Maternal circadian rhythm disruption affects neonatal inflammation via metabolic reprograming of myeloid cells.

Disruption of circadian rhythm during pregnancy produces adverse health outcomes in offspring; however, the role of maternal circadian rhythms in the immune system of infants and their susceptibility to inflammation remains poorly understood. Here we show that disruption of circadian rhythms in pregnant mice profoundly aggravates the severity of neonatal inflammatory disorders in both male and female offspring, such as necrotizing enterocolitis and sepsis. The diminished maternal production of docosahexaenoic acid (DHA) and the impaired immunosuppressive function of neonatal myeloid-derived suppressor cells (MDSCs) contribute to this phenomenon. Mechanistically, DHA enhances the immunosuppressive function of MDSCs via PPARγ-mediated mitochondrial oxidative phosphorylation. Transfer of MDSCs or perinatal supplementation of DHA relieves neonatal inflammation induced by maternal rhythm disruption. These observations collectively demonstrate a previously unrecognized role of maternal circadian rhythms in the control of neonatal inflammation via metabolic reprograming of myeloid cells.

GOSpel for tiny allies.

Infant formulas are often supplemented to foster the development of a healthy gut microbiota. In this issue of Cell Host & Microbe, Heppner et al. present an elaborate clinical trial examining the impact of formula supplementation on the development and circadian rhythmicity of the microbiota during the first year of life.

Serial Home Blood Pressure and Heart Rate Measurements for Optimized Management.

BACKGROUND: Serial blood pressure and heart rate measurements, particularly obtained by the patients at home, are currently recommended for the management of patients. METHODS: Home blood pressure and heart rate measurements were obtained by an 81-year old husband and his 74-year old wife in the morning and evening, over the course of an entire month. RESULTS: Morning and evening systolic blood pressure (129.9 ± 5.5, 125.9 ± 10.2, respectively), and diastolic blood pressure (69.2 ± 4.0, 70.1 ± 5.3) were not different (P > .05), heart rate (61.2 ± 2.9, 69.0 ± 5.5) was higher in the evening (P = .00001) in the husband, while systolic blood pressure (134.7 ± 9.6, 119.0 ± 12.0) and diastolic blood pressure (78.6 ± 5.6, 72.1 ± 7.3) were higher in the morning (P = .00001, P = .00031), and heart rate (62.7 ± 4.7, 68.2 ± 4.6) was higher in the evening (P = .00017) in the wife. CONCLUSIONS: Patient-generated serial home blood pressure and heart rate logs provide essential data for the patients' management and could potentially be useful in research; circadian variation of blood pressure and heart rate calls for implementation of chronotherapeutic principles for the time of drug administration.

The impact of sleep education, light intervention and relaxation on sleep and mood in the elderly.

Sleep and light education (SLE) combined with relaxation is a potential method of addressing sleep and affective problems in older people. 47 participants took part in a four-week sleep education program. SLE was conducted once a week for 60-90 minutes. Participants were instructed on sleep and light hygiene, sleep processes, and practiced relaxation techniques. Participants were wearing actigraphs for 6 weeks, completed daily sleep diaries, and wore blue light-blocking glasses 120 minutes before bedtime. Measures included scores of the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISS), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI) and actigraphy measurements of sleep latency, sleep efficiency, and sleep fragmentation. Sleep quality increased after SLE based on the subjective assessment and in the objective measurement with actigraphy. PSQI scores were statistically reduced indicating better sleep. Scores after the intervention significantly decreased in ESS and ISS. Sleep latency significantly decreased, whereas sleep efficiency and fragmentation index (%), did not improve. Mood significantly improved after SLE, with lower scores on the BDI-II and STAI. SLE combined with relaxation proved to be an effective method to reduce sleep problems and the incidence of depressive and anxiety symptoms.

Circadian rhythm response and its effect on photosynthetic characteristics of the Lhcb family genes in tea plant.

BACKGROUND: The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. RESULTS: In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. CONCLUSIONS: Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.

Impact of chrono-radiotherapy on the prognosis and treatment-related toxicity in patients with locally advanced nasopharyngeal carcinoma: A multicenter propensity-matched study.

The timing of radiotherapy (RT) delivery has been reported to affect both cancer survival and treatment toxicity. However, the association among the timing of RT delivery, survival, and toxicity in locally advanced nasopharyngeal carcinoma (LA-NPC) has not been investigated. We retrospectively reviewed patients diagnosed with LA-NPC who received definitive RT at multiple institutions. The median RT delivery daytime was categorized as morning (DAY) and night (NIGHT). Seasonal variations were classified into the darker half of the year (WINTER) and brighter half (SUMMER) according to the sunshine duration. Cohorts were balanced according to baseline characteristics using propensity score matching (PSM). Survival and toxicity outcomes were evaluated using Cox regression models. A total of 355 patients were included, with 194/161 in DAY/NIGHT and 187/168 in WINTER/SUMMER groups. RT delivered during the daytime prolonged the 5-year overall survival (OS) (90.6% vs. 80.0%, p = 0.009). However, the significance of the trend was lost after PSM (p = 0.068). After PSM analysis, the DAY cohort derived a greater benefit in 5-year progression-free survival (PFS) (85.6% vs. 73.4%, p = 0.021) and distant metastasis-free survival (DMFS) (89.2% vs. 80.8%, p = 0.051) in comparison with the NIGHT subgroup. Moreover, multivariate analysis showed that daytime RT was an independent prognostic factor for OS, PFS, and DMFS. Furthermore, daytime RT delivery was associated with an increase in the incidence of leukopenia and radiation dermatitis. RT delivery in SUMMER influenced only the OS significantly (before PSM: p = 0.051; after PSM: p = 0.034). There was no association between toxicity and the timing of RT delivery by season. In LA-NPC, the daytime of radical RT served as an independent prognostic factor. Furthermore, RT administered in the morning resulted in more severe toxic side effects than that at night, which needs to be confirmed in a future study.

Circadian rhythm mechanism in the suprachiasmatic nucleus and its relation to the olfactory system.

Animals need sleep, and the suprachiasmatic nucleus, the center of the circadian rhythm, plays an important role in determining the timing of sleep. The main input to the suprachiasmatic nucleus is the retinohypothalamic tract, with additional inputs from the intergeniculate leaflet pathway, the serotonergic afferent from the raphe, and other hypothalamic regions. Within the suprachiasmatic nucleus, two of the major subtypes are vasoactive intestinal polypeptide (VIP)-positive neurons and arginine-vasopressin (AVP)-positive neurons. VIP neurons are important for light entrainment and synchronization of suprachiasmatic nucleus neurons, whereas AVP neurons are important for circadian period determination. Output targets of the suprachiasmatic nucleus include the hypothalamus (subparaventricular zone, paraventricular hypothalamic nucleus, preoptic area, and medial hypothalamus), the thalamus (paraventricular thalamic nuclei), and lateral septum. The suprachiasmatic nucleus also sends information through several brain regions to the pineal gland. The olfactory bulb is thought to be able to generate a circadian rhythm without the suprachiasmatic nucleus. Some reports indicate that circadian rhythms of the olfactory bulb and olfactory cortex exist in the absence of the suprachiasmatic nucleus, but another report claims the influence of the suprachiasmatic nucleus. The regulation of circadian rhythms by sensory inputs other than light stimuli, including olfaction, has not been well studied and further progress is expected.

Pioneering new frontiers in circadian medicine chronotherapies for cardiovascular health.

Cardiovascular disease (CVD) is a global health concern. Circadian medicine improves cardiovascular care by aligning treatments with our body's daily rhythms and their underlying cellular circadian mechanisms. Time-based therapies, or chronotherapies, show special promise in clinical cardiology. They optimize treatment schedules for better outcomes with fewer side effects by recognizing the profound influence of rhythmic body cycles. In this review, we focus on three chronotherapy areas (medication, light, and meal timing) with potential to enhance cardiovascular care. We also highlight pioneering research in the new field of rest, the gut microbiome, novel chronotherapies for hypertension, pain management, and small molecules that targeting the circadian mechanism.

Effect of exercise based interventions on sleep and circadian rhythm in cancer survivors-a systematic review and meta-analysis.

Background: Disrupted circadian rhythm commonly reported in cancer survivors is closely associated with cancer related fatigue, sleep disturbances and compromised quality of life. As more cancer survivors request non-pharmacological treatment strategies for the management of their chronic sleep-related symptoms, there is a need for meta-analyses of various interventions such as exercise on sleep and circadian rhythm disturbances. Methods: A search for RCT's was conducted in April 2020 and updated in July 2023 using relevant keywords for cancer, sleep, circadian rhythm and exercise interventions on PubMed, Scopus, Web of Science, PEDro and CINAHL. Results: Thirty-six studies were included for qualitative analysis and 26, for meta-analysis. Thirty-five studies analyzed sleep outcomes, while five analyzed circadian rhythm. RCT's studying the effect of aerobic exercise, resistance exercise, combined aerobic and resistance exercise, physical activity, yoga, or tai chi were included. Meta-analysis results showed significant exercise-related improvements on sleep quality assessed by Pittsburgh Sleep Quality index (PSQI) (SMD = -0.50 [-0.87, -0.13], p = 0.008), wake after sleep onset (WASO) (SMD = -0.29 [-0.53, -0.05], p = 0.02) and circadian rhythm, assessed by salivary cortisol levels (MD = -0.09 (95% CI [-0.13 to -0.06]) mg/dL, p < 0.001). Results of the meta-analysis indicated that exercise had no significant effect on sleep efficiency, sleep onset latency, total sleep time and circadian rhythm assessed by accelerometry values. Conclusion: While some sleep and circadian rhythm outcomes (PSQI, WASO and salivary cortisol) exhibited significant improvements, it is still somewhat unclear what exercise prescriptions would optimize different sleep and circadian rhythm outcomes across a variety of groups of cancer survivors. Implication: As exercise does not exacerbate cancer-related circadian rhythm and sleep disturbances, and may actually produce some significant benefits, this meta-analysis provides further evidence for cancer survivors to perform regular exercise.

Dissociating Mechanisms That Underlie Seasonal and Developmental Programs for the Neuroendocrine Control of Physiology in Birds.

Long-term programmed rheostatic changes in physiology are essential for animal fitness. Hypothalamic nuclei and the pituitary gland govern key developmental and seasonal transitions in reproduction. The aim of this study was to identify the molecular substrates that are common and unique to developmental and seasonal timing. Adult and juvenile quail were collected from reproductively mature and immature states, and key molecular targets were examined in the mediobasal hypothalamus (MBH) and pituitary gland. qRT-PCR assays established deiodinase type 2 (DIO2) and type 3 (DIO3) expression in adults changed with photoperiod manipulations. However, DIO2 and DIO3 remain constitutively expressed in juveniles. Pituitary gland transcriptome analyses established that 340 transcripts were differentially expressed across seasonal photoperiod programs and 1,189 transcripts displayed age-dependent variation in expression. Prolactin (PRL) and follicle-stimulating hormone subunit beta (FSHß) are molecular markers of seasonal programs and are significantly upregulated in long photoperiod conditions. Growth hormone expression was significantly upregulated in juvenile quail, regardless of photoperiodic condition. These findings indicate that a level of cell autonomy in the pituitary gland governs seasonal and developmental programs in physiology. Overall, this paper yields novel insights into the molecular mechanisms that govern developmental programs and adult brain plasticity.

Long-term effects of environmental dynamic lighting on sleep-wake rhythm, mood and behaviour in older adults with intellectual disabilities.

BACKGROUND: Sleep-wake problems and depressive symptoms are common in people with intellectual disabilities (IDs) and are thought to be related to the unstable sleep-wake rhythm in this population. Previously, we showed that after increasing environmental light exposure, mid-sleep and sleep onset advanced, and mood improved over a period of 14 weeks after installing environmental dynamic light installations in the living room of people with IDs. We invited participants of that short-term study to take part in the current study on sleep-wake rhythm, mood and behaviour in older adults with IDs 1 year after installing environmental dynamic light installations in the common living rooms of six group homes. METHODS: A pre-post study was performed from October 2017 to February 2019. We included 45 participants (63.5 ± 8.5 years, 67% female) from six group home facilities who provided data at baseline (9, 4 and 1 weeks prior to installing light installations), short term (3, 7 and 14 weeks after installing light installations) and 1 year (54 weeks after installing light installations). Wrist activity was measured with actigraphy (GENEActiv) to derive the primary outcome of interdaily stability of sleep-wake rhythms as well as sleep estimates. Mood was measured with the Anxiety, Depression and Mood Scale. Behaviour was measured with the Aberrant Behaviour Checklist. RESULTS: One year after installing dynamic lighting, we did not find a change in interdaily stability. Total sleep time decreased (ß = -25.40 min; confidence interval: -10.99, -39.82), and sleep onset time was delayed (ß = 25.63 min; confidence interval: 11.18, 40.08). No effect on mood or behaviour was found. CONCLUSIONS: We did not find a change in sleep-wake rhythm, mood or behaviour in older persons with IDs living in care facilities 1 year after installing the light. We did find evidence for a long-term effect on sleep duration and sleep timing. The results have to be interpreted with care as the current study had a limited number of participants. The need for more research on the long-term effects of enhancing environmental light in ID settings is evident.

Circadian rhythm of intraocular pressure.

Intraocular pressure (IOP) plays a crucial role in glaucoma development, involving the dynamics of aqueous humor (AH). AH flows in from the ciliary body and exits through the trabecular meshwork (TM). IOP follows a circadian rhythm synchronized with the suprachiasmatic nucleus (SCN), the circadian pacemaker. The SCN resets peripheral clocks through sympathetic nerves or adrenal glucocorticoids (GCs). IOP's circadian rhythm is governed by circadian time signals, sympathetic noradrenaline (NE), and GCs, rather than the local clock. The activity of Na+/K+-ATPase in non-pigmented epithelial cells in the ciliary body can influence the nocturnal increase in IOP by enhancing AH inflow. Conversely, NE, not GCs, can regulate the IOP rhythm by suppressing TM macrophage phagocytosis and AH outflow. The activation of the ß1-adrenergic receptor (AR)-mediated EPAC-SHIP1 signal through the ablation of phosphatidylinositol triphosphate may govern phagocytic cup formation. These findings could offer insights for better glaucoma management, such as chronotherapy.

[Insomnia and the biological clock]. / Insomnie et horloge biologique.

INSOMNIA AND THE BIOLOGICAL CLOCK. Multiple physiological and biological rhythms known as «circadian¼ are generated by the biological clock that controls them within the suprachiasmatic nuclei of the hypothalamus. However, the most emblematic circadian rhythm is that of sleep and awakening. It is therefore crucial to check how the clock may be involved in chronic insomnia. What is the influence of the clock on the time and quality of sleep? What are the typical clock disorders that explain insomnia in adolescents, shift and night workers, the elderly and the blind individuals? What are the tools to recommend in general and specialized medicine in the evaluation of the clock in insomnia? What influence finally of the light on the clock and the light therapy to recommend? So many questions and elements of understanding often-poorly known of chronic insomnia.

INSOMNIE ET HORLOGE BIOLOGIQUE. De multiples rythmes physiologiques et biologiques dits « circadiens ¼ sont influencés par l'horloge biologique qui les contrôle au sein des noyaux suprachiasmatiques de l'hypothalamus. Mais le rythme circadien le plus emblématique est celui du sommeil et de l'éveil. Il est donc indispensable de vérifier comment l'horloge biologique peut être impliquée dans une insomnie chronique : quelle est son influence sur les horaires et la qualité du sommeil ? Quels sont les troubles caractéristiques de l'horloge biologique expliquant l'insomnie des adolescents, des travailleurs postés et de nuit, des personnes âgées et des non-voyants ? Quels outils conseiller en médecine générale et spécialisée pour évaluer l'horloge biologique face à une insomnie ? Quelle influence, enfin, de la lumière sur l'horloge biologique et quels conseils donner vis-à-vis de la lumière ? Autant de questions et d'éléments de compréhension sur l'insomnie chronique éclaircis.

Circadian Influences on Myocardial Ischemia-Reperfusion Injury and Heart Failure.

The impact of circadian rhythms on cardiovascular function and disease development is well established, with numerous studies in genetically modified animals emphasizing the circadian molecular clock's significance in the pathogenesis and pathophysiology of myocardial ischemia and heart failure progression. However, translational preclinical studies targeting the heart's circadian biology are just now emerging and are leading to the development of a novel field of medicine termed circadian medicine. In this review, we explore circadian molecular mechanisms and novel therapies, including (1) intense light, (2) small molecules modulating the circadian mechanism, and (3) chronotherapies such as cardiovascular drugs and meal timings. These promise significant clinical translation in circadian medicine for cardiovascular disease. (4) Additionally, we address the differential functioning of the circadian mechanism in males versus females, emphasizing the consideration of biological sex, gender, and aging in circadian therapies for cardiovascular disease.

Stroke in the Time of Circadian Medicine.

Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also for important determinants of clinical outcome. In this review, we provide a comprehensive overview of the interplay between chronobiology and cerebrovascular disease. We discuss circadian regulation of pathophysiological mechanisms underlying stroke onset or tolerance as well as in vascular dementia. This includes cell death mechanisms, metabolism, mitochondrial function, and inflammation/immunity. Furthermore, we present clinical evidence supporting the link between disrupted circadian rhythms and increased susceptibility to stroke and dementia. We propose that circadian regulation of biochemical and physiological pathways in the brain increase susceptibility to damage after stroke in sleep and attenuate treatment effectiveness during the active phase. This review underscores the importance of considering circadian biology for understanding the pathology and treatment choice for stroke and vascular dementia and speculates that considering a patient's chronotype may be an important factor in developing precision treatment following stroke.

High dose cholecalciferol supplementation causing morning blood pressure reduction in patients with type 1 diabetes mellitus and cardiovascular autonomic neuropathy.

We evaluated the association of cardiovascular autonomic neuropathy (CAN), blood pressure (BP) and Vitamin D (VD) levels before and after high-dose cholecalciferol supplementation (4000/10,000) UI/day) for 12 weeks in patients (N = 67) with type 1 diabetes mellitus (T1DM). Based on this prospective controlled pilot study, patients were divided into group 1 (N = 23 with CAN) and group 2 (N = 44 without CAN). At baseline, group 1 had higher systolic BP (SBP) during sleep (115 ± 14 vs. 107 ± 12 mmHg, p = 0.04) and lower nocturnal dipping (3 ± 5 vs. 8 ± 6%, p = 0.009). Among those with loss of nocturnal dipping, 45.4% (20/44) had CAN, while in normal nocturnal dipping group it occurred only in 13% (3/23) (p = 0.007). Non-dipper group had worse CAN parameters when compared to dipper group [Very low frequency (VLF) (2.5 ± 0.5vs.2.8 ± 0.4 s, p = 0.01), total power (TP) (2.9 ± 0.6 vs. 3.3 ± 0.4 s, p = 0.01), Valsalva coefficient (1.5 ± 0.4 vs. 1.8 ± 0.6, p = 0.06)]. After VD, only group 1 improved CAN parameters [TP (2.5 ± 0.4 vs. 2.8 ± 0.6, p = 0.01) and VLF (2.2 ± 0.4 vs. 2.4 ± 0.5, p = 0.03). Group 1 presented a reduction in morning SBP (120 ± 20 vs. 114 ± 17 mmHg, p = 0.038) and in morning SBP surge (13 ± 13 vs. 5 ± 14, p = 0.04). High-dose VD was associated with improved CAN parameters and reduced awake SBP and morning SBP surge. These findings suggest that VD may benefit patients with cardiovascular autonomic neuropathy. ISRCTN32601947, registration date: 31/07/2017.

Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery.

The blood-brain barrier (BBB) is a critical interface separating the central nervous system from the peripheral circulation, ensuring brain homeostasis and function. Recent research has unveiled a profound connection between the BBB and circadian rhythms, the endogenous oscillations synchronizing biological processes with the 24-hour light-dark cycle. This review explores the significance of circadian rhythms in the context of BBB functions, with an emphasis on substrate passage through the BBB. Our discussion includes efflux transporters and the molecular timing mechanisms that regulate their activities. A significant focus of this review is the potential implications of chronotherapy, leveraging our knowledge of circadian rhythms for improving drug delivery to the brain. Understanding the temporal changes in BBB can lead to optimized timing of drug administration, to enhance therapeutic efficacy for neurological disorders while reducing side effects. By elucidating the interplay between circadian rhythms and drug transport across the BBB, this review offers insights into innovative therapeutic interventions.

Chrononutrition in traditional European medicine-Ideal meal timing for cardiometabolic health promotion.

Meal timing plays a crucial role for cardiometabolic health, given the circadian regulation of cardiometabolic function. However, to the best of our knowledge, no concept of meal timing exists in traditional European medicine (TEM). Therefore, in this narrative review, we aim to define the optimal time slot for energy intake and optimal energy distribution throughout the day in a context of TEM and explore further implications. By reviewing literature published between 2002 and 2022, we found that optimal timing for energy intake may be between 06:00 and 09:00, 12:00 and 14:00, and between 15:00 and 18:00, with high energy breakfast, medium energy lunch and low energy dinner and possibly further adjustments according to one's chronotype and genetics. Also, timing and distribution of energy intake may serve as a novel therapeutic strategy to optimize coction, a concept describing digestion and metabolism in TEM. Please cite this article as: Eberli NS, Colas L, Gimalac A. Chrononutrition in traditional European medicine-Ideal meal timing for cardiometabolic health promotion. J Integr Med. 2024; 22(2);115-125.

Quercetin improved hepatic circadian rhythm dysfunction in middle-aged mice fed with vitamin D-deficient diet

We aimed to determine whether quercetin is capable of improving circadian rhythm and metabolism disorder under vitamin D-deficient condition. Middle-aged mice were randomly divided into four groups, namely, control (CON), vitamin D-deficient diet (VDD), quercetin (Q), and quercetin intervention in vitamin D-deficient diet (VDQ), with a total of 12 weeks’ intervention. Mice were sacrificed at zeitgeber time1 (ZT1) and ZT13 time points. At ZT1, circadian locomotor output cycle kaput (CLOCK) protein expression from VDD, Q, and VDQ groups; CRY1 from Q group; and CRY2 from VDD group were significantly lower compared to CON group. The mRNA expression of Sirt1, Bmal1, Clock, Cry1, and Cry2 in VDQ groups, also Bmal1, Clock, and Cry1 from Q group, were significantly decreased compared to CON group. At ZT13, compared to CON group, fasting insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were higher in VDD group; BMAL1 was significantly increased, while CLOCK and CRY1 protein were significantly decreased from VDD group; CLOCK protein from VDQ group was significantly higher compared to CON, VDD, and Q groups, and also, BMAL1 protein expression from VDQ group was elevated compared to CON group. The mRNA expression of Bmal1, Clock, Per2, Cry1, and Cry2 in VDQ groups were significantly increased compared to CON groups. The mRNA expression of Bmal1 from VDQ group was decreased compared to both VDD and Q group. In conclusion, vitamin D-deficient diet resulted in a disordered liver circadian rhythm, and quercetin improved the hepatic circadian desynchronization. Quercetin supplementation might be effective for balancing circadian rhythm under vitamin D-deficient condition. (AU)