"Circadian rhythm and toxic response, investigating consequences for experimental design for tox study using Cyclo phosphamide as case study"
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
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PROVIDER: S-DIXA-046 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description: Not available
| S-DIXA-047 | biostudies-other
Project description:Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important.
| S-EPMC5142605 | biostudies-literature
Project description:The Human T-cell lymphotropic virus type 1 (HTLV-1), an oncogenic virus belonging to the Deltaretrovirus genus, expresses various proteins, including Tax and HBZ, which can affect many cellular pathways. In this study, we have investigated the role of the circadian rhythm signaling pathway, a key regulator of human health, in the pathogenesis of HTLV-1 using Boolean Network analysis and laboratory methods. After an extensive search of the circadian rhythm pathway, we analyzed the relationships between the genes of this pathway using the R programming language and the BoolNet package. Subsequently, we examined the impact of viral proteins on the cellular clock rhythm genes. Finally, we identified three genes, PER2, CRY1, and DEC1, as the main checkpoints from the attractors obtained. These three genes and two viral genes, Tax and HBZ, were quantitatively assessed on two groups of individuals, including ten asymptomatic carriers infected with HTLV-1 and ten healthy individuals using the qRT-PCR method. Our results showed that the expression level of PER2 and DEC1 genes was significantly higher in the asymptomatic carriers compared to the healthy control group. Also, we recorded positive correlations between PER2 and DEC1, CRY1 and DEC1, and negative correlations between HBZ and CRY1 and DEC1. In this study, we suggested that in asymptomatic carriers, the virus might try to induce a chronic infection by escaping from the immune system due to an alteration in circadian rhythm pathways. We also detected three promising genes in this pathway that could have therapeutic or diagnostic value in these individuals. However, this possibility requires further research in different periods, different groups (e.g., ATLL and HAM/TSP), and examining a more significant number of circadian rhythm genes.
| S-EPMC11872412 | biostudies-literature
Project description:BackgroundMyocardial infarction (MI) is a medical emergency resulting from coronary artery occlusion. Patients with acute MI often experience disturbed sleep and circadian rhythm. Most previous studies assessed the premorbid sleep and circadian rhythm of patients with MI and their correlations with cardiovascular disease. However, little is known about post-MI sleep and circadian rhythm and their impacts on prognosis. The use of actigraphy with different algorithms to evaluate sleep and circadian rhythm after acute MI has the potential for predicting outcomes and preventing future disease progression.ObjectiveWe aimed to evaluate how sleep patterns and disrupted circadian rhythm affect the prognosis of MI, using actigraphy and heart rate variability (HRV). Nonparametric analysis of actigraphy data was performed to examine the circadian rhythm of patients.MethodsPatients with MI in the intensive care unit (ICU) were enrolled alongside age- and gender-matched healthy controls. Actigraphy was used to evaluate sleep and circadian rhythm, while HRV was monitored for 24 hours to assess autonomic nerve function. Nonparametric indicators were calculated to quantify the active-rest patterns, including interdaily stability, intradaily variability, the most active 10 consecutive hours (M10), the least active 5 consecutive hours (L5), the relative amplitude, and the actigraphic dichotomy index. Follow-ups were conducted at 3 and 6 months after discharge to evaluate prognosis, including the duration of current admission, the number and duration of readmission and ICU admission, and catheterization. Independent sample t tests and analysis of covariance were used to compare group differences. Pearson correlation tests were used to explore the correlations of the parameters of actigraphy and HRV with prognosis.ResultsThe study included 34 patients with MI (mean age 57.65, SD 9.03 years) and 17 age- and gender-matched controls. MI patients had significantly more wake after sleep onset, an increased number of awakenings, and a lower sleep efficiency than controls. Circadian rhythm analysis revealed significantly lower daytime activity in MI patients. Moreover, these patients had a lower relative amplitude and dichotomy index and a higher intradaily variability and midpoint of M10, suggesting less sleep and wake activity changes, more fragmentation of the rest-activity patterns, and a more delayed circadian rhythm. Furthermore, significant correlations were found between the parameters of circadian rhythm analysis, including nighttime activity, time of M10 and L5, and daytime and nighttime activitySD, and patient prognosis.ConclusionsPatients with acute MI experienced significantly worse sleep and disturbed circadian rhythm compared with healthy controls. Our actigraphy-based analysis revealed a disturbed circadian rhythm, including reduced daytime activities, greater fluctuation in hourly activities, and a weak rest-activity rhythm, which were correlated with prognosis. The evaluation of sleep and circadian rhythm in patients with acute MI can serve as a valuable indicator for prognosis and should be further studied.
| S-EPMC11836589 | biostudies-literature
Project description:<p>The circadian rhythm is a 24 h cycle that harmonises the activity of organs – including the skin – to a daily routine using neurological and hormonal signals. Limited research has been done to understand the effects of the circadian rhythm on the skin lipidome. We used reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) in a longitudinal study to investigate temporal changes to the skin lipidome over a 24 h cycle for eight healthy participants. All statistical analyses were performed with a group-mean and individual-mean data approach. Using cosinor analysis p-values, a total of 29 metabolites (0.67% of all detected metabolites) exhibited a statistically significant circadian rhythmicity across participants; however, individually, a range of 3.51–18.53% of metabolites were considered rhythmic. The use of FDR q-values and Lomb–Scargle analysis showed no circadian metabolites. Using PCA and PLS-DA, no significant clustering based on timepoints was observed across participants; however, half of individuals showed significant metabolite clustering at 07:30. Further, sebum-specific squalene and sapienic acid as well as stratum corneum-specific cholesterol sulfate showed no significant differences in concentrations across timepoints. While individuals exhibited temporal differences, as an averaged healthy cohort the impacts by the circadian rhythm or time of sampling were considered negligible.</p>
2025-10-17 | MTBLS12607 | MetaboLights
Project description:Gut Microbe-Targeted Choline Trimethylamine Lyase Inhibition Improves Obesity Via Rewiring of Host Circadian Rhythms.
| PRJEB48232 | ENA
Project description:Circadian rhythm is an important mechanism that controls behavior and biochemical events based on 24 h rhythmicity. Ample evidence indicates disturbance of this mechanism is associated with different diseases such as cancer, mood disorders, and familial delayed phase sleep disorder. Therefore, drug discovery studies have been initiated using high throughput screening. Recently the crystal structures of core clock proteins (CLOCK/BMAL1, Cryptochromes (CRY), Periods), responsible for generating circadian rhythm, have been solved. Availability of structures makes amenable core clock proteins to design molecules regulating their activity by using in silico approaches. In addition to that, the implementation of classification features of molecules based on their toxicity and activity will improve the accuracy of the drug discovery process. Here, we identified 171 molecules that target functional domains of a core clock protein, CRY1, using structure-based drug design methods. We experimentally determined that 115 molecules were nontoxic, and 21 molecules significantly lengthened the period of circadian rhythm in U2OS cells. We then performed a machine learning study to classify these molecules for identifying features that make them toxic and lengthen the circadian period. Decision tree classifiers (DTC) identified 13 molecular descriptors, which predict the toxicity of molecules with a mean accuracy of 79.53% using tenfold cross-validation. Gradient boosting classifiers (XGBC) identified 10 molecular descriptors that predict and increase in the circadian period length with a mean accuracy of 86.56% with tenfold cross-validation. Our results suggested that these features can be used in QSAR studies to design novel nontoxic molecules that exhibit period lengthening activity.
| S-EPMC8445970 | biostudies-literature
Project description:Alzheimer's disease (AD) is a neurodegenerative disorder with a growing epidemiological importance characterized by significant disease burden. Sleep-related pathological symptomatology often accompanies AD. The etiology and pathogenesis of disrupted circadian rhythm and AD share common factors, which also opens the perspective of viewing them as a mutually dependent process. This article focuses on the bi-directional relationship between these processes, discussing the pathophysiological links and clinical aspects. Common mechanisms linking both processes include neuroinflammation, neurodegeneration, and circadian rhythm desynchronization. Timely recognition of sleep-specific symptoms as components of AD could lead to an earlier and correct diagnosis with an opportunity of offering treatments at an earlier stage. Likewise, proper sleep hygiene and related treatments ought to be one of the priorities in the management of the patient population affected by AD. This narrative review brings a comprehensive approach to clearly demonstrate the underlying complexities linking AD and circadian rhythm disruption. Most clinical data are based on interventions including melatonin, but larger-scale research is still scarce. Following a pathophysiological reasoning backed by evidence gained from AD models, novel anti-inflammatory treatments and those targeting metabolic alterations in AD might prove useful for normalizing a disrupted circadian rhythm. By restoring it, benefits would be conferred for immunological, metabolic, and behavioral function in an affected individual. On the other hand, a balanced circadian rhythm should provide greater resilience to AD pathogenesis.
| S-EPMC6164904 | biostudies-other
Project description:The olfactory neural circuitry plays a crucial role in regulating circadian rhythms. Our data demonstrate that mutation of the olfactory receptor orco in Drosophila significantly reduces rhythmicity in aged flies. Through neuPrint+ analysis and RNA-seq, we revealed that SIFamide (SIFa) neurons—which are associated with locomotor regulation—are closely connected to the olfactory neural circuit, and that the expression of the SIFa neuropeptide receptor (SiFaR) is significantly downregulated in orco mutants. Genetic evidence further indicates that olfactory receptor neurons receive external environmental signals and relay this information to SIFa neurons, thereby modulating the expression pattern of the core clock gene Period (Per), which ultimately affects circadian behavior in aging flies. Notably, the lifespan extension observed in orco mutants is closely associated with reduced Per expression in the gut. In summary, this study reveals that orco-dependent expression of Per in both the brain and the gut collectively contributes to age-related changes in circadian rhythmic behavior. This research provides new insights and a theoretical foundation for studying the mechanisms of aging by uncovering the intrinsic connection between olfactory neural circuits and circadian rhythmic behavior during aging.
2025-12-31 | GSE313711 | GEO
Project description: Not available
| ST001110 | MetabolomicsWorkbench