Circadian rhythm disruption in critically ill patients

Acta Physiologica, Год журнала: 2023, Номер 238(1)

Опубликована: Март 14, 2023

Abstract Patients admitted to the intensive care unit (ICU) are in need of continuous organ replacement strategies and specialized care, for example because neurological dysfunction, cardio‐pulmonary instability, liver or kidney failure, trauma, hemorrhagic septic shock even preterm birth. The 24‐h nursing interventions provided critically ill patients significantly limit resting and/or recovery phases. Consecutively, patient's endogenous circadian rhythms misaligned disrupted, which turn may interfere with their critical condition. A more thorough understanding complex interactions effectors tissue‐specific molecular clocks could therefore serve as potential means enhancing personalized treatment patients, conceivably restoring network thus accelerating physical neurocognitive recovery. This review addresses overarching issue how affected disturbed newborns adults ICU, whether conflicting external environmental cues ICU environment further promote disruption severity illness. We direct special attention influence cell‐type specific on dysfunctions such brain pneumonia‐ ventilator‐associated lung inflammation, cardiovascular shock. Finally, we address rhythm stabilization enhance accelerate clinical

Язык: Английский

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Circadian clock molecule REV-ERBα regulates lung fibrotic progression through collagen stabilization

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Март 9, 2023

Abstract Molecular clock REV-ERBα is central to regulating lung injuries, and decreased abundance mediates sensitivity pro-fibrotic insults exacerbates fibrotic progression. In this study, we determine the role of in fibrogenesis induced by bleomycin Influenza A virus (IAV). Bleomycin exposure decreases REV-ERBα, mice dosed with at night display exacerbated fibrogenesis. Rev-erbα agonist (SR9009) treatment prevents collagen overexpression mice. global heterozygous (Rev-erbα Het) infected IAV showed augmented levels collagens lysyl oxidases compared WT-infected Furthermore, (GSK4112) oxidase TGFβ human fibroblasts, whereas antagonist it. Overall, these results indicate that loss responses promoting expression, This study provides potential agonists pulmonary fibrosis.

Язык: Английский

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Association of rest-activity circadian rhythm with chronic respiratory diseases, a cross-section survey from NHANES 2011–2014

Respiratory Medicine, Год журнала: 2023, Номер 209, С. 107147 - 107147

Опубликована: Фев. 6, 2023

Язык: Английский

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Resetting of the Human Circadian Melatonin Rhythm by Ambient Hypoxia

Journal of Pineal Research, Год журнала: 2025, Номер 77(1)

Опубликована: Янв. 1, 2025

ABSTRACT Circadian clocks in the body drive daily cycles physiology and behavior. A master clock brain maintains synchrony with environmental day–night cycle uses internal signals to keep other tissues aligned. Work cell cultures uncovered cyclic changes tissue oxygenation that may serve reset synchronize circadian clocks. Here we show healthy humans, following a randomized controlled single‐blind counterbalanced crossover study design, one‐time exposure moderate ambient hypoxia (FiO 2 ~15%, normobaric) for ~6.5 h during early night advances dim‐light onset of melatonin secretion by 9 min (95% CI: 1–16 min). Exposure thus be strong enough entrain 24‐h absence entraining cues. Together, results provide direct evidence an interaction between body's hypoxia‐sensing pathway The finding offers mechanism through which behaviors change (e.g., exercise fasting/eating) can affect timing hypoxia‐related diseases obstructive sleep apnea chronic pulmonary disease) result misalignment associated pathologies. Trial Registration: Registration number: DRKS00023387; German Clinical Trials Register: http://www.drks.de

Язык: Английский

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The circadian clock at the intersection of metabolism and aging – emerging roles of metabolites

Journal of genetics and genomics/Journal of Genetics and Genomics, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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The circadian clock and extracellular matrix homeostasis in aging and age-related diseases

AJP Cell Physiology, Год журнала: 2023, Номер 325(1), С. C52 - C59

Опубликована: Май 29, 2023

The extracellular matrix (ECM) is the noncellular scaffolding component present within all tissues and organs. It provides crucial biochemical biomechanical cues to instruct cellular behavior has been shown be under circadian clock regulation, a highly conserved cell-intrinsic timekeeping mechanism that evolved with 24-hour rhythmic environment. Aging major risk factor for many diseases, including cancer, fibrosis, neurodegenerative disorders. Both aging our modern 24/7 society disrupt rhythms, which could contribute altered ECM homeostasis. Understanding daily dynamics of how this changes age will have profound impact on tissue health, disease prevention, improving treatments. Maintaining oscillations proposed as hallmark health. On other hand, hallmarks turn out key regulators mechanisms. In review, we summarize new work linking clocks aging. We discuss in properties during may dysregulation. also consider dampening compromise dynamic regulation homeostasis matrix-rich tissues. This review aims encourage concepts testable hypotheses about two-way interactions between context

Язык: Английский

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Associations between long-term night shift work and incidence of chronic obstructive pulmonary disease: a prospective cohort study of 277,059 UK Biobank participants

BMC Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 16, 2024

Abstract Background Little is known about the effects of night shifts and their interactions with genetic factors on chronic obstructive pulmonary disease (COPD). In this study, we aim to investigate relationships between long-term shift work exposure COPD risk, assess modification predisposition. Methods A total 277,059 subjects who were in paid employment or self-employed included UK Biobank. Information current lifetime was obtained, a weighted COPD-specific risk score (GRS) constructed. We used Cox proportional hazard models associations interaction GRS. Results The cohort study participants (133,063 men [48.03%]; mean [SD] age, 52.71 [7.08] years). During median follow-up 12.87 years, documented 6558 incidents COPD. From day work, irregular regular shifts, there an increased trend incidence ( P for < 0.001). Compared workers, ratio (HR) 95% confidence interval (CI) 1.28 (1.20, 1.37) rarely/sometimes 1.49 (1.35, 1.66) those permanent shifts. Besides, longer durations (especially ≥ 10 years) increasing monthly frequency (in workers > 8 nights/month) associated higher risk. Additionally, additive susceptibility Subjects high had highest (HR: 1.90 [95% CI: 1.63, 2.22]), low as reference. Conclusions Long-term Our findings suggest that decreasing duration may offer promising approach mitigating respiratory particularly light individual susceptibility.

Язык: Английский

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YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS

Cell Reports, Год журнала: 2024, Номер 43(3), С. 113947 - 113947

Опубликована: Март 1, 2024

N6-methyladenosine (m6A) modification has been implicated in many cell processes and diseases. YTHDF1, a translation-facilitating m6A reader, not previously shown to be related allergic airway inflammation. Here, we report that YTHDF1 is highly expressed epithelial cells asthmatic patients it influences proinflammatory responses. CLOCK, subunit of the circadian clock pathway, direct target YTHDF1. augments CLOCK translation an m6A-dependent manner. Allergens enhance liquid-liquid phase separation (LLPS) drive formation complex comprising dimeric mRNA, which distributed stress granules. Moreover, strongly activates NLRP3 inflammasome production interleukin-1β secretion leading inflammatory responses, but these phenotypes are abolished by deleting CLOCK. These findings demonstrate important regulator inflammation, suggesting potential therapeutic for

Язык: Английский

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Complement Immune System in Pulmonary Hypertension-Cooperating Roles of Circadian Rhythmicity in Complement-Mediated Vascular Pathology

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12823 - 12823

Опубликована: Ноя. 28, 2024

Originally discovered in the 1890s, complement system has traditionally been viewed as a "compliment" to body's innate and adaptive immune response. However, emerging data have shown that is much more complex mechanism within body involved regulating inflammation, gene transcription, attraction of macrophages, many processes. Sustained activation contributes autoimmunity chronic inflammation. Pulmonary hypertension disease with poor prognosis an average life expectancy 2-3 years leads vascular remodeling pulmonary arteries; arteries are essential host homeostasis, they divert deoxygenated blood from right ventricle heart lungs for gas exchange. This review focuses on direct links between system's involvement hypertension, along autoimmune conditions, reliance processes artery. Furthermore, circadian rhythmicity highlighted disrupted homeostatic inflammatory consequences arteries, which could potentially open new therapeutic cues. The current treatment options discussed clinical trials using inhibitors potential targets impact cell functions activation, alleviate symptoms block progression disease. Further research complement's interstitial lung diseases prove beneficial our understanding these various prevent arteries.

Язык: Английский

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Association of circadian syndrome and lung health: A population-based cohort study

Respiratory Medicine, Год журнала: 2025, Номер 240, С. 108031 - 108031

Опубликована: Март 9, 2025

Язык: Английский

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