Search Results (245)

Background: Colorectal cancer (CRC) is strongly influenced by miRNAs as well as the circadian system. Methods: High-throughput sequencing of miRNAs expressed in the rat colon during 24 h light (L)/dark (D) cycle was performed to identify rhythmically expressed miRNAs. The role of miR-150-5p in CRC progression was analyzed in DLD1 cell line and human CRC tissues. Results: Nearly 10% of mature miRNAs showed a daily rhythm in expression. A peak of miRNAs’ levels was in most cases observed during the first half of the D phase of the LD cycle. The highest amplitude was detected in expression of miR-150-5p and miR-142-3p. In the L phase of the LD cycle, the maximum in miR-30d-5p expression was detected. Gene ontology enrichment analysis revealed that genes interfering with miRNAs with peak expression during the D phase influence apoptosis, angiogenesis, the immune system, and EGF and TGF-beta signaling. Rhythm in miR-150-5p, miR-142-3p, and miR-30d-5p expression was confirmed by real-time PCR. Oncogenes bcl2 and myb and clock gene cry1 were identified as miR-150-5p targets. miR-150-5p administration promoted camptothecin-induced apoptosis. Expression of myb showed a rhythmic profile in DLD1 cells with inverted acrophase with respect to miR-150-5p. miR-150-5p was decreased in cancer compared to adjacent tissue in CRC patients. Decrease in miR-150-5p was age dependent. Older patients with lower expression of miR-150-5p and higher expression of cry1 showed worse survival in comparison with younger patients. Conclusions: miRNA signaling differs between the L and D phases of the LD cycle. miR-150-5p, targeting myb, bcl2, and cry1, can influence CRC progression in a phase-dependent manner. Full article

Continuous blood pressure (BP) monitoring provides valuable insight into the body’s dynamic cardiovascular regulation across various physiological states such as physical activity, emotional stress, postural changes, and sleep. Continuous BP monitoring captures different variations in systolic and diastolic pressures, reflecting autonomic nervous system activity, vascular compliance, and circadian rhythms. This enables early identification of abnormal BP trends and allows for timely diagnosis and interventions to reduce the risk of cardiovascular diseases (CVDs) such as hypertension, stroke, heart failure, and chronic kidney disease as well as chronic stress or anxiety disorders. To facilitate continuous BP monitoring, we propose an AI-powered estimation framework. The proposed framework first uses an expert-driven feature engineering approach that systematically extracts physiological features from photoplethysmogram (PPG)-based arterial pulse waveforms (APWs). Extracted features include pulse rate, ascending/descending times, pulse width, slopes, intensity variations, and waveform areas. These features are fused with demographic data (age, gender, height, weight, BMI) to enhance model robustness and accuracy across diverse populations. The framework utilizes a Tab-Transformer to learn rich feature embeddings, which are then processed through an ensemble machine learning framework consisting of CatBoost, XGBoost, and LightGBM. Evaluated on a dataset of 1000 subjects, the model achieves Mean Absolute Errors (MAE) of 3.87 mmHg (SBP) and 2.50 mmHg (DBP), meeting British Hypertension Society (BHS) Grade A and Association for the Advancement of Medical Instrumentation (AAMI) standards. The proposed architecture advances non-invasive, AI-driven solutions for dynamic cardiovascular health monitoring. Full article

The circadian clock orchestrates behavioral and molecular processes such as eclosion. Understanding eclosion timing may offer insights into circadian mechanisms underlying migratory timing. Here, we characterize the diel and circadian patterns of eclosion and core clock gene expression in the fall armyworm (FAW), Spodoptera frugiperda, a globally distributed migratory moth. Using a custom-designed eclosion monitoring system under 14 h light: 10 h dark (L14: D10) and constant darkness (DD) conditions, we observed robust diel eclosion rhythms peaking shortly after lights-off under L14: D10, which became delayed and damped over three consecutive days in DD. Males showed a tendency toward more dispersed emergence patterns and exhibited statistically distinguishable eclosion distributions from females under both conditions. Expression of five canonical clock genes (cyc, clk, tim, per, cry2) displayed significant 24 h rhythmicity, with generally higher mesors in males. However, sex-specific differences in amplitude and phase were detected only for clk and cyc under L14: D10, not in DD. These findings suggest that sex-specific differences in circadian regulation are limited. Nonetheless, subtle variations in clock gene output and emergence timing in the FAW population established in China may contribute to sex-specific ecological strategies in the novel migratory arena. Full article

Developing early-heading wheat cultivars is an important breeding strategy to utilize light and heat resources, facilitate multiple-cropping systems, and enhance annual grain yield. Psathyrostachys huashanica Keng (2n = 2x = 14, NsNs) possesses numerous agronomically beneficial traits for wheat improvement, such as early maturity and resistance to biotic and abiotic stresses. In this study, we found that a cytogenetically stable wheat–P. huashanica 7Ns disomic addition line showed (9–11 days) earlier heading and (8–10 days) earlier maturation than its wheat parents. Morphological observations of spike differentiation revealed that the 7Ns disomic addition line developed distinctly faster than its wheat parents from the double ridge stage. To explore the potential molecular mechanisms underlying the early heading, we performed transcriptome analysis at four different developmental stages of the 7Ns disomic addition line and its wheat parents. A total of 10,043 differentially expressed genes (DEGs) were identified during spike development. Gene Ontology (GO) enrichment analysis showed that these DEGs were linked to the carbohydrate metabolic process, photosynthesis, response to abscisic acid, and the ethylene-activated signaling pathway. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these DEGs were involved in plant hormone signal transduction (ARF, AUX/IAA, SAUR, DELLA, BRI1, and ETR), starch and sucrose metabolism (SUS1 and TPP), photosynthetic antenna proteins (Lhc), and circadian rhythm (PRR37, FT, Hd3a, COL, and CDF) pathways. In addition, several DEGs annotated as transcription factors (TFs), such as bHLH, bZIP, MADS-box, MYB, NAC, SBP, WRKY, and NF-Y, may be related to flowering time. Our findings reveal spike development-specific gene expression and critical regulatory pathways associated with early heading in the wheat–P. huashanica 7Ns addition line, and provide a new genetic resource for further dissection of the molecular mechanisms underlying the heading date in wheat. Full article

Circadian rhythms govern cellular metabolism, redox balance, and endocrine signaling in numerous tissues. However, chronic disturbance of these biological rhythms, mediated by modern lifestyle factors including shift work, sleep irregularity, and prolonged light exposure, has been increasingly associated with oxidative stress, metabolic dysregulation, and the pathogenesis of chronic diseases. This review discusses recent mechanistic advances that link circadian misalignment with tissue-specific metabolic reprogramming and impaired proteostasis, focusing on metabolic inflammation and associated pathologies. Emerging work reveals a close interdependence between the circadian clock and proteasome-mediated protein turnover and highlights this interplay’s importance in maintaining redox homeostasis. Furthermore, circadian modulation of the activity of the inflammasome complex is suggested to represent an important, but largely unexplored, risk factor in the pathobiology of both malignancy and metabolic syndrome. Recently, researchers have proposed them as novel endocrine regulators of systemic energy balance and inflammation, with a focus on their circadian regulation. In addition, the emerging domains of chrono-epigenetics and tissue-specific programming of the clock pathways may serve to usher in novel therapies through precision medicine. Moving ahead, circadian-based therapeutic approaches, including time-restricted feeding, chronopharmacology, and metabolic rewiring, have high potential for re-establishing physiological domain homeostasis linked to metabolic inflammation pathologies. Elucidating this reciprocal relationship between circadian biology and cellular stress pathways may one day facilitate the generation of precise interventions aiming to alleviate the health burden associated with circadian disruption. Full article

Obesity and metabolic disorders remain major global health concerns, traditionally attributed to excessive caloric intake and poor diet quality. Recent studies emphasize that the timing of meals plays a crucial role in determining metabolic health. This review explores chrononutrition, a growing field that examines how food intake patterns interact with endogenous circadian rhythms to influence energy balance, glucose and lipid metabolism, and cardiometabolic risk. The circadian system, which includes a central clock in the suprachiasmatic nucleus and peripheral clocks in metabolic tissues, regulates physiological functions on a 24 h cycle. While light entrains the central clock, feeding schedules act as key synchronizers for peripheral clocks. Disrupting this alignment—common in modern lifestyles involving shift work or late-night eating—can impair hormonal rhythms, reduce insulin sensitivity, and promote adiposity. Evidence from clinical and preclinical studies suggests that early time-restricted eating, where food intake is confined to the morning or early afternoon, offers significant benefits for weight control, glycemic regulation, lipid profiles, and mitochondrial efficiency, even in the absence of caloric restriction. These effects are particularly relevant for populations vulnerable to circadian disruption, such as adolescents, older adults, and night-shift workers. In conclusion, aligning food intake with circadian biology represents a promising, low-cost, and modifiable strategy to improve metabolic outcomes. Integrating chrononutrition into clinical and public health strategies may enhance dietary adherence and treatment efficacy. Future large-scale studies are needed to define optimal eating windows, assess long-term sustainability, and establish population-specific chrononutritional guidelines. Full article

Chronobiotics represent a pharmacologically diverse group of substances, encompassing both experimental compounds and those utilized in clinical practice, which possess the capacity to modulate the parameters of circadian rhythms. These substances influence fluctuations in various physiological and biochemical processes, including the expression of core “clock” genes in model organisms and cell cultures, as well as the expression of clock-controlled genes. Despite their chemical heterogeneity, chronobiotics share the common ability to alter circadian dynamics. The concept of chronobiotic drugs has been recognized for over five decades, dating back to the discovery and detailed clinical characterization of the hormone melatonin. However, the field remains fragmented, lacking a unified classification system for these pharmacological agents. The current categorizations include natural chrononutrients, synthetic targeted circadian rhythm modulators, hypnotics, and chronobiotic hormones, yet no comprehensive repository of knowledge on chronobiotics exists. Addressing this gap, the development of the world’s first curated and continuously updated database of chronobiotic drugs—circadian rhythm modulators—accessible via the global Internet, represents a critical and timely objective for the fields of chronobiology, chronomedicine, and pharmacoinformatics/bioinformatics. The primary objective of this study is to construct a relational database, ChronobioticsDB, utilizing the Django framework and PostGreSQL as the database management system. The database will be accessible through a dedicated web interface and will be filled in with data on chronobiotics extracted and manually annotated from PubMed, Google Scholar, Scopus, and Web of Science articles. Each entry in the database will comprise a detailed compound card, featuring links to primary data sources, a molecular structure image, the compound’s chemical formula in machine-readable SMILES format, and its name according to IUPAC nomenclature. To enhance the depth and accuracy of the information, the database will be synchronized with external repositories such as ChemSpider, DrugBank, Chembl, ChEBI, Engage, UniProt, and PubChem. This integration will ensure the inclusion of up-to-date and comprehensive data on each chronobiotic. Furthermore, the biological and pharmacological relevance of the database will be augmented through synchronization with additional resources, including the FDA. In cases of overlapping data, compound cards will highlight the unique properties of each chronobiotic, thereby providing a robust and multifaceted resource for researchers and practitioners in the field. Full article

Aerobic exercise (AE) modulates vascular function through hemodynamic responses, thereby influencing cardiovascular health and risk, with the circadian rhythm system playing a crucial role. This chronobiological study investigated diurnal variations in exercise-induced hemodynamic changes in the common carotid artery. In a randomized crossover trial, twenty-two sedentary adults completed eight AE interventions (one per laboratory visit day), with each session performed at one of eight evenly distributed time points (from 06:00 to 20:00). Vascular ultrasound imaging and hemodynamic parameter calculations were performed both pre- and post-exercise. Compared to other time points, AE at 06:00 and 18:00 induced a greater and more sustained increase in mean flow rate and wall shear stress (WSS). Moreover, AE at 06:00 was associated with a smaller increase in oscillatory shear index and a larger decrease in peripheral resistance compared to other time points. Exercise-induced hemodynamic responses exhibited significant temporal variations. These findings emphasize the importance of exercise timing in optimizing vascular benefits for sedentary individuals. Full article

Background: In systemic sclerosis (SSc), endothelial dysfunction, inflammation, and reduced nitric oxide levels may disrupt circadian blood pressure (BP) regulation. There are studies showing that inflammatory and certain other cells in diseases like SSc exhibit diurnal rhythms. In our study, we examined the effect of SSc on BP. In particular, the frequency of the non-dipper pattern (lack of nighttime BP reduction) in SSc patients has not been adequately investigated. The aim of this study was to evaluate the 24 h BP profile in SSc patients and to compare the frequency of the non-dipper pattern with that of the non-scleroderma group. Additionally, the identification of disrupted circadian BP patterns in SSc patients aims to contribute to the development of personalized, time-sensitive BP monitoring strategies in the future and to support the applicability of personalized medicine in this context. Methods: A total of 31 SSc patients diagnosed according to the 2013 ACR/EULAR classification criteria and 30 age- and sex-matched individuals without SSc were included in this prospective study. BP changes between day and night were evaluated by measuring BP every 30 min with a 24 h ambulatory blood pressure monitoring (ABPM) device. The non-dipper pattern was defined as a decrease in BP of less than 10% during the night compared to the day. To better assess BP fluctuations during the night, nighttime measurements were divided into two time periods: first, 24:00–04:00, and then 04:00–08:00. Additionally, laboratory and clinical parameters and SSc subtypes were compared between the groups. Results: The ABPM findings were compared between the groups with and without SSc. The non-dipper pattern was significantly more common in the SSc group at all time intervals. The non-dipper pattern was observed in 25.8% of the non-SSc group and 83.9% of SSc patients (p < 0.001). In the period between 24:00 and 04:00, the prevalence was 25.8% in the control group and 71.0% in SSc patients (p < 0.001), and between 04:00 and 08:00, it was 35.5% in the control group and 80.6% in SSc patients (p < 0.001). No significant difference was found in non-dipper patterns between individuals with diffuse and limited cutaneous forms of systemic sclerosis. Conclusions: The non-dipper BP pattern is significantly more common in patients with SSc, indicating the disruption of the circadian rhythm affecting BP. Analysis performed by dividing the night into specific time periods revealed that this deterioration continued throughout the night. The findings highlight the importance of circadian BP monitoring in SSc patients and may contribute to future risk stratification and treatment strategies. Circadian BP analysis in SSc may help to develop strategies that are personalized for these patients and tailored to their physiological rhythm. Full article

Schizophrenia is a psychiatric disorder characterized by positive, negative, and cognitive symptoms. MK-801, an N-methyl-D-aspartate receptor antagonist, has been used to induce schizophrenia-like behaviors in animal models. Here, we employed IntelliCage, an automated system used for tracking behavior, to assess schizophrenia-like behaviors in MK-801-treated mice under semi-naturalistic conditions. Mice that had been treated with MK-801 for 2 weeks were analyzed for locomotion, emotional, and cognitive functions. Repeated MK-801-treated mice exhibited transient hyperactivity in a novel environment, without significant changes in overall circadian activity. Sucrose preference remained intact, suggesting preserved reward sensitivity. However, less time spent in the corner during the early phase of the competition test indicated reduced competitive behavior for limited water rewards. In the behavioral flexibility test, repeated MK-801-treated mice showed impaired reversal learning, suggesting reduced cognitive flexibility, although the acquisition of initial place discrimination was comparable to that observed in control mice. These behavioral impairments parallel core symptoms of schizophrenia, particularly in the social and cognitive domains. Our findings demonstrate the utility of IntelliCage in detecting behavioral phenotypes over prolonged periods in group-housed settings. This study provides an ecologically valid platform for assessing schizophrenia-like behaviors and may facilitate the development of translationally relevant therapeutic interventions. Full article

Multisensory integration is fundamental for coherent perception and interaction with the environment. While cortical mechanisms of multisensory convergence are well studied, emerging evidence implicates specialized retinal ganglion cells—particularly melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs)—in crossmodal processing. This review explores how hierarchical brain networks (e.g., superior colliculus, parietal cortex) and ipRGCs jointly shape perception and behavior, focusing on their convergence in multisensory plasticity. We highlight ipRGCs as gatekeepers of environmental light cues. Their anatomical projections to multisensory areas like the superior colliculus are well established, although direct evidence for their role in human audiovisual integration remains limited. Through melanopsin signaling and subcortical projections, they may modulate downstream multisensory processing, potentially enhancing the salience of crossmodal inputs. A key theme is the spatiotemporal synergy between melanopsin and melatonin: melanopsin encodes light, while melatonin fine-tunes ipRGC activity and synaptic plasticity, potentially creating time-sensitive rehabilitation windows. However, direct evidence linking ipRGCs to audiovisual rehabilitation remains limited, with their role primarily inferred from anatomical and functional studies. Future implementations should prioritize quantitative optical metrics (e.g., melanopic irradiance, spectral composition) to standardize light-based interventions and enhance reproducibility. Nonetheless, we propose a translational framework combining multisensory stimuli (e.g., audiovisual cues) with circadian-timed melatonin to enhance recovery in visual disorders like hemianopia and spatial neglect. By bridging retinal biology with systems neuroscience, this review redefines the retina’s role in multisensory processing and offers novel, mechanistically grounded strategies for neurorehabilitation. Full article

The importance of sleep has been reported for decades. Epilepsy is a heterogeneous disorder comprising multiple elements that might influence sleep and wakefulness. Notably, animal studies show disruptions of the circadian molecular system in different models of epilepsy, along with altered rest–activity and other circadian rhythms. So far, studies of molecular circadian systems in people with epilepsy are lacking, prompting further research. Seizures—the primary and most debilitating symptom of epilepsy—and interictal activity disrupt regular sleep and sleep–wake rhythms. Alterations in one’s sleep structure are seen in both drug-naïve and drug-resistant patients with epilepsy. In particular, low sleep efficiency, a reduction in total sleep time, and changes in sleep stages were found in both homogenous and mixed samples of epilepsy patients. Both ictal and interictal activity were also shown to be associated with changes in peripheral circadian phase biomarkers such as melatonin and cortisol. Moreover, epilepsy comorbidities, antiseizure medications, and a variety of syndromes can be a cause of sleep problems or even sleep disorders. Sleep disorders vary depending on various comorbidities and syndromes, and encompass all major groups of sleep disorders defined in the International Classification of Sleep Disorders. Controversial findings on the effects of various antiseizure medications were found in the literature. However, medications such as benzodiazepines, gabapentinoids, and barbiturates are particularly associated with excessive daytime sleepiness. Overall, a sleep evaluation must be included in the management of every patient with epilepsy. Full article

Background: This study aimed to develop a model for understanding stress-induced sleep disturbances and to explore the potential interactions between sleep disturbances and mood disturbances. Methods: The chronic unpredictable mild stress (CUMS) group was established using the CUMS method, while the CUMS+Noise group was subjected to an additional 8-h exposure to noise in conjunction with the CUMS protocol. Each group was tested for anxiety and depressive-like behavior using the open-field, elevated plus maze, tail suspension, and forced swimming tests in male C57BL/6J mice. Subsequently, we assessed sleep status using sleep recordings and a standardized scoring system alongside the pentobarbital sodium-induced sleep test. Results: The mice in both model groups exhibited anxiety-like behavior. Sleep disturbances observed in the CUMS+Noise group were characterized by disruptions in sleep duration and circadian rhythm. This observation was supported by a marked reduction in multiple sleep time intervals and single sleep duration, as well as a significant increase in sleep duration at the final time interval of ZT23-24. To further investigate the potential mechanisms of interaction, we conducted an analysis of hub genes present in the hippocampal sequencing data utilizing weighted gene co-expression network analysis (WGCNA). Pearson correlation analysis revealed a significant association between the hub genes Alb, P2rx1, and Npsr1 and key phenotypic traits. However, PCR experiments indicated that only Alb showed a significant difference, which aligns with the sequencing results. Conclusions: Albumin is a crucial transporter protein for thyroid hormones and plays a vital role in their metabolism. The interaction between sleep disorders and anxiety-like behavior may be closely linked to the dysfunctional transportation of thyroid hormones by albumin. Full article

The absence of standardized time zones has profound implications, influencing social, economic, and energy dynamics. It also disrupts personal aspects, such as sleep patterns and family routines. One specific dimension of this issue is the transition to daylight saving time (DST), which entails shifting between standard time (winter) and daylight saving time (summer). This practice has sparked global debates due to its varying impacts across regions and sectors. Although DST primarily aims to optimize energy consumption by leveraging natural daylight, much attention has focused on its broader societal effects. However, the energy performance of commercial buildings under DST remains an underexplored yet equally significant area. This article presents a literature review to critically evaluate the effects of the winter-to-summer time shift on commercial buildings, concentrating on three key factors: energy consumption, where seasonal variations in lighting, heating, and cooling demands may alter anticipated energy savings; occupant thermal comfort, as time changes can disrupt the circadian rhythms of building occupants, impacting productivity and well-being; and operational considerations, as building systems like HVAC and automated controls must adjust to shifting daylight schedules. Accordingly, this review seeks to offer a comprehensive understanding of how the winter–summer time transition affects commercial buildings by analyzing energy consumption patterns, occupant comfort levels, and operational challenges. In doing so, it contributes to optimizing building management practices under varying daylight conditions to enhance energy efficiency and occupant satisfaction. Full article

Circadian rhythms are innate biological systems that control everyday behavior and physiology. Furthermore, bilateral interaction between the host’s circadian rhythm and the gut microbes influences a variety of health ramifications, including metabolic diseases, obesity, and mental health including GALT physiology and the microbiome population. Therefore, we are studying the correlation between differential gene expression in the chicken brain and microbiota abundance during circadian rhythms. To understand this, we raised freshly hatched chicks under two photoperiod treatments: normal photoperiod (NP = 12/12 LD) and extended photoperiod (EP 23/1 LD). The chicks were randomly assigned to one of two treatments. After 21 days of circadian entrainment, the chicks were euthanized at nine time points spaced six hours apart over 48 h to characterize the brain transcriptomes. Each sample’s RNA was extracted, and 36 mRNA libraries were generated and sequenced using Illumina technology, followed by data processing, count data generation, and differential gene expression analysis. We generated an average of 17.5 million reads per library for 237.9 M reads. When aligned to the Galgal6 reference genome, 11,867 genes had detectable expression levels, with a common dispersion value of 0.105. To identify the genes that follow 24 h rhythms, counts per million data were performed in DiscoRhythm. We discovered 577 genes with Cosinor and 417 with the JTK cycle algorithm that exhibit substantial rhythms. We used weighted gene co-expression network analysis (WGCNA) to analyze the correlation between differentially expressed genes and microbiota abundance. The most enriched pathways included aldosterone-regulated sodium reabsorption, endocrine and other factor-regulated calcium reabsorption, GABAergic synapse, oxidative phosphorylation, serotonergic synapse, dopaminergic synapse and circadian entrainment. This study builds on our previous study, and adds new findings about the specific interactions and co-regulation of the brain transcriptome and the gut microbiota. The interaction between gut microbiota and host gene expression highlights the potential benefits of microbiome-modulation approaches to improve gut health and performance in poultry. Full article