452 DOI: 10.1016/j.pnpbp.2023.110721] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 01/07/2023] [Accepted: 01/19/2023] [Indexed: 01/24/2023]
Abstract
An association with circadian clock function and pathophysiology of aging, major depressive disorder (MDD), and Alzheimer's disease (AD) is well established and has been proposed as a factor in the development of these diseases. Depression and changes in circadian rhythm have been increasingly suggested as the two primary overlapping and interpenetrating changes that occur with aging. The relationship between AD and depression in late life is not completely understood and probably is complex. Patients with major depression or AD suffer from disturbed sleep/wake cycles and altered rhythms in daily activities. Although classical monoaminergic hypotheses are traditionally proposed to explain the pathophysiology of MDD, several clinical and preclinical studies have reported a strong association between circadian rhythm and mood regulation. In addition, a large body of evidence supports an association between disruption of circadian rhythm and AD. Some clock genes are dysregulated in rodent models of depression. If aging, AD, and MDD share a common biological basis in pathophysiology, common therapeutic tools could be investigated for their prevention and treatment. Nitro-oxidative stress (NOS), for example, plays a fundamental role in aging, as well as in the pathogenesis of AD and MDD and is associated with circadian clock disturbances. Thus, development of therapeutic possibilities with these NOS-related conditions is advisable. This review describes recent findings that link disrupted circadian clocks to aging, MDD, and AD and summarizes the experimental evidence that supports connections between the circadian clock and molecular pathologic factors as shared common pathophysiological mechanisms underlying aging, AD, and MDD.
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Affiliation(s)
- Meysam Amidfar
- Department of Neuroscience, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Michelle Lima Garcez
- Laboratory of Translational Neuroscience, Department of Biochemistry, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina, Brazil
| | - Yong-Ku Kim
- Department of Psychiatry, College of Medicine, Korea University, Seoul, South Korea.
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Zandi M, Shafaati M, Shapshak P, Hashemnia SMR. Monkeypox virus replication underlying circadian rhythm networks. J Neurovirol 2023; 29:1-7. [PMID: 36719593 PMCID: PMC9888333 DOI: 10.1007/s13365-023-01118-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 01/11/2023] [Accepted: 01/21/2023] [Indexed: 02/01/2023]
Abstract
The mammalian brain has an endogenous central circadian clock that regulates central and peripheral cellular activities. At the molecular level, this day-night cycle induces the expression of upstream and downstream transcription factors that influence the immune system and the severity of viral infections over time. In addition, there are also circadian effects on host tolerance pathways. This stimulates adaptation to normal changes in environmental conditions and requirements (including light and food). These rhythms influence the pharmacokinetics and efficacy of therapeutic drugs and vaccines. The importance of circadian systems in regulating viral infections and the host response to viruses is currently of great importance for clinical management. With the knowledge gained from the COVID-19 pandemic, it is important to address any outbreak of viral infection that could become endemic and to quickly focus research on any knowledge gaps. For example, responses to booster vaccination COVID-19 may have different time-dependent patterns during circadian cycles. There may be a link between reactivation of latently infected viruses and regulation of circadian rhythms. In addition, mammals may show different seasonal antiviral responses in winter and summer. This article discusses the importance of the host circadian clock during monkeypox infection and immune system interactions.
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Affiliation(s)
- Milad Zandi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
| | - Maryam Shafaati
- Department of Microbiology, Faculty Science, Jahrom Branch, Islamic Azad University, Jahrom, Iran
| | - Paul Shapshak
- Global Disease Institute, Tampa General Hospital, Division of Infectious Diseases and International Health, Department of Internal Medicine, Morsani College of Medicine, Tampa, FL, USA
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Viloria Winnett A, Porter MK, Romano AE, Savela ES, Akana R, Shelby N, Reyes JA, Schlenker NW, Cooper MM, Carter AM, Ji J, Barlow JT, Tognazzini C, Feaster M, Goh YY, Ismagilov RF. Morning SARS-CoV-2 Testing Yields Better Detection of Infection Due to Higher Viral Loads in Saliva and Nasal Swabs upon Waking. Microbiol Spectr 2022; 10:e0387322. [PMID: 36287073 PMCID: PMC9769854 DOI: 10.1128/spectrum.03873-22] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 10/03/2022] [Indexed: 01/10/2023] Open
Abstract
Optimizing specimen collection methods to achieve the most reliable SARS-CoV-2 detection for a given diagnostic sensitivity would improve testing and minimize COVID-19 outbreaks. From September 2020 to April 2021, we performed a household-transmission study in which participants self-collected specimens every morning and evening throughout acute SARS-CoV-2 infection. Seventy mildly symptomatic participants collected saliva, and of those, 29 also collected nasal swab specimens. Viral load was quantified in 1,194 saliva and 661 nasal swab specimens using a high-analytical-sensitivity reverse transcription-quantitative PCR (RT-qPCR) assay. Viral loads in both saliva and nasal swab specimens were significantly higher in morning-collected specimens than in evening-collected specimens after symptom onset. This aspect of the biology of SARS-CoV-2 infection has implications for diagnostic testing. We infer that morning collection would have resulted in significantly improved detection and that this advantage would be most pronounced for tests with low to moderate analytical sensitivity. Collecting specimens for COVID-19 testing in the morning offers a simple and low-cost improvement to clinical diagnostic sensitivity of low- to moderate-analytical-sensitivity tests. IMPORTANCE Our findings suggest that collecting saliva and nasal swab specimens in the morning immediately after waking yields higher SARS-CoV-2 viral loads than collection later in the day. The higher viral loads from morning specimen collection are predicted to significantly improve detection of SARS-CoV-2 in symptomatic individuals, particularly when using moderate- to low-analytical-sensitivity COVID-19 diagnostic tests, such as rapid antigen tests.
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Affiliation(s)
| | | | - Anna E. Romano
- California Institute of Technology, Pasadena, California, USA
| | - Emily S. Savela
- California Institute of Technology, Pasadena, California, USA
| | - Reid Akana
- California Institute of Technology, Pasadena, California, USA
| | - Natasha Shelby
- California Institute of Technology, Pasadena, California, USA
| | | | | | | | | | - Jenny Ji
- California Institute of Technology, Pasadena, California, USA
| | - Jacob T. Barlow
- California Institute of Technology, Pasadena, California, USA
| | - Colten Tognazzini
- City of Pasadena Public Health Department, Pasadena, California, USA
| | - Matthew Feaster
- City of Pasadena Public Health Department, Pasadena, California, USA
| | - Ying-Ying Goh
- City of Pasadena Public Health Department, Pasadena, California, USA
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Romdhani M, Vedasalam S, Souissi A, Fessi MS, Varma A, Taheri M, Ghram A, Al Naama A, Mkaouer B, Ben Saad H, Dergaa I. Is there a diurnal variation of COVID-19 patients warranting presentation to the health centre? A chronobiological observational cross-sectional study. Ann Med 2022; 54:3060-3068. [PMID: 36308396 PMCID: PMC9635474 DOI: 10.1080/07853890.2022.2136399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 10/07/2022] [Accepted: 10/10/2022] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND The circadian clock regulates the function of the immune system, the replication of viruses, and the magnitude of infections. The aim of this study was to analyse whether hospital attendance in Coronavirus disease 2019 (COVID-19) patients presents a diurnal variation. METHODS Data from the electronic medical records of 1094 COVID-19 patients who presented to a Health Centre in Qatar during the month of July 2020 was retrospectively analysed. The following demographic (i.e. time of day (TOD), sex, age), clinical (i.e. cycle threshold (CT), temperature, oxy-haemoglobin saturation and resting heart-rate), biochemical (i.e. uraemia, glycaemia and albuminia) and haematological (i.e. leukocytes, erythrocytes ad platelets) parameters were collected. RESULTS Univariate analysis showed a significant effect of TOD on hospital admission (p < 0.001), with patients attending the health care centre more during the active behavioural phase (08h00-00h00) compared to the resting phase (00h00-08h00). COVID-19 infection blunted the circadian rhythms of core body temperature, neutrophils and leukocytes family and shifted the circadian rhythms of resting heart-rate and uraemia. Correlation analysis showed a near perfect negative correlation between the age of patients and the TOD (r=-0.97), with older patients attending the care centre earlier during the day. CONCLUSION COVID-19 infection affected the circadian rhythms of the host through disrupting the circadian rhythms of core temperature and innate immunity mediators. Old patients attend the health care centre earlier compared to younger ones. However, CT during polymerase chain reaction-test was unaffected by the TOD, which limits the conclusion that COVID-19 viral infection exhibits diurnal variation.
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Affiliation(s)
- Mohamed Romdhani
- Research Unit: Physical Activity, Sport, and Health, UR18JS01, National Observatory of Sport, Tunis, Tunisia
- Motricité-Interactions-Performance, MIP, UR4334, Le Mans Université, Le Mans, France
| | | | - Amine Souissi
- Sports Medicine, Universite de Sousse, Faculte de Medecine de Sousse, Sousse, Tunisia
| | - Mohamed Saifeddin Fessi
- Research Unit: Physical Activity, Sport, and Health, UR18JS01, National Observatory of Sport, Tunis, Tunisia
| | - Amit Varma
- Primary Health Care Corporation, Doha, Qatar
| | - Morteza Taheri
- Department of Sport Sciences, Imam Khomeini International University, Qazvi, Iran
| | - Amine Ghram
- Healthy Living for Pandemic Event Protection (HL – PIVOT) Network, Chicago, IL, US
| | | | | | - Helmi Ben Saad
- Laboratoire de Recherche (LR12SP09) “Insuffisance cardiaque” Sousse, Faculté de Médecine de Sousse, Hôpital Farhat HACHED, Université de Sousse, Sousse, Tunisie
| | - Ismail Dergaa
- Research Unit: Physical Activity, Sport, and Health, UR18JS01, National Observatory of Sport, Tunis, Tunisia
- Primary Health Care Corporation, Doha, Qatar
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Papagerakis S, Said R, Ketabat F, Mahmood R, Pundir M, Lobanova L, Guenther G, Pannone G, Lavender K, McAlpin BR, Moreau A, Chen X, Papagerakis P. When the clock ticks wrong with COVID-19. Clin Transl Med 2022; 12:e949. [PMID: 36394205 PMCID: PMC9670202 DOI: 10.1002/ctm2.949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 06/06/2022] [Accepted: 06/11/2022] [Indexed: 11/18/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronavirus family that causes the novel coronavirus disease first diagnosed in 2019 (COVID-19). Although many studies have been carried out in recent months to determine why the disease clinical presentations and outcomes can vary significantly from asymptomatic to severe or lethal, the underlying mechanisms are not fully understood. It is likely that unique individual characteristics can strongly influence the broad disease variability; thus, tailored diagnostic and therapeutic approaches are needed to improve clinical outcomes. The circadian clock is a critical regulatory mechanism orchestrating major physiological and pathological processes. It is generally accepted that more than half of the cell-specific genes in any given organ are under circadian control. Although it is known that a specific role of the circadian clock is to coordinate the immune system's steady-state function and response to infectious threats, the links between the circadian clock and SARS-CoV-2 infection are only now emerging. How inter-individual variability of the circadian profile and its dysregulation may play a role in the differences noted in the COVID-19-related disease presentations, and outcome remains largely underinvestigated. This review summarizes the current evidence on the potential links between circadian clock dysregulation and SARS-CoV-2 infection susceptibility, disease presentation and progression, and clinical outcomes. Further research in this area may contribute towards novel circadian-centred prognostic, diagnostic and therapeutic approaches for COVID-19 in the era of precision health.
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Affiliation(s)
- Silvana Papagerakis
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Surgery, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Division of Biomedical EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Biochemistry, Microbiology and Immunology, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Otolaryngology – Head and Neck Surgery, Medical SchoolThe University of MichiganAnn ArborMichiganUSA
| | - Raed Said
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Surgery, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Laboratory of Precision Oral Health and Chronobiology, College of DentistryUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Anatomy, Physiology and Pharmacology, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Farinaz Ketabat
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Division of Biomedical EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Razi Mahmood
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Surgery, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Laboratory of Precision Oral Health and Chronobiology, College of DentistryUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Meenakshi Pundir
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Division of Biomedical EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Laboratory of Precision Oral Health and Chronobiology, College of DentistryUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Liubov Lobanova
- Laboratory of Precision Oral Health and Chronobiology, College of DentistryUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Greg Guenther
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Giuseppe Pannone
- Anatomic Pathology Unit, Department of Clinic and Experimental MedicineUniversity of FoggiaFoggiaItaly
| | - Kerry Lavender
- Department of Biochemistry, Microbiology and Immunology, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Blake R. McAlpin
- Laboratories of Neuroimmunology, Department of Symptom Research, Division of Internal MedicineThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Alain Moreau
- Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal DiseasesCentre Hospitalier Universitaire (CHU) Sainte‐Justine Research CenterMontrealQuebecCanada,Department of Stomatology, Faculty of Dentistry and Department of Biochemistry and Molecular Medicine, Faculty of MedicineUniversité de MontréalMontrealQuebecCanada
| | - Xiongbiao Chen
- Division of Biomedical EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Mechanical Engineering, School of EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Petros Papagerakis
- Division of Biomedical EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Laboratory of Precision Oral Health and Chronobiology, College of DentistryUniversity of SaskatchewanSaskatoonSaskatchewanCanada
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21
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Le Sage EH, Diamond M, Crespi EJ. Ranavirus infection-induced avoidance behaviour in wood frog juveniles: do amphibians socially distance? Biol Lett 2022; 18:20220359. [PMID: 36259234 PMCID: PMC9579918 DOI: 10.1098/rsbl.2022.0359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 09/29/2022] [Indexed: 11/12/2022] Open
Abstract
Hosts may limit exposure to pathogens through changes in behaviour, such as avoiding infected individuals or contaminated areas. Here, we tested for a behavioural response to ranavirus infection in juvenile wood frogs (Rana sylvatica) because the majority of dispersal between populations occurs during this life stage. We hypothesized that if infections are transmissible and detectable at this life stage, then susceptibles would display avoidance behaviours when introduced to an infected conspecific. Despite no apparent signs of infection, we observed a greater distance between susceptible-infected pairs, compared to pairs of either two infected or two susceptible animals. Further, distances between susceptible-infected pairs were positively related to the infection intensity of the focal exposed frog, suggesting the cue to avoid infected conspecifics may become more detectable with more intense infections. Although we did not quantify whether the transmission was affected by their distancing, our findings suggest that juvenile frogs have the potential to reduce terrestrial transmission of ranaviruses through avoidance behaviours.
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Affiliation(s)
- E. H. Le Sage
- School of Biological Sciences, Washington State University, PO Box 644236, Pullman, WA 99164-4236, USA
| | - M. Diamond
- School of Biological Sciences, Washington State University, PO Box 644236, Pullman, WA 99164-4236, USA
| | - E. J. Crespi
- School of Biological Sciences, Washington State University, PO Box 644236, Pullman, WA 99164-4236, USA
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22
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Skrlec I, Talapko J. Hepatitis B and circadian rhythm of the liver. World J Gastroenterol 2022; 28:3282-3296. [PMID: 36158265 PMCID: PMC9346465 DOI: 10.3748/wjg.v28.i27.3282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/15/2022] [Accepted: 06/13/2022] [Indexed: 02/06/2023] Open
Abstract
The circadian rhythm in humans is determined by the central clock located in the hypothalamus's suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus's life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.
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Affiliation(s)
- Ivana Skrlec
- Department of Biophysics, Biology, and Chemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia
| | - Jasminka Talapko
- Department of Anatomy Histology, Embryology, Pathology Anatomy and Pathology Histology, Faculty of Dental Medicine and Health, Osijek 31000, Croatia
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23
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Blanco JR, Verdugo-Sivianes EM, Amiama A, Muñoz-Galván S. The circadian rhythm of viruses and its implications on susceptibility to infection. Expert Rev Anti Infect Ther 2022; 20:1109-1117. [PMID: 35546444 DOI: 10.1080/14787210.2022.2072296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Circadian genes have an impact on multiple hormonal, metabolic, and immunological pathways and have recently been implicated in some infectious diseases. AREAS COVERED We review aspects related to the current knowledge about circadian rhythm and viral infections, their consequences, and the potential therapeutic options. EXPERT OPINION Expert opinion: In order to address a problem, it is necessary to know the topic in depth. Although in recent years there has been a growing interest in the role of circadian rhythms, many relevant questions remain to be resolved. Thus, the mechanisms linking the circadian machinery against viral infections are poorly understood. In a clear approach to personalized precision medicine, in order to treat a disease in the most appropriate phase of the circadian rhythm, and in order to achieve the optimal efficacy, it is highly recommended to carry out studies that improve the knowledge about the circadian rhythm.
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Affiliation(s)
- José-Ramon Blanco
- Servicio de Enfermedades Infecciosas, Hospital Universitario San Pedro, Logroño, Spain.,Centro de Investigación Biomédica de La Rioja (CIBIR), Logroño, Spain
| | - Eva M Verdugo-Sivianes
- Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Consejo Superior de Investigaciones Científicas, Sevilla, Spain.,CIBERONC, Instituto de Salud Carlos III, Madrid, Spain
| | - Ana Amiama
- Centro de Investigación Biomédica de La Rioja (CIBIR), Logroño, Spain
| | - Sandra Muñoz-Galván
- Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Consejo Superior de Investigaciones Científicas, Sevilla, Spain.,CIBERONC, Instituto de Salud Carlos III, Madrid, Spain
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24
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Espinosa-Salinas I, Colmenarejo G, Fernández-Díaz CM, Gómez de Cedrón M, Martinez JA, Reglero G, Ramírez de Molina A. Potential protective effect against SARS-CoV-2 infection by APOE rs7412 polymorphism. Sci Rep 2022; 12:7247. [PMID: 35508522 PMCID: PMC9065660 DOI: 10.1038/s41598-022-10923-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 04/04/2022] [Indexed: 01/08/2023] Open
Abstract
The pandemic burden caused by the SARS-CoV-2 coronavirus constitutes a global public health emergency. Increasing understanding about predisposing factors to infection and severity is now a priority. Genetic, metabolic, and environmental factors can play a crucial role in the course and clinical outcome of COVID-19. We aimed to investigate the putative relationship between genetic factors associated to obesity, metabolism and lifestyle, and the presence and severity of SARS-CoV-2 infection. A total of 249 volunteers (178 women and 71 men, with mean and ± SD age of 49 ± 11 years) characterized for dietary, lifestyle habits and anthropometry, were studied for presence and severity of COVID-19 infection, and genotyped for 26 genetic variants related to obesity, lipid profile, inflammation, and biorhythm patterns. A statistically significant association was found concerning a protective effect of APOE rs7412 against SARS-CoV-2 infection (p = 0.039; OR 0.216; CI 0.084, 0.557) after correction for multiple comparisons. This protective effect was also ascribed to the APOɛ2 allele (p = 0.001; OR 0.207; CI 0.0796, 0.538). The genetic variant rs7412 resulting in ApoE2, genetic determinant of lipid and lipoprotein levels, could play a significant role protecting against SARS-CoV-2 infection.
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Affiliation(s)
| | | | | | | | - J Alfredo Martinez
- IMDEA-Food Institute, CEI UAM+CSIC, 28049, Madrid, Spain.,Center for Nutrition Research (CIN), Navarra Institute for Health Research (IdiSNA), 31008, Pamplona, Spain.,Center of Biomedical Research in Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029, Madrid, Spain
| | - Guillermo Reglero
- IMDEA-Food Institute, CEI UAM+CSIC, 28049, Madrid, Spain.,Institute of Food Science Research (CIAL), CEI UAM+CSIC, 28049, Madrid, Spain
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25
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Mayer C, Tyler J, Fang Y, Flora C, Frank E, Tewari M, Choi SW, Sen S, Forger DB. Consumer-grade wearables identify changes in multiple physiological systems during COVID-19 disease progression. Cell Rep Med 2022; 3:100601. [PMID: 35480626 PMCID: PMC9017023 DOI: 10.1016/j.xcrm.2022.100601] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 11/04/2021] [Accepted: 03/20/2022] [Indexed: 11/29/2022]
Abstract
Consumer-grade wearables are needed to track disease, especially in the ongoing pandemic, as they can monitor patients in real time. We show that decomposing heart rate from low-cost wearable technologies into signals from different systems can give a multidimensional description of physiological changes due to COVID-19 infection. We find that the separate physiological features of basal heart rate, heart rate response to physical activity, circadian variation in heart rate, and autocorrelation of heart rate are significantly altered and can classify symptomatic versus healthy periods. Increased heart rate and autocorrelation begin at symptom onset, while the heart rate response to activity increases soon after symptom onset and increases more in individuals exhibiting cough. Symptom onset is associated with a blunting of circadian variation in heart rate, as measured by the uncertainty in the phase estimate. This work establishes an innovative data analytic approach to monitor disease progression remotely using consumer-grade wearables.
We separate wearable heart rate into cardiopulmonary, circadian, and other signals Parameters from different physiological systems enable disease tracking Individual signals change in distinct ways around COVID-19 symptom onset Together, the parameter changes can distinguish healthy from infection periods
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Affiliation(s)
- Caleb Mayer
- Department of Mathematics, University of Michigan, Ann Arbor, MI 48109, USA
| | - Jonathan Tyler
- Department of Mathematics, University of Michigan, Ann Arbor, MI 48109, USA.,Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA
| | - Yu Fang
- Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA
| | - Christopher Flora
- Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Elena Frank
- Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA
| | - Muneesh Tewari
- Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.,Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.,Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
| | - Sung Won Choi
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.,Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
| | - Srijan Sen
- Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA
| | - Daniel B Forger
- Department of Mathematics, University of Michigan, Ann Arbor, MI 48109, USA.,Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
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26
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Mohd Fuad SH, Juliana N, Mohd Azmi NAS, Mohd Fahmi Teng NI, Azmani S, Abu IF, Das S. Circadian Disruption and Occupational Toxicants Exposure Affecting the Immunity of Shift Workers During SARS CoV-2 Pandemic. Front Public Health 2022; 10:829013. [PMID: 35392476 PMCID: PMC8980348 DOI: 10.3389/fpubh.2022.829013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 02/21/2022] [Indexed: 11/13/2022] Open
Abstract
In several regions of the world, the recent Coronavirus Disease-2019 (COVID-19) pandemic outbreak increased morbidity and mortality. The pandemic situation disrupted many workers' previously established lifestyles. The main aim of the present review was to describe the circadian disruption and occupational toxicant exposure affecting the immunity of shift workers during the SARS CoV-2 pandemic. We retrieved pertinent published literature from the Google Scholar, PubMed, and Scopus databases. In the present review, we discuss the circadian rhythm involving the hypothalamic-pituitary-adrenal (HPA) axis at the molecular level, its disruption, occupational toxicant exposure causing immunomodulatory effects, and the role of immunity during the SARS CoV-2 pandemic. The severity of the progression of the viral infection depends on multiple factors affecting immunity. Hence, shift workers may need to be aware of those factors such as circadian rhythm disruption as well as occupational toxicant exposure. The timing of shift workers' energy intake is also important concerning the shift of the workers. The information in the present review may be important for all workers who are at risk during the pandemic. In the absence of any published literature related to association of circadian rhythm disruption with occupational toxicant exposure, the present review may have greater importance.
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Affiliation(s)
- Siti Hanisah Mohd Fuad
- Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Malaysia
| | - Norsham Juliana
- Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Malaysia
| | | | | | - Sahar Azmani
- Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Malaysia
| | - Izuddin Fahmy Abu
- Institute of Medical Science Technology, Universiti Kuala Lumpur, Kajang, Malaysia
| | - Srijit Das
- Department of Human & Clinical Anatomy, College of Medicine and Health Sciences, Muscat, Oman
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27
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Rafferty H, Murray MJ, Tam JCH, Macfarlane A, Smith C, Lumley SF, Atabani S, McKeating JA, Sharma D, Reeves M, Whitmore D, Griffiths P. Are the Patterns of Cytomegalovirus Viral Load Seen After Solid Organ Transplantation Affected by Circadian Rhythm? J Infect Dis 2022; 226:357-365. [PMID: 35184187 PMCID: PMC9400432 DOI: 10.1093/infdis/jiac055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 02/16/2022] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) is an important opportunistic pathogen after transplantation. Some virological variation in transplant recipients is explained by donor and recipient CMV serostatus, but not all. Circadian variability of herpesviruses has been described, so we investigated the effect of time of day of transplantation on posttransplant CMV viremia. METHODS We performed a retrospective analysis of 1517 patients receiving liver or kidney allografts at a single center from 2002 to 2018. All patients were given preemptive therapy with CMV viremia monitoring after transplantation. Circulatory arrest and reperfusion time of donor organ were categorized into 4 periods. Patients were divided into serostatus groups based on previous CMV infection in donor and recipient. CMV viremia parameters were compared between time categories for each group. Factor analysis of mixed data was used to interrogate this complex data set. RESULTS Live-donor transplant recipients were less likely to develop viremia than recipients of deceased-donor organs (48% vs 61%; P < .001). After controlling for this, there was no evidence of time of day of transplantation affecting CMV parameters in any serostatus group, by logistic regression or factor analysis of mixed data. DISCUSSION We found no evidence for a circadian effect of transplantation on CMV viremia, but these novel results warrant confirmation by other centers.
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Affiliation(s)
- Hannah Rafferty
- Correspondence: Hannah Rafferty, Institute for Immunity and Transplantation, Royal Free Hospital, Pond Street, London, NW3 2QG, United Kingdom ()
| | - Matthew J Murray
- Institute for Immunity and Transplantation, UCL, London, United Kingdom
| | - Jerry C H Tam
- Institute for Immunity and Transplantation, UCL, London, United Kingdom
| | | | - Colette Smith
- Institute for Global Health, University College London, London, United Kingdom
| | - Sheila F Lumley
- Institute for Immunity and Transplantation, UCL, London, United Kingdom,Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Sowsan Atabani
- Public Health England Birmingham Laboratory, National Infection Service, University Hospitals Birmingham, Bordesley Green East, BirminghamUnited Kingdom
| | - Jane A McKeating
- Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom,Chinese Academy of Medical Sciences, Oxford Institute (COI), University of Oxford, United Kingdom
| | - Dinesh Sharma
- Surgery Department, Royal Free Hospital, London, United Kingdom
| | - Matthew Reeves
- Institute for Immunity and Transplantation, UCL, London, United Kingdom
| | - David Whitmore
- Department of Cell and Developmental Biology, University College London, London, United Kingdom
| | - Paul Griffiths
- Institute for Immunity and Transplantation, UCL, London, United Kingdom
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28
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Ebersole JL, Gonzalez OA. Mucosal circadian rhythm pathway genes altered by aging and periodontitis. PLoS One 2022; 17:e0275199. [PMID: 36472983 PMCID: PMC9725147 DOI: 10.1371/journal.pone.0275199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 09/12/2022] [Indexed: 12/12/2022] Open
Abstract
As circadian processes can impact the immune system and are affected by infections and inflammation, this study examined the expression of circadian rhythm genes in periodontitis. METHODS Macaca mulatta were used with naturally-occurring and ligature-induced periodontitis. Gingival tissue samples were obtained from healthy, diseased, and resolved sites in four groups: young (≤3 years), adolescent (3-7 years), adult (12-26) and aged (18-23 years). Microarrays targeted circadian rhythm (n = 42), inflammation/tissue destruction (n = 11), bone biology (n = 8) and hypoxia pathway (n = 7) genes. RESULTS The expression of many circadian rhythm genes, across functional components of the pathway, was decreased in healthy tissues from younger and aged animals, as well as showing significant decreases with periodontitis. Negative correlations of the circadian rhythm gene levels with inflammatory mediators and tissue destructive/remodeling genes were particularly accentuated in disease. A dominance of positive correlations with hypoxia genes was observed, except HIF1A, that was uniformly negatively correlated in health, disease and resolution. CONCLUSIONS The chronic inflammation of periodontitis exhibits an alteration of the circadian rhythm pathway, predominantly via decreased gene expression. Thus, variation in disease expression and the underlying molecular mechanisms of disease may be altered due to changes in regulation of the circadian rhythm pathway functions.
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Affiliation(s)
- Jeffrey L. Ebersole
- Department of Biomedical Sciences, School of Dental Medicine, University of Nevada Las Vegas, Nevada, Nevada Las Vegas
- * E-mail:
| | - Octavio A. Gonzalez
- Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, Kentucky
- Division of Periodontology, College of Dentistry, University of Kentucky, Lexington, Kentucky
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29
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Stern J, Solomon A, Dantanarayana A, Pascoe R, Reynaldi A, Davenport MP, Milush J, Deeks SG, Hartogensis W, Hecht FM, Cockerham L, Roche M, Lewin SR. Cell-associated HIV RNA has a Circadian Cycle in Males Living with HIV on Antiretroviral Therapy. J Infect Dis 2021; 225:1721-1730. [PMID: 34655216 DOI: 10.1093/infdis/jiab533] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 10/15/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Circadian transcription factors that regulate cell-autonomous circadian clocks can also increase HIV transcription in vitro. We aimed to determine if circadian variation in HIV transcription exists in people living with HIV (PLHIV) on antiretroviral therapy (ART). METHODS We performed a prospective observational study of male PLHIV on ART, sampling blood every four hours for 24 hours. Using qPCR, we quantified expression of circadian associated genes, HIV DNA and cell-associated unspliced (CA-US) RNA in peripheral blood CD4+ T-cells. Plasma sex hormones were quantified alongside plasma and salivary cortisol. The primary outcome was to identify temporal variations in CA-US HIV RNA using a linear mixed effect regression framework and maximum likelihood estimation. RESULTS Salivary and plasma cortisol, and circadian genes including Clock, Bmal1, and Per3 varied with a circadian rhythm. CA-US HIV RNA and the ratio of CA-US HIV RNA-to-DNA in CD4+ T-cells also demonstrated circadian variations, with no variation in HIV DNA. Circulating oestradiol was highly predictive of CA-US HIV RNA variation in vivo. CONCLUSION CA-US HIV RNA in PLHIV on ART varies temporally with a circadian rhythm. These findings have implications for the design of clinical trials and biomarkers to assess HIV cure interventions.
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Affiliation(s)
- Jared Stern
- The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia
| | - Ajantha Solomon
- The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia
| | - Ashanti Dantanarayana
- The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia
| | - Rachel Pascoe
- The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia
| | - Arnold Reynaldi
- The Kirby Institute, University of New South Wales, Sydney, Australia
| | - Miles P Davenport
- The Kirby Institute, University of New South Wales, Sydney, Australia
| | - Jeffrey Milush
- Department of Medicine, University of California, San Francisco, USA
| | - Steven G Deeks
- Department of Medicine, University of California, San Francisco, USA
| | - Wendy Hartogensis
- Osher Center for Integrative Medicine, University of California San Francisco, San Francisco, USA
| | - Frederick M Hecht
- Osher Center for Integrative Medicine, University of California San Francisco, San Francisco, USA
| | - Leslie Cockerham
- Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee, USA
| | - Michael Roche
- The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia
| | - Sharon R Lewin
- The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia.,Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia
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30
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Maiese K. Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm. FRONT BIOSCI-LANDMRK 2021; 26:614-627. [PMID: 34590471 PMCID: PMC8756734 DOI: 10.52586/4971] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 07/26/2021] [Accepted: 08/10/2021] [Indexed: 11/23/2022]
Abstract
Introduction: Dementia and cognitive loss impact a significant proportion of the global population and present almost insurmountable challenges for treatment since they stem from multifactorial etiologies. Innovative avenues for treatment are highly warranted. Methods and results: Novel work with biological clock genes that oversee circadian rhythm may meet this critical need by focusing upon the pathways of the mechanistic target of rapamycin (mTOR), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), mammalian forkhead transcription factors (FoxOs), the growth factor erythropoietin (EPO), and the wingless Wnt pathway. These pathways are complex in nature, intimately associated with autophagy that can maintain circadian rhythm, and have an intricate relationship that can lead to beneficial outcomes that may offer neuroprotection, metabolic homeostasis, and prevention of cognitive loss. However, biological clocks and alterations in circadian rhythm also have the potential to lead to devastating effects involving tumorigenesis in conjunction with pathways involving Wnt that oversee angiogenesis and stem cell proliferation. Conclusions: Current work with biological clocks and circadian rhythm pathways provide exciting possibilities for the treating dementia and cognitive loss, but also provide powerful arguments to further comprehend the intimate and complex relationship among these pathways to fully potentiate desired clinical outcomes.
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Affiliation(s)
- Kenneth Maiese
- Cellular and Molecular Signaling, New York, NY 10022, USA
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31
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Maiese K. Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways. Biomolecules 2021; 11:1002. [PMID: 34356626 PMCID: PMC8301848 DOI: 10.3390/biom11071002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/05/2021] [Accepted: 07/07/2021] [Indexed: 01/18/2023] Open
Abstract
Neurodegenerative disorders affect fifteen percent of the world's population and pose a significant financial burden to all nations. Cognitive impairment is the seventh leading cause of death throughout the globe. Given the enormous challenges to treat cognitive disorders, such as Alzheimer's disease, and the inability to markedly limit disease progression, circadian clock gene pathways offer an exciting strategy to address cognitive loss. Alterations in circadian clock genes can result in age-related motor deficits, affect treatment regimens with neurodegenerative disorders, and lead to the onset and progression of dementia. Interestingly, circadian pathways hold an intricate relationship with autophagy, the mechanistic target of rapamycin (mTOR), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), mammalian forkhead transcription factors (FoxOs), and the trophic factor erythropoietin. Autophagy induction is necessary to maintain circadian rhythm homeostasis and limit cortical neurodegenerative disease, but requires a fine balance in biological activity to foster proper circadian clock gene regulation that is intimately dependent upon mTOR, SIRT1, FoxOs, and growth factor expression. Circadian rhythm mechanisms offer innovative prospects for the development of new avenues to comprehend the underlying mechanisms of cognitive loss and forge ahead with new therapeutics for dementia that can offer effective clinical treatments.
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Affiliation(s)
- Kenneth Maiese
- Cellular and Molecular Signaling, New York, NY 10022, USA
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32
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Williams SJ, Meadows R, Coveney CM. Desynchronised times? Chronobiology, (bio)medicalisation and the rhythms of life itself. SOCIOLOGY OF HEALTH & ILLNESS 2021; 43:1501-1517. [PMID: 34254324 DOI: 10.1111/1467-9566.13324] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 04/26/2021] [Accepted: 06/07/2021] [Indexed: 06/13/2023]
Abstract
This paper takes a critical look at the role of chronobiology in society today, with particular reference to its entanglements with health and medicine and whether or not this amounts to the (bio)medicalisation of our bodily rhythms. What we have here, we show, is a complex unfolding storyline, within and beyond medicine. On the one hand, the promises and problems of these circadian, infradian and ultradian rhythms for our health and well-being are now increasingly emphasised. On the other hand, a variety of new rhythmic interventions and forms of governance are now emerging within and beyond medicine, from chronotherapies and chronopharmacology to biocompatible school and work schedules, and from chronodiets to the optimisation of all we do according to our 'chronotypes'. Conceptualising these developments, we suggest challenges us to think within and beyond medicalisation to wider processes of biomedicalisation and the biopolitics of our body clocks: a vital new strand of chronopolitics today indeed which implicates us all in sickness and in health as the very embodiment of these rhythms of life itself. The paper concludes with a call for further research on these complex unfolding relations between chronobiology, health and society in these desynchronised times of ours.
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Affiliation(s)
| | - Robert Meadows
- Department of Sociology, University of Surrey, Surrey, UK
| | - Catherine M Coveney
- Social and Policy Studies, School of Social Sciences and Humanities, Loughborough University, London, UK
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Giri A, Srinivasan A, Sundar IK. COVID-19: Sleep, Circadian Rhythms and Immunity - Repurposing Drugs and Chronotherapeutics for SARS-CoV-2. Front Neurosci 2021; 15:674204. [PMID: 34220430 PMCID: PMC8249936 DOI: 10.3389/fnins.2021.674204] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 05/05/2021] [Indexed: 01/08/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected nearly 28 million people in the United States and has caused more than five hundred thousand deaths as of February 21, 2021. As the novel coronavirus continues to take its toll in the United States and all across the globe, particularly among the elderly (>65 years), clinicians and translational researchers are taking a closer look at the nexus of sleep, circadian rhythms and immunity that may contribute toward a more severe coronavirus disease-19 (COVID-19). SARS-CoV-2-induced multi-organ failure affects both central and peripheral organs, causing increased mortality in the elderly. However, whether differences in sleep, circadian rhythms, and immunity between older and younger individuals contribute to the age-related differences in systemic dysregulation of target organs observed in SARS-CoV-2 infection remain largely unknown. Current literature demonstrates the emerging role of sleep, circadian rhythms, and immunity in the development of chronic pulmonary diseases and respiratory infections in human and mouse models. The exact mechanism underlying acute respiratory distress syndrome (ARDS) and other cardiopulmonary complications in elderly patients in combination with associated comorbidities remain unclear. Nevertheless, understanding the critical role of sleep, circadian clock dysfunction in target organs, and immune status of patients with SARS-CoV-2 may provide novel insights into possible therapies. Chronotherapy is an emerging concept that is gaining attention in sleep medicine. Accumulating evidence suggests that nearly half of all physiological functions follow a strict daily rhythm. However, healthcare professionals rarely take implementing timed-administration of drugs into consideration. In this review, we summarize recent findings directly relating to the contributing roles of sleep, circadian rhythms and immune response in modulating infectious disease processes, and integrate chronotherapy in the discussion of the potential drugs that can be repurposed to improve the treatment and management of COVID-19.
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Affiliation(s)
| | | | - Isaac Kirubakaran Sundar
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, United States
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Sultan A, Ali R, Sultan T, Ali S, Khan NJ, Parganiha A. Circadian clock modulating small molecules repurposing as inhibitors of SARS-CoV-2 M pro for pharmacological interventions in COVID-19 pandemic. Chronobiol Int 2021; 38:971-985. [PMID: 33820462 PMCID: PMC8022342 DOI: 10.1080/07420528.2021.1903027] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The COVID-19 pandemic caused by SARS-CoV-2 is a global health emergency warranting the development of targeted treatment. The main protease Mpro is considered as a key drug target in coronavirus infections because of its vital role in the proteolytic processing of two essential polyproteins required for the replication and transcription of viral RNA. Targeting and inhibiting the Mpro activity represents a valid approach to prevent the SARS-CoV-2 replication and spread. Based on the structure-assisted drug designing, here we report a circadian clock-modulating small molecule “SRT2183” as a potent inhibitor of Mpro to block the replication of SARS-CoV-2. The findings are expected to pave the way for the development of therapeutics for COVID-19.
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Affiliation(s)
- Armiya Sultan
- Functional Genomics Laboratory, Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia (A Central University), New Delhi, India.,Department of Biosciences, Jamia Millia Islamia (A Central University), New Delhi, India.,Chronobiology and Animal Behaviour Laboratory, School of Studies in Life Sciences, Pt. Ravishankar Shukla University, Raipur, India
| | - Rafat Ali
- Department of Biosciences, Jamia Millia Islamia (A Central University), New Delhi, India
| | - Tahira Sultan
- Department of Biochemistry, University of Kashmir, Srinagar, India
| | - Sher Ali
- Department of Life Sciences, Sharda University, Greater Noida, India
| | - Nida Jamil Khan
- Department of Biosciences, Jamia Millia Islamia (A Central University), New Delhi, India
| | - Arti Parganiha
- Chronobiology and Animal Behaviour Laboratory, School of Studies in Life Sciences, Pt. Ravishankar Shukla University, Raipur, India
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Gaspar LS, Hesse J, Yalçin M, Santos B, Carvalhas-Almeida C, Ferreira M, Moita J, Relógio A, Cavadas C, Álvaro AR. Long-term continuous positive airway pressure treatment ameliorates biological clock disruptions in obstructive sleep apnea. EBioMedicine 2021; 65:103248. [PMID: 33647771 PMCID: PMC7920825 DOI: 10.1016/j.ebiom.2021.103248] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 02/01/2021] [Accepted: 02/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Obstructive Sleep Apnea (OSA) is a highly prevalent and underdiagnosed sleep disorder. Recent studies suggest that OSA might disrupt the biological clock, potentially causing or worsening OSA-associated comorbidities. However, the effect of OSA treatment on clock disruption is not fully understood. METHODS The impact of OSA and short- (four months) and long-term (two years) OSA treatment, with Continuous Positive Airway Pressure (CPAP), on the biological clock was investigated at four time points within 24 h, in OSA patients relative to controls subjects (no OSA) of the same sex and age group, in a case-control study. Plasma melatonin and cortisol, body temperature and the expression levels and rhythmicity of eleven clock genes in peripheral blood mononuclear cells (PBMCs) were assessed. Additional computational tools were used for a detailed data analysis. FINDINGS OSA impacts on clock outputs and on the expression of several clock genes in PBMCs. Neither short- nor long-term treatment fully reverted OSA-induced alterations in the expression of clock genes. However, long-term treatment was able to re-establish levels of plasma melatonin and cortisol and body temperature. Machine learning methods could discriminate controls from untreated OSA patients. Following long-term treatment, the distinction between controls and patients disappeared, suggesting a closer similarity of the phenotypes. INTERPRETATION OSA alters biological clock-related characteristics that differentially respond to short- and long-term CPAP treatment. Long-term CPAP was more efficient in counteracting OSA impact on the clock, but the obtained results suggest that it is not fully effective. A better understanding of the impact of OSA and OSA treatment on the clock may open new avenues to OSA diagnosis, monitoring and treatment.
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Affiliation(s)
- Laetitia S Gaspar
- Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, Pólo I, Coimbra 3004-504, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; PhD Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal
| | - Janina Hesse
- Institute for Theoretical Biology (ITB), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany; Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumour Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany; Department of Human Medicine, Institute for Systems Medicine and Bioinformatics, MSH Medical School Hamburg-University of Applied Sciences and Medical University, Am Kaiserkai 1, Hamburg 20457, Germany
| | - Müge Yalçin
- Institute for Theoretical Biology (ITB), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany; Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumour Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany
| | - Bárbara Santos
- Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, Pólo I, Coimbra 3004-504, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal
| | - Catarina Carvalhas-Almeida
- Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, Pólo I, Coimbra 3004-504, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal
| | - Mafalda Ferreira
- Sleep Medicine Centre, Coimbra Hospital and University Centre, Coimbra, Portugal
| | - Joaquim Moita
- Sleep Medicine Centre, Coimbra Hospital and University Centre, Coimbra, Portugal
| | - Angela Relógio
- Institute for Theoretical Biology (ITB), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany; Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumour Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany; Department of Human Medicine, Institute for Systems Medicine and Bioinformatics, MSH Medical School Hamburg-University of Applied Sciences and Medical University, Am Kaiserkai 1, Hamburg 20457, Germany.
| | - Cláudia Cavadas
- Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, Pólo I, Coimbra 3004-504, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
| | - Ana Rita Álvaro
- Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, Pólo I, Coimbra 3004-504, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal.
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Narasimamurthy R, Virshup DM. The phosphorylation switch that regulates ticking of the circadian clock. Mol Cell 2021; 81:1133-1146. [PMID: 33545069 DOI: 10.1016/j.molcel.2021.01.006] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 12/18/2020] [Accepted: 01/05/2021] [Indexed: 02/08/2023]
Abstract
In our 24/7 well-lit world, it's easy to skip or delay sleep to work, study, and play. However, our circadian rhythms are not easily fooled; the consequences of jet lag and shift work are many and severe, including metabolic, mood, and malignant disorders. The internal clock that keeps track of time has at its heart the reversible phosphorylation of the PERIOD proteins, regulated by isoforms of casein kinase 1 (CK1). In-depth biochemical, genetic, and structural studies of these kinases, their mutants, and their splice variants have combined over the past several years to provide a robust understanding of how the core clock is regulated by a phosphoswitch whereby phosphorylation of a stabilizing site on PER blocks phosphorylation of a distant phosphodegron. The recent structure of a circadian mutant form of CK1 implicates an internal activation loop switch that regulates this phosphoswitch and points to new approaches to regulation of the clock.
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Affiliation(s)
- Rajesh Narasimamurthy
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore.
| | - David M Virshup
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
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Abstract
The circadian clock controls several aspects of mammalian physiology and orchestrates the daily oscillations of biological processes and behavior. Our circadian rhythms are driven by an endogenous central clock in the brain that synchronizes with clocks in peripheral tissues, thereby regulating our immune system and the severity of infections. These rhythms affect the pharmacokinetics and efficacy of therapeutic agents and vaccines. The core circadian regulatory circuits and clock-regulated host pathways provide fertile ground to identify novel antiviral therapies. An increased understanding of the role circadian systems play in regulating virus infection and the host response to the virus will inform our clinical management of these diseases. This review provides an overview of the experimental and clinical evidence reporting on the interplay between the circadian clock and viral infections, highlighting the importance of virus-clock research.
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Affiliation(s)
- Helene Borrmann
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
| | | | - Xiaodong Zhuang
- Xiaodong Zhuang, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7FZ, UK; e-mail:
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38
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Xavier LL, Neves PFR, Paz LV, Neves LT, Bagatini PB, Timmers LFSM, Rasia-Filho AA, Mestriner RG, Wieck A. Does Angiotensin II Peak in Response to SARS-CoV-2? Front Immunol 2021; 11:577875. [PMID: 33519802 PMCID: PMC7842149 DOI: 10.3389/fimmu.2020.577875] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 12/04/2020] [Indexed: 12/18/2022] Open
Abstract
Human infection by the SARS-CoV-2 is causing the current COVID-19 pandemic. With the growing numbers of cases and deaths, there is an urgent need to explore pathophysiological hypotheses in an attempt to better understand the factors determining the course of the disease. Here, we hypothesize that COVID-19 severity and its symptoms could be related to transmembrane and soluble Angiotensin-converting enzyme 2 (tACE2 and sACE2); Angiotensin II (ANG II); Angiotensin 1-7 (ANG 1-7) and angiotensin receptor 1 (AT1R) activation levels. Additionally, we hypothesize that an early peak in ANG II and ADAM-17 might represent a physiological attempt to reduce viral infection via tACE2. This viewpoint presents: (1) a brief introduction regarding the renin-angiotensin-aldosterone system (RAAS), detailing its receptors, molecular synthesis, and degradation routes; (2) a description of the proposed early changes in the RAAS in response to SARS-CoV-2 infection, including biological scenarios for the best and worst prognoses; and (3) the physiological pathways and reasoning for changes in the RAAS following SARS-CoV-2 infection.
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Affiliation(s)
- Léder Leal Xavier
- Laboratório de Biologia Celular e Tecidual, Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre, Brazil
| | - Paula Fernanda Ribas Neves
- Laboratório de Biologia Celular e Tecidual, Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre, Brazil
| | - Lisiê Valeria Paz
- Laboratório de Biologia Celular e Tecidual, Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre, Brazil
| | - Laura Tartari Neves
- Laboratório de Biologia Celular e Tecidual, Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre, Brazil
| | - Pamela Brambilla Bagatini
- Laboratório de Biologia Celular e Tecidual, Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre, Brazil
| | - Luís Fernando Saraiva Macedo Timmers
- Programa de Pós-Graduação em Biotecnologia (PPGBiotec), Programa de Pós-Graduação em Ciências Médicas (PPGCM), Universidade do Vale do Taquari-UNIVATES, Lajeado, Brazil
| | - Alberto Antônio Rasia-Filho
- Departamento de Ciências Básicas da Saúde/Fisiologia, Universidade Federal de Ciências da Saúde de Porto Alegre-UFCSPA, Porto Alegre, Brazil
| | - Régis Gemerasca Mestriner
- Laboratório de Biologia Celular e Tecidual, Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre, Brazil
| | - Andrea Wieck
- Laboratório de Biologia Celular e Tecidual, Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre, Brazil
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Fernandes J, Miranda RL, de Lemos ERS, Guterres A. MicroRNAs and Mammarenaviruses: Modulating Cellular Metabolism. Cells 2020; 9:E2525. [PMID: 33238430 PMCID: PMC7709035 DOI: 10.3390/cells9112525] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/04/2020] [Accepted: 11/11/2020] [Indexed: 12/11/2022] Open
Abstract
Mammarenaviruses are a diverse genus of emerging viruses that include several causative agents of severe viral hemorrhagic fevers with high mortality in humans. Although these viruses share many similarities, important differences with regard to pathogenicity, type of immune response, and molecular mechanisms during virus infection are different between and within New World and Old World viral infections. Viruses rely exclusively on the host cellular machinery to translate their genome, and therefore to replicate and propagate. miRNAs are the crucial factor in diverse biological processes such as antiviral defense, oncogenesis, and cell development. The viral infection can exert a profound impact on the cellular miRNA expression profile, and numerous RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Our present study indicates that mammarenavirus infection induces metabolic reprogramming of host cells, probably manipulating cellular microRNAs. A number of metabolic pathways, including valine, leucine, and isoleucine biosynthesis, d-Glutamine and d-glutamate metabolism, thiamine metabolism, and pools of several amino acids were impacted by the predicted miRNAs that would no longer regulate these pathways. A deeper understanding of mechanisms by which mammarenaviruses handle these signaling pathways is critical for understanding the virus/host interactions and potential diagnostic and therapeutic targets, through the inhibition of specific pathologic metabolic pathways.
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Affiliation(s)
- Jorlan Fernandes
- Hantaviruses and Rickettsiosis Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil;
| | - Renan Lyra Miranda
- Neurochemistry Interactions Laboratory, Universidade Federal Fluminense, Niterói 24020-150, Brazil;
| | - Elba Regina Sampaio de Lemos
- Hantaviruses and Rickettsiosis Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil;
| | - Alexandro Guterres
- Hantaviruses and Rickettsiosis Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil;
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Hesse J, Malhan D, Yalҫin M, Aboumanify O, Basti A, Relógio A. An Optimal Time for Treatment-Predicting Circadian Time by Machine Learning and Mathematical Modelling. Cancers (Basel) 2020; 12:cancers12113103. [PMID: 33114254 PMCID: PMC7690897 DOI: 10.3390/cancers12113103] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 10/15/2020] [Accepted: 10/20/2020] [Indexed: 02/07/2023] Open
Abstract
Tailoring medical interventions to a particular patient and pathology has been termed personalized medicine. The outcome of cancer treatments is improved when the intervention is timed in accordance with the patient's internal time. Yet, one challenge of personalized medicine is how to consider the biological time of the patient. Prerequisite for this so-called chronotherapy is an accurate characterization of the internal circadian time of the patient. As an alternative to time-consuming measurements in a sleep-laboratory, recent studies in chronobiology predict circadian time by applying machine learning approaches and mathematical modelling to easier accessible observables such as gene expression. Embedding these results into the mathematical dynamics between clock and cancer in mammals, we review the precision of predictions and the potential usage with respect to cancer treatment and discuss whether the patient's internal time and circadian observables, may provide an additional indication for individualized treatment timing. Besides the health improvement, timing treatment may imply financial advantages, by ameliorating side effects of treatments, thus reducing costs. Summarizing the advances of recent years, this review brings together the current clinical standard for measuring biological time, the general assessment of circadian rhythmicity, the usage of rhythmic variables to predict biological time and models of circadian rhythmicity.
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Affiliation(s)
- Janina Hesse
- Institute for Theoretical Biology (ITB), Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany; (J.H.); (D.M.); (M.Y.); (O.A.); (A.B.)
- Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology and Tumor Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
| | - Deeksha Malhan
- Institute for Theoretical Biology (ITB), Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany; (J.H.); (D.M.); (M.Y.); (O.A.); (A.B.)
- Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology and Tumor Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
| | - Müge Yalҫin
- Institute for Theoretical Biology (ITB), Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany; (J.H.); (D.M.); (M.Y.); (O.A.); (A.B.)
- Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology and Tumor Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
| | - Ouda Aboumanify
- Institute for Theoretical Biology (ITB), Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany; (J.H.); (D.M.); (M.Y.); (O.A.); (A.B.)
- Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology and Tumor Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
| | - Alireza Basti
- Institute for Theoretical Biology (ITB), Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany; (J.H.); (D.M.); (M.Y.); (O.A.); (A.B.)
- Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology and Tumor Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
| | - Angela Relógio
- Institute for Theoretical Biology (ITB), Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany; (J.H.); (D.M.); (M.Y.); (O.A.); (A.B.)
- Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology and Tumor Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin Humboldt—Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
- Department of Human Medicine, Institute for Systems Medicine and Bioinformatics, MSH Medical School Hamburg—University of Applied Sciences and Medical University, 20457 Hamburg, Germany
- Correspondence: or
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Abstract
Circadian clocks control the function of our immune system, virus replication and the severity of infections. Our daily rhythms also regulate the pharmacokinetics and efficacy of several therapeutics. Consequently, better understanding of the effects of circadian biology on SARS-CoV-2 infection would improve the clinical management of COVID-19. Circadian clocks control our immune system, infections and pharmacokinetics. Ray and Reddy argue that better understanding the effects of circadian biology on SARS-CoV-2 infection would improve COVID-19 management.
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Affiliation(s)
- Sandipan Ray
- Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. .,Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
| | - Akhilesh B Reddy
- Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. .,Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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Borrmann H, Davies R, Dickinson M, Pedroza-Pacheco I, Schilling M, Vaughan-Jackson A, Magri A, James W, Balfe P, Borrow P, McKeating JA, Zhuang X. Pharmacological activation of the circadian component REV-ERB inhibits HIV-1 replication. Sci Rep 2020; 10:13271. [PMID: 32764708 PMCID: PMC7413328 DOI: 10.1038/s41598-020-70170-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 07/07/2020] [Indexed: 12/18/2022] Open
Abstract
Human immunodeficiency virus 1 (HIV-1) is a life-threatening pathogen that still lacks a curative therapy or vaccine. Despite the reduction in AIDS-related deaths achieved by current antiretroviral therapies, drawbacks including drug resistance and the failure to eradicate infection highlight the need to identify new pathways to target the infection. Circadian rhythms are endogenous 24-h oscillations which regulate physiological processes including immune responses to infection, and there is an emerging role for the circadian components in regulating viral replication. The molecular clock consists of transcriptional/translational feedback loops that generate rhythms. In mammals, BMAL1 and CLOCK activate rhythmic transcription of genes including the nuclear receptor REV-ERBα, which represses BMAL1 and plays an essential role in sustaining a functional clock. We investigated whether REV-ERB activity regulates HIV-1 replication and found REV-ERB agonists inhibited HIV-1 promoter activity in cell lines, primary human CD4 T cells and macrophages, whilst antagonism or genetic disruption of REV-ERB increased promoter activity. The REV-ERB agonist SR9009 inhibited promoter activity of diverse HIV-subtypes and HIV-1 replication in primary T cells. This study shows a role for REV-ERB synthetic agonists to inhibit HIV-1 LTR promoter activity and viral replication, supporting a role for circadian clock components in regulating HIV-1 replication.
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Affiliation(s)
- Helene Borrmann
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7FZ, UK
| | - Rhianna Davies
- Institute of Immunity and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK
| | - Matthew Dickinson
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7FZ, UK
| | | | - Mirjam Schilling
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7FZ, UK
| | | | - Andrea Magri
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7FZ, UK
| | - William James
- Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK
| | - Peter Balfe
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7FZ, UK
| | - Persephone Borrow
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7FZ, UK
| | - Jane A McKeating
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7FZ, UK
| | - Xiaodong Zhuang
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
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Shirazi J, Donzanti MJ, Nelson KM, Zurakowski R, Fromen CA, Gleghorn JP. Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Progression. Cell Mol Bioeng 2020; 13:259-284. [PMID: 32837585 PMCID: PMC7384395 DOI: 10.1007/s12195-020-00637-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 07/14/2020] [Indexed: 12/19/2022] Open
Abstract
COVID-19 is a disease that manifests itself in a multitude of ways across a wide range of tissues. Many factors are involved, and though impressive strides have been made in studying this novel disease in a very short time, there is still a great deal that is unknown about how the virus functions. Clinical data has been crucial for providing information on COVID-19 progression and determining risk factors. However, the mechanisms leading to the multi-tissue pathology are yet to be fully established. Although insights from SARS-CoV-1 and MERS-CoV have been valuable, it is clear that SARS-CoV-2 is different and merits its own extensive studies. In this review, we highlight unresolved questions surrounding this virus including the temporal immune dynamics, infection of non-pulmonary tissue, early life exposure, and the role of circadian rhythms. Risk factors such as sex and exposure to pollutants are also explored followed by a discussion of ways in which bioengineering approaches can be employed to help understand COVID-19. The use of sophisticated in vitro models can be employed to interrogate intercellular interactions and also to tease apart effects of the virus itself from the resulting immune response. Additionally, spatiotemporal information can be gleaned from these models to learn more about the dynamics of the virus and COVID-19 progression. Application of advanced tissue and organ system models into COVID-19 research can result in more nuanced insight into the mechanisms underlying this condition and elucidate strategies to combat its effects.
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Affiliation(s)
- Jasmine Shirazi
- Department of Biomedical Engineering, University of Delaware, 161 Colburn Lab, Newark, DE 19716 USA
| | - Michael J. Donzanti
- Department of Biomedical Engineering, University of Delaware, 161 Colburn Lab, Newark, DE 19716 USA
| | - Katherine M. Nelson
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716 USA
| | - Ryan Zurakowski
- Department of Biomedical Engineering, University of Delaware, 161 Colburn Lab, Newark, DE 19716 USA
| | - Catherine A. Fromen
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716 USA
| | - Jason P. Gleghorn
- Department of Biomedical Engineering, University of Delaware, 161 Colburn Lab, Newark, DE 19716 USA
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Barone MTU, Ngongo B, Menna-Barreto L. Sleep-wake cycle impairment adding on the risk for COVID-19 severity in people with diabetes. Sleep Sci 2020; 13:191-194. [PMID: 33381286 PMCID: PMC7755262 DOI: 10.5935/1984-0063.20200038] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 07/14/2020] [Indexed: 01/16/2023] Open
Abstract
In the present article, we explore the risks of circadian disruptions and impact on the sleep-wake cycle of individuals with diabetes during COVID-19 pandemic. The association between the duration and quality of sleep and the stability of glucose levels is well-established. Therefore, during the pandemic with changes and limitations in the exposure to cyclic cues that entrain the circadian rhythms, such as light-dark and social interactions, we hypothesize that the power and stability of circadian rhythms decrease if measures are not taken to intentionally create a routine that includes zeitgebers. Knowing that sleep-wake cycle disruptions impair melatonin production, immune system response and glucose metabolism, and that individuals with diabetes are at higher risk for poor prognosis when infected by SARS-CoV-2 (especially if their blood glucose is out of target), we recommend monitoring and advising these individuals towards strategies to maintain adequate sleep quality and duration as part of their preventive and protective measures during the new pandemic routine.
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Affiliation(s)
- Mark Thomaz Ugliara Barone
- International Diabetes Federation (IDF), Board of Directors - Brussels - Brussels - Belgium
- ADJ Diabetes Brasil, Research and Education - Sao Paulo - SP - Brazil
- Fórum Intersetorial para Combate às DCNTs no Brasil (FórumDCNTs), General Management - Sao Paulo - SP - Brazil
- Sociedade Brasileira de Diabetes (SBD), Education - Sao Paulo - SP - Brazil
| | - Belinda Ngongo
- Pan African Women in Health (PAWH), Founder - Johannesburg - Gauteng - South Africa
| | - Luiz Menna-Barreto
- Escola de Artes, Ciências e Humanidades - Universidade de Sao Paulo (EACH-USP), Grupo Multidisciplinar de Desenvolvimento e Ritmos Biológicos (GMDRB) - Sao Paulo - SP - Brazil
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Meira E Cruz M, Miyazawa M, Gozal D. Putative contributions of circadian clock and sleep in the context of SARS-CoV-2 infection. Eur Respir J 2020; 55:2001023. [PMID: 32350105 PMCID: PMC7191115 DOI: 10.1183/13993003.01023-2020] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Accepted: 04/20/2020] [Indexed: 12/20/2022]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the aetiological agent of the pandemic coronavirus disease 2019 (COVID-19), is a newly found member of the Coronaviridae family, and is closely related to, albeit with important differences from, SARS-CoV [1]. It enters human cells through the binding of surface spike (S) glycoprotein with angiotensin-converting enzyme 2 (ACE2) [2–4]. The distal S1 subunit of the S protein is responsible for receptor binding, while the transmembrane S2 subunit mediates fusion between the viral envelope and the target cell membrane following proteolytic cleavage by specific cellular enzymes such as transmembrane serine protease 2 for S protein priming [5]. As it is likely that expression levels of ACE2 affect the efficiency of virus attachment and entry, as well as disease severity [6], and the interactions between viral S protein and ACE2 may directly cause lung injury [7], ACE2 may be a potential target of therapeutic and preventative interventions [8]. Circadian deregulation and poor or insufficient sleep may facilitate COVID-19 infection and severity https://bit.ly/2VUlIIJ
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Affiliation(s)
- Miguel Meira E Cruz
- Sleep Unit, Cardiovascular Center of University of Lisbon, Lisbon School of Medicine, Lisbon, Portugal
- Equal contributors
| | - Masaaki Miyazawa
- Dept of Immunology, Faculty of Medicine and Anti-Aging Center, Kindai University, Osaka, Japan
- Equal contributors
| | - David Gozal
- Dept of Child Health and the Child Health Research Institute, The University of Missouri School of Medicine, Columbia, MO, USA
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