The prevalence of night-shift employment is on the rise among full-time and part-time workers globally. Those engaged in night-shift work encounter various biological challenges, including exposure to artificial light during nighttime and disruptions to their circadian rhythms. These factors, along with changes in daily routines and activities, may pose significant risks to the health of night workers. Notably, the number of individuals working overtime or on night shifts has increased across various sectors, particularly in transportation, healthcare, and manufacturing. The International Agency for Research on Cancer (IARC) has classified night-shift work as probably carcinogenic to humans (IARC Group 2A). Subsequent research has identified several potential mechanisms through which night-shift work may contribute to carcinogenicity: (1) disruption of circadian rhythms, (2) suppression of melatonin levels due to nighttime light exposure, (3) physiological alterations, (4) lifestyle changes, and (5) reduced vitamin D levels resulting from inadequate sunlight exposure. Colorectal cancer (CRC) poses a significant public health challenge, ranking as the second leading cause of cancer-related death worldwide in 2020. Other than CRC, other gastrointestinal cancers are also creating a great global health issue because of their morbidity and mortality rates. In this review, we highlight the role of night shifts in disturbing circadian rhythm and how this action leads to carcinogenesis in the GI tract.

A potential association of endogenous circadian rhythm disruption with risk of cancer development has been suggested, however, epidemiological evidence for the association of sleep traits with colorectal cancer (CRC) is limited and often contradictory. Here we investigated whether genetically predicted chronotype, insomnia and sleep duration are associated with CRC risk in males, females and overall and according to CRC anatomical subsites using Mendelian randomization (MR). The two-sample inverse variance weighted (IVW) method was applied using summary-level data in up to 58,221 CRC cases and 67,694 controls and genome-wide association data of genetic variants for self-reported sleep traits. Secondary analyses using alternative instruments and sensitivity analyses assessing potential violations of MR assumptions were conducted. Genetically predicted morning preference was associated with 13% lower risk of CRC in men (ORIVW = 0.87, 95% CI = 0.78, 0.97, P = 0.01), but not in women or in both sexes combined. Τhis association remained consistent in some, but not all, sensitivity analyses and was very similar for colon and rectal cancer. There was no evidence of an association for any other sleep trait. Overall, this study provides little to no evidence of an association between genetically predicted sleep traits and CRC risk.

Research linking circadian dysregulation to cancer development has received increasing attention recently. However, a comprehensive understanding of research hotspots and trends in this area remains limited. International studies on the circadian rhythms in cancer were retrieved and downloaded from the Web of Science database. Bibliometric analysis and visualization were performed using VOSviewer, CiteSpace, and HistCite. Three thousand three hundred and eighteen English articles from 2004 to 2024 were screened and evaluated. The increase in publications and citations reflected the rapid expansion of the field. Scholars and institutions in the United States have relatively high academic productivity and impact. Chronobiology International is the most popular journal. Key clustering analysis identified six themes: biochemistry and molecular biology, physiology and immunomodulation, night shift work and health effects, physiological and mental health, tumor therapy research, and oxidative stress and cancer-related mechanisms. Keyword burst analysis identified the regulation of circadian rhythms on cells and tumor microenvironment as the research frontiers. The role of circadian rhythms in tumor immunotherapy was a current research hotspot identified by reference co-citation clustering analysis. This study reveals the current status of research on the circadian rhythms in cancer and predicts future trends. These findings provide new ideas for developing novel cancer prevention and treatment strategies.

Circadian rhythms are important cellular pathways first described for their essential role in helping organisms adjust to the 24 h day-night cycle and synchronize physiological and behavioral functions. Most organisms have evolved a circadian central clock to anticipate daily environmental changes in light, temperature, and mate availability. It is now understood that multiple clocks exist in organisms to regulate the functions of specific organs. Epidemiological studies in humans reported that disruption of the circadian rhythms caused by sleep deprivation is linked to the onset of immune-related conditions, suggesting the importance of circadian regulation of immunity. Mechanistic studies to define how circadian clocks and immune responses interact have profound implications for human health. However, elucidating the clocks and their tissue-specific functions has been challenging in mammals. Many studies using simple model organisms such as Drosophila melanogaster have been pioneering in discovering that the clock controls innate immune responses and immune challenges can impact circadian rhythms and/or their outcomes. In this review, we will report genetic studies using the humble fruit fly that identified the existence of reciprocal interactions between the circadian pathway and innate immune signaling, contributing to elucidate mechanisms in the growing field of chrono-immunology.

Skin cutaneous melanoma (SKCM) is a highly aggressive and malignant tumor that arises from the malignant transformation of melanocytes. In light of the limitations of existing treatment modalities, there is a pressing need to identify new drug targets for SKCM. Aryl-hydrocarbon receptor nuclear translocator-like (ARNTL), also known as Bmal1, is a gene that has been linked to the onset and progression of cancer. However, its role in SKCM remains understudied.

The expression of Bmal1 mRNA and protein was detected using TCGA, GTEx, CCLE, and ULCAN databases. Moreover, survival analysis was performed to investigate the association between Bmal1 and immune invasion and gene expression in immune infiltrating cells via CIBERSORT, R programming, TIMER, Sangerbox, Kaplan-Meier. The study also explored the role of proteins associated with Bmal1 by using R programming and databases (STRING and GSEA). Both in vitro and in vivo studies were conducted to examine the potential role of Bmal1 in SKCM.

Compared to normal tissues, the expression level of Bmal1 was significantly reduced in SKCM. Which has been associated with its poor prognosis. Similarly, its expression in SKCM was substantially correlated with immune infiltration, while biogenic analysis indicated that it could potentially influence the tumor immune microenvironment (TME) by influencing tumor-associated neutrophils (TANs). Moreover, Bmal1 overexpression suppressed the proliferation and invasion of melanoma cells and enhanced apoptosis, migration, and cell colony formation.

This study concluded that Bmal1 is a novel biomarker that functions as both a diagnostic and prognostic indicator for the progression of SKCM.

Abnormal growth of blood vessels (choroidal neovascularization) can lead to age-related macular degeneration (AMD) and eventually cause vision loss due to detachment of the retinal pigmented epithelium. This indicates that choroidal neovascularization is important for the treatment of AMD. The circadian clock in the mammalian retina is responsible for controlling various functions of the retina, enabling it to adjust to changes in light and darkness. Recent studies have revealed a potential connection between the circadian clock and eye diseases, although a cause-and-effect relationship has not been definitively established. C57BL/6J male mice (aged 6 weeks) were randomly divided into two groups (Control group: 9:00-21:00 light period (300 lx); Jet lag group: 8-hour phase advance once every 4 days). A laser-induced CNV model was created after 2 weeks of feeding in a controlled or jet-lagged environment. Then, full transcriptome sequencing was performed. The pathways regulated by differentially expressed mRNAs were identified by GO analysis and GSEA. Further protein networks were constructed with the STRING database and Cytoscape software. WGCNA was used to further explore the co-expression modules of these differential genes and the correlation between these differential genes and phenotypes. ceRNA networks were constructed with miRanda and TargetScan. The pathways associated with the overlapping differentially expressed mRNAs in the ceRNA network were identified, and the hub genes were validated by qPCR. A total of 661 important DEGs, 31 differentially expressed miRNAs, 106 differentially expressed lncRNAs and 87 differentially expressed circRNAs were identified. GO and GSEA showed that the upregulated DEGs were mainly involved in reproductive structure development and reproductive system development. The STRING database and Cytoscape were used to determine the protein interaction relationships of these DEGs. WGCNA divided the expression of these genes into several modules and screened the hub genes of each module separately. Furthermore, a ceRNA network was constructed. GO analysis and GSEA showed that these target DEmRNAs mainly function in wound healing, cell spreading, epiboly involved in wound healing, epiboly, and morphogenesis of an epithelial sheet. Finally, ten key genes were identified, and their expression patterns were confirmed by real-time qPCR. In this study, we investigated the regulatory mechanism of ceRNAs in choroidal neovascularization according to different light-dark cycles in the eyeball.

Circadian rhythms are approximately 24-hour cycles in physiological and behavioral processes. They are entrained to the external solar day via blue wavelength light. Disruptions in these intrinsic rhythms can lead to circadian dysfunction, which has several negative implications on human health, including cancer development and progression.

Here we review the molecular mechanisms of circadian disruption and their impact on tumor development and progression, discuss the interplay between circadian dysfunction and cancer in basic scientific studies and clinical data, and propose the potential clinical implications of these data that may be used to improve patient outcomes and reduce cost of treatment.

Using scientific literature databases, relevant studies were analyzed to draw overarching conclusions of the relationship between circadian rhythm dysruption and cancer.

Circadian disruption can be mediated by a number of environmental factors such as exposure to light at night, shift work, jetlag, and social jetlag which drive oncogenesis. Tumor growth and progression, as well as treatment, can lead to long-term alterations in circadian rhythms that negatively affect quality of life in cancer survivors.

Diet is a robust entrainment cue that regulates diurnal rhythms of the gut microbiome. We and others have shown that disruption of the circadian clock drives the progression of colorectal cancer (CRC). While certain bacterial species have been suggested to play driver roles in CRC, it is unknown whether the intestinal clock impinges on the microbiome to accelerate CRC pathogenesis. To address this, genetic disruption of the circadian clock, in an Apc-driven mouse model of CRC, was used to define the impact on the gut microbiome. When clock disruption is combined with CRC, metagenomic sequencing identified dysregulation of many bacterial genera including Bacteroides, Helicobacter, and Megasphaera. We identify functional changes to microbial pathways including dysregulated nucleic acid, amino acid, and carbohydrate metabolism, as well as disruption of intestinal barrier function. Our findings suggest that clock disruption impinges on microbiota composition and intestinal permeability that may contribute to CRC pathogenesis.

Metastasis is the major culprit of treatment failure in nasopharyngeal carcinoma (NPC). Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2), a core circadian gene, plays a crucial role in the development of various tumors. Nevertheless, the biological role and mechanism of ARNTL2 are not fully elucidated in NPC. In this study, ARNTL2 expression was significantly upregulated in NPC tissues and cells. Overexpression of ARNTL2 facilitated NPC cell migration and invasion abilities, while inhibition of ARNTL2 in similarly treated cells blunted migration and invasion abilities in vitro. Consistently, in vivo xenograft tumor models revealed that ARNTL2 silencing reduced nude mice inguinal lymph node and lung metastases, as well as tumor growth. Mechanistically, ARNTL2 negatively regulated the transcription expression of AMOTL2 by directly binding to the AMOTL2 promoter, thus reducing the recruitment and stabilization of AMOTL2 to LATS1/2 kinases, which strengthened YAP nuclear translocation by suppressing LATS-dependent YAP phosphorylation. Inhibition of AMOTL2 counteracted the effects of ARNTL2 knockdown on NPC cell migration and invasion abilities. These findings suggest that ARNTL2 may be a promising therapeutic target to combat NPC metastasis and further supports the crucial roles of circadian genes in cancer development.

Despite past research linking HLF mutations to cancer development, no pan-cancer analyses of HLF have been published. As a result, we utilized multiple databases to illustrate the potential roles of HLF in diverse types of cancers. Several databases were used to assess HLF expression in the TCGA cancer samples. Additional assessments were undertaken to investigate the relationship between HLF and overall survival, immune cell infiltration, genetic alterations, promoter methylation, and protein-protein interaction. HLF's putative roles and the relationship between HLF expression and drug reactivity were investigated. HLF expression was shown to be lower in tumor tissues from a variety of malignancies when compared to normal tissues. There was a substantial link found between HLF expression and patient survival, genetic mutations, and immunological infiltration. HLF influenced the pathways of apoptosis, cell cycle, EMT, and PI3K/AKT signaling. Abnormal expression of HLF lowered sensitivity to numerous anti-tumor drugs and small compounds. According to our findings, reduced HLF expression drives cancer growth, and it has the potential to be identified as a vital biomarker for use in prognosis, immunotherapy, and targeted treatment of a range of malignancies.

Associations between subjective sleep quality and stage-specific heart rate (HR) may have important clinical relevance when aiming to optimize sleep and overall health. The majority of previously studies have been performed during short periods under laboratory-based conditions. The aim of this study was to investigate the associations of subjective sleep quality with heart rate during REM sleep (HR REMS) and non-REM sleep (HR NREMS) using a wearable device (Fitbit Versa).

This is a secondary analysis of data from the intervention group of a randomized controlled trial (RCT) performed between December 3, 2018, and March 2, 2019, in Tokyo, Japan. The intervention group consisted of 179 Japanese office workers with metabolic syndrome (MetS), Pre-MetS or a high risk of developing MetS. HR was collected with a wearable device and sleep quality was assessed with a mobile application where participants answered The St. Mary's Hospital Sleep Questionnaire. Both HR and sleep quality was collected daily for a period of 90 days. Associations of between-individual and within-individual sleep quality with HR REMS and HR NREMS were analyzed with multi-level model regression in 3 multivariate models.

The cohort consisted of 92.6% men (n=151) with a mean age (± standard deviation) of 44.1 (±7.5) years. A non-significant inverse between-individual association was observed for sleep quality with HR REMS (HR REMS -0.18; 95% CI -0.61, 0.24) and HR NREMS (HR NREMS -0.23; 95% CI -0.66, 0.21), in the final multivariable adjusted models; a statistically significant inverse within-individual association was observed for sleep quality with HR REMS (HR REMS -0.21 95% CI -0.27, -0.15) and HR NREMS (HR NREMS -0.21 95% CI -0.27, -0.14) after final adjustments for covariates.

The present study shows a statistically significant within-individual association of subjective sleep quality with HR REMS and HR NREMS. These findings emphasize the importance of considering sleep quality on the individual level. The results may contribute to early detection and prevention of diseases associated with sleep quality which may have important implications on public health given the high prevalence of sleep disturbances in the population.

Shift work has been found to disrupt the circadian system, leading to negative health effects. The objective of this study was to assess the progress and frontiers in research on the health-related influence of shift work. The study analyzed 3,696 data points from Web of Science, using the bibliometric software CiteSpace to visualize and analyze the field. The results showed a steady increase in annual publications, particularly in the last 5 years, with a rapid increase in publications from China. The United States contributed the most to the number of publications and worldwide collaborations. The most prolific institution and author were the Brigham and Women's Hospital and Professor Bjorn Bjorvatn, respectively. The Journal of Chronobiology International ranked at the top and focused primarily on shift worker research. In the first decade of study, the primary focus was on the associations between shift work and cardiovascular disease and metabolic disorders. Over time, research on the health effects of shift work has expanded to include cancer and mental health, with subsequent studies investigating molecular mechanisms. This study provides a comprehensive and intuitive analysis of the negative health impacts of shift work. It highlights existing research hotspots and provides a roadmap for future studies. Further research is needed to explore the adverse health consequences and related mechanisms of shift work exposure, as well as interventions to mitigate its health effects.

Circadian rhythm is an internal timing system and harmonizes a variety of cellular, behavioral, and physiological processes to daily environment. Circadian disturbance caused by altered life style or disrupted sleep patterns inevitably contributes to various disorders. As the rapidly increased cancer occurrences and subsequent tremendous financial burdens, more researches focus on reducing the morbidity rather than treating it. Recently, many epidemiologic studies demonstrated that circadian disturbance was tightly related to the occurrence and development of cancers. For urinary system, numerous clinical researches observed the incidence and progress of prostate cancer were influenced by nightshift work, sleep duration, chronotypes, light exposure, and meal timing, this was also proved by many genetic and fundamental findings. Although the epidemiological studies regarding the relationship between circadian disturbance and kidney/bladder cancers were relative limited, some basic researches still claimed circadian disruption was closely correlated to these two cancers. The role of circadian chemotherapy on cancers of prostate, kidney, and bladder were also explored, however, it has not been regularly recommended considering the limited evidence and poor standard protocols. Finally, the researches for the impacts of circadian disturbance on cancers of adrenal gland, penis, testis were not found at present. In general, a better understanding the relationship between circadian disturbance and urological cancers might help to provide more scientific work schedules and rational lifestyles which finally saving health resource by reducing urological tumorigenesis, however, the underlying mechanisms are complex which need further exploration.

The circadian clock controls the expression of a large proportion of protein-coding genes in mammals and can modulate a wide range of physiological processes. Recent studies have demonstrated that disruption or dysregulation of the circadian clock is involved in the development and progression of several diseases, including cancer. The cell cycle is considered to be the fundamental process related to cancer. Accumulating evidence suggests that the circadian clock can control the expression of a large number of genes related to the cell cycle. This article reviews the mechanism of cell cycle-related genes whose chromatin regulatory elements are rhythmically occupied by core circadian clock transcription factors, while their RNAs are rhythmically expressed. This article further reviews the identified oscillatory cell cycle-related genes in higher organisms such as baboons and humans. The potential functions of these identified genes in regulating cell cycle progression are also discussed. Understanding how the molecular clock controls the expression of cell cycle genes will be beneficial for combating and treating cancer.

Biological rhythms have a crucial role in shaping the biology and ecology of organisms. Light pollution is known to disrupt these rhythms, and evidence is emerging that chemical pollutants can cause similar disruption. Conversely, biological rhythms can influence the effects and toxicity of chemicals. Thus, by drawing insights from the extensive study of biological rhythms in biomedical and light pollution research, we can greatly improve our understanding of chemical pollution. This Essay advocates for the integration of biological rhythmicity into chemical pollution research to gain a more comprehensive understanding of how chemical pollutants affect wildlife and ecosystems. Despite historical barriers, recent experimental and technological advancements now facilitate the integration of biological rhythms into ecotoxicology, offering unprecedented, high-resolution data across spatiotemporal scales. Recognizing the importance of biological rhythms will be essential for understanding, predicting, and mitigating the complex ecological repercussions of chemical pollution.

This case-control study investigated the relationship between sleep duration and quality with the occurrence of breast cancer among women, both pre- and post-menopausal, in the northwest Khyber Pakhtunkhwa (KP) region of Pakistan.

This case-control research was carried in multiple tertiary care facilities. Newly diagnosed primary breast cancer patients were recruited as cases (n = 408), and 5+ years age-matched controls (n = 408) were randomly selected from the general population. Participants completed a Pittsburg sleeping quality index (PSQI) questionnaire that included questions on sleep characteristics. Statistical analysis included independent t-tests to compare mean sleep durations and quality scores between groups, and logistic regression to adjust for potential confounders.

Sleep onset latency between cases and controls was not significantly associated with health outcomes, with a P-value of .142. However, sleep duration showed a significant association (P = .049). For sleep duration, the adjusted odds ratio for ≤6 h was 1.02 (95% CI: .5-2.1), while for 7-8 h the adjusted odds ratio was 1.0 (95% CI: .6-1.6). Self-reported sleep quality did not demonstrate significant associations, with the P-value for "very good" sleep quality being .561. Sleep duration of less than 6 h among women with triple-negative breast cancer (TNBC) was found to be strongly associated with a more aggressive type of breast cancer, with an adjusted odds ratio of 1.5 (95% CI: 1.02-2.3, P < .05).

This study does not provide evidence to support an association between sleep duration or quality and the risk of breast cancer. However, it reports a significant association, with shorter sleep durations linked to an increased risk particularly in the context of aggressive breast cancer types such as TNBC.

The homeostasis of the gut microbiota and circadian rhythm is critical to host health, and both are inextricably intertwined with lung cancer. Although time-restricted feeding (TRF) can maintain circadian synchronization and improve metabolic disorders, the effects of TRF on the fecal microbiome, metabolome and their diurnal oscillations in lung cancer have not been discussed. We performed 16S rRNA sequencing and untargeted metabonomic sequencing of the feces prepared from models of tumor-bearing BALB/c nude mice and urethane-induced lung cancer. We demonstrated for the first time that TRF significantly delayed the growth of lung tumors. Moreover, TRF altered the abundances of the fecal microbiome, metabolome and circadian clocks, as well as their rhythmicity, in lung cancer models of tumor-bearing BALB/c nude mice and/or urethane-induced lung cancer C57BL/6J mice. The results of fecal microbiota transplantation proved that the antitumor effects of TRF occur by regulating the fecal microbiota. Notably, Lactobacillus and Bacillus were increased upon TRF and were correlated with most differential metabolites. Pathway enrichment analysis of metabolites revealed that TRF mainly affected immune and inflammatory processes, which might further explain how TRF exerted its anticancer benefits. These findings underscore the possibility that the fecal microbiome/metabolome regulates lung cancer following a TRF paradigm.

A wide variety of liver functions are regulated daily by the liver circadian clock and via systemic circadian control by other organs and cells within the gastrointestinal tract as well as the microbiome and immune cells. Disruption of the circadian system, as occurs during jetlag, shift work or an unhealthy lifestyle, is implicated in several liver-related pathologies, ranging from metabolic diseases such as obesity, type 2 diabetes mellitus and nonalcoholic fatty liver disease to liver malignancies such as hepatocellular carcinoma. In this Review, we cover the molecular, cellular and organismal aspects of various liver pathologies from a circadian viewpoint, and in particular how circadian dysregulation has a role in the development and progression of these diseases. Finally, we discuss therapeutic and lifestyle interventions that carry health benefits through support of a functional circadian clock that acts in synchrony with the environment.

Adolescents are an at-risk group for circadian misalignment. The contribution of sleep-wake rhythm instability to the psychoemotional, cognitive, and weight disorders of adolescents has been studied in sufficient detail. At the same time, there is insufficient information about the association between chrononutrition indices and the well-being of adolescents. The aim of this study is to investigate the relationship between chrononutrition indices and academic achievement, psychoemotional state, and anthropometric indicators in adolescents. The study involved 12,759 students in grades 6-11 of secondary schools, aged 14.2 ± 1.7 years old; 57.2% of whom were girls. Participants provided personal data, frequency and time of meals during the day and at night, on weekdays and weekends, and completed the Zung Self-Rating Depression Scale and the Yale Food Addiction Scale. There is a U-shaped association between eating mid-phase (EPFc), eating jetlag (EJL), and eating window (EW) with GPA, ZSDSI, and FA. At the same time, the frequency of night eating (NE) is linearly associated with the studied parameters. NE is the strongest predictor of ZSDSI (β = 0.24), FA (β = 0.04), and GPA (β = -0.22). EPFc, EJL, and EW practically do not differ in the strength of their association with the studied indicators. ZSDSI is most closely associated with the chrononutrition indices. There is a weak negative association between BMI and EW (β = -0.03) and NE (β = -0.04). Thus, circadian eating disorders are more often observed in adolescents with poor academic performance, high levels of depression, and food addiction.

The circadian timing system enables organisms to adapt their physiology and behavior to the cyclic environmental changes including light-dark cycle or food availability. Misalignment between the endogenous circadian rhythms and external cues is known as chronodisruption and is closely associated with the development of metabolic and gastrointestinal disorders, cardiovascular diseases, and cancer. Time-restricted eating (TRE, in human) is an emerging dietary approach for weight management. Recent studies have shown that TRE or time-restricted feeding (TRF, when referring to animals) has several beneficial health effects, which, however, are not limited to weight management. This review summarizes the effects of TRE/TRF on regulating energy metabolism, gut microbiota and homeostasis, development of cardiovascular diseases and cancer. Furthermore, we will address the role of circadian clocks in TRE/TRF and propose ways to optimize TRE as a dietary strategy to obtain maximal health benefits.

We sought to quantify the effects of in-house call(IHC) on sleep patterns and burnout among acute care surgeons (ACS).

Many ACS take INC, which leads to disrupted sleep and high levels of stress and burnout.

Physiological and survey data of 224 ACS with IHC were collected over 6 months. Participants continuously wore a physiological tracking device and responded to daily electronic surveys. Daily surveys captured work and life events as well as feelings of restfulness and burnout. The Maslach Burnout Inventory (MBI) was administered at the beginning and end of the study period.

Physiological data were recorded for 34,135 days, which includes 4389 nights of IHC. Feelings of moderate, very, or extreme burnout occurred 25.7% of days and feelings of being moderately, slightly, or not at all rested occurred 75.91% of days. Decreased amount of time since the last IHC, reduced sleep duration, being on call, and having a bad outcome all contribute to greater feelings of daily burnout ( P <0.001). Decreased time since last call also exacerbates the negative effect of IHC on burnout ( P <0.01).

ACS exhibit lower quality and reduced amount of sleep compared with an age-matched population. Furthermore, reduced sleep and decreased time since the last call led to increased feelings of daily burnout, accumulating in emotional exhaustion as measured on the MBI. A reevaluation of IHC requirements and patterns as well as identification of countermeasures to restore homeostatic wellness in ACS is essential to protect and optimize our workforce.

Previous research has reported that the gut microbiota performs an essential role in sleep through the microbiome-gut-brain axis. However, the causal association between gut microbiota and sleep remains undetermined.

We performed a two-sample, bidirectional Mendelian randomization (MR) analysis using genome-wide association study summary data of gut microbiota and self-reported sleep traits from the MiBioGen consortium and UK Biobank to investigate causal relationships between 119 bacterial genera and seven sleep-associated traits. We calculated effect estimates by using the inverse-variance weighted (as the main method), maximum likelihood, simple model, weighted model, weighted median, and MR-Egger methods, whereas heterogeneity and pleiotropy were detected and measured by the MR pleiotropy residual sum and outlier method, Cochran's Q statistics, and MR-Egger regression.

In forward MR analysis, inverse-variance weighted estimates concluded that the genetic forecasts of relative abundance of 42 bacterial genera had causal effects on sleep-associated traits. In the reverse MR analysis, sleep-associated traits had a causal effect on 39 bacterial genera, 13 of which overlapped with the bacterial genera in the forward MR analysis.

In conclusion, our research indicates that gut microbiota may be involved in the regulation of sleep, and conversely, changes in sleep-associated traits may also alter the abundance of gut microbiota. These findings suggest an underlying reciprocal causal association between gut microbiota and sleep.

Circadian clocks are pervasive throughout nature, yet only recently has this adaptive regulatory program been described in nonphotosynthetic bacteria. Here, we describe an inherent complexity in the Bacillus subtilis circadian clock. We find that B. subtilis entrains to blue and red light and that circadian entrainment is separable from masking through fluence titration and frequency demultiplication protocols. We identify circadian rhythmicity in constant light, consistent with the Aschoff's rule, and entrainment aftereffects, both of which are properties described for eukaryotic circadian clocks. We report that circadian rhythms occur in wild isolates of this prokaryote, thus establishing them as a general property of this species, and that its circadian system responds to the environment in a complex fashion that is consistent with multicellular eukaryotic circadian systems.

Cardiovascular disease (CVD) and cancer are leading causes of mortality and morbidity worldwide and are the major focus of the World Health Organization's joint prevention programs. While, diverse diseases, CVD and cancer, have many similarities. These include common lifestyle-related risk factors and shared environmental, metabolic, cellular, inflammatory, and genetic pathways. In this review, we will discuss the shared lifestyle-related and environmental risk factors central to both diseases and how the strategies commonly used to prevent atherosclerotic vascular disease can be applied to cancer prevention.

Animal and experimental studies suggest circadian disruption increases colorectal cancer risk, but evidence in humans is limited. We examined night shift work, chronotype, and residential position within a time zone, proxies for circadian disruption, in relation to colorectal cancer risk.

Participants in the Black Women's Health Study, a prospective cohort of 59,000 Black American women established in 1995, reported history of night shift work and chronotype on follow-up questionnaires. Residential position within a time zone was estimated using participant addresses at each questionnaire cycle. Number of colorectal cancer cases and follow-up duration varied by analysis depending on timing of exposure assessment, ranging from 204 over the 2005 to 2018 night shift work study period to 452 over the 1995 to 2018 residential position study period. Cox proportional hazards regression was used to estimate multivariable-adjusted HRs and 95% confidence intervals (CI).

Compared with never having worked a night shift, working a night shift for ≥10 years was associated with increased colorectal cancer risk (HR = 1.64; 95% CI, 1.01-2.66). However, shorter duration was not. The HR for evening versus morning chronotype was 0.96 (95% CI, 0.73-1.27). Westward position of residence within a time zone was not associated with colorectal cancer risk (HR per 5-degree longitude increase: 0.92; 95% CI, 0.82-1.03).

Our findings suggest a possible increased risk of colorectal cancer associated with long duration night shift work; however, results require confirmation in larger studies.

Circadian disruption from long-term night shift work may contribute to colorectal cancer development in Black women.

Renewal of retinal photoreceptor outer segments is conducted through daily shedding of distal photoreceptor outer segment tips and subsequent their phagocytosis by the adjacent retinal pigment epithelium (RPE) monolayer. Dysregulation of the diurnal clearance of photoreceptor outer segment tips has been implicated in age-related retinal degeneration, but it remains to be clarified how the circadian phagocytic activity of RPE cells is modulated by senescence. In this study, we used the human RPE cell line ARPE-19 to investigate whether hydrogen peroxide (H2O2)-induced senescence in ARPE-19 cells alters the circadian rhythm of their phagocytic activity. After synchronization of the cellular circadian clock by dexamethasone treatment, the phagocytic activity of normal ARPE-19 cells exhibited significant 24-h oscillation, but this oscillation was modulated by senescence. The phagocytic activity of senescent ARPE-19 cells increased constantly throughout the 24-h period, which still exhibited blunted circadian oscillation, accompanied by an alteration in the rhythmic expression of circadian clock genes and clock-controlled phagocytosis-related genes. The expression levels of REV-ERBα, a molecular component of the circadian clock, were constitutively increased in senescent ARPE-19 cells. Furthermore, pharmacological activation of REV-ERBα by its agonist SR9009 enhanced the phagocytic activity of normal ARPE-19 cells and increased the expression of clock-controlled phagocytosis-related genes. Our present findings extend to understand the role of circadian clock in the alteration of phagocytic activity in RPE during aging. Constitutive enhancement of phagocytic activity of senescent RPE may contribute to age-related retinal degeneration.

In modern society, there is a growing population affected by circadian clock disruption through night shift work, artificial light-at-night exposure, and erratic eating patterns. Concurrently, the rate of cancer incidence in individuals under the age of 50 is increasing at an alarming rate, and though the precise risk factors remain undefined, the potential links between circadian clock deregulation and young-onset cancers is compelling. To explore the complex biological functions of the clock, this review will first provide a framework for the mammalian circadian clock in regulating critical cellular processes including cell cycle control, DNA damage response, DNA repair, and immunity under conditions of physiological homeostasis. Additionally, this review will deconvolute the role of the circadian clock in cancer, citing divergent evidence suggesting tissue-specific roles of the biological pacemaker in cancer types such as breast, lung, colorectal, and hepatocellular carcinoma. Recent evidence has emerged regarding the role of the clock in the intestinal epithelium, as well as new insights into how genetic and environmental disruption of the clock is linked with colorectal cancer, and the molecular underpinnings of these findings will be discussed. To place these findings within a context and framework that can be applied towards human health, a focus on how the circadian clock can be leveraged for cancer prevention and chronomedicine-based therapies will be outlined.

The molecular machinery of the circadian clock regulates the expression of many genes and processes in the organism, allowing the adaptation of cellular activities to the daily light-dark cycles. Disruption of the circadian rhythm can lead to various pathologies, including cancer. Thus, disturbance of the normal circadian clock at both genetic and environmental levels has been described as an independent risk factor for cancer. In addition, researchers have proposed that circadian genes may have a tissue-dependent and/or context-dependent role in tumorigenesis and may function both as tumor suppressors and oncogenes. Finally, circadian clock core genes may trigger or at least be involved in different hallmarks of cancer. Hence, expanding the knowledge of the molecular basis of the circadian clock would be helpful to identify new prognostic markers of tumorigenesis and potential therapeutic targets.

Insufficient sleep syndrome, shift work disorder, and obstructive sleep apnea (OSA) not only significantly impact the health of affected individuals, but also pose a threat to public safety. This article describes the clinical manifestations and impact of these sleep disorders, particularly as they pertain to workers' health and those with safety-sensitive positions. Sleep deprivation, circadian rhythm disruptions, and excessive daytime sleepiness-hallmarks of insufficient sleep, shift work disorder, and OSA, respectively-all lead to a series of cognitive deficits and impaired concentration that affect workers in a wide variety of fields. We describe the health consequences of these disorders along with treatment strategies, with a focus on current regulatory standards and the under-recognition of OSA in commercial drivers. Given its large scale, there is a need for improved guidelines and regulations for the screening, diagnosis, treatment, and long-term follow-up of OSA in commercial motor vehicle drivers. Increased recognition of the ways in which these sleep disorders impact workers will pave the way for significant improvements in occupational health and safety.

Misalignment of the circadian clock compared to environmental cues causes circadian desynchrony, which is pervasive in humans. Clock misalignment can lead to various pathologies including obesity and diabetes, both of which are associated with pancreatic ductal adenocarcinoma - a devastating cancer with an 80% five-year mortality rate. Although circadian desynchrony is associated with an increased risk of several solid-organ cancers, the correlation between clock misalignment and pancreas cancer is unclear. Using a chronic jetlag model, we investigated the impact of clock misalignment on pancreas cancer initiation in mice harboring a pancreas-specific activated Kras mutation. We found that chronic jetlag accelerated the development of pancreatic cancer precursor lesions, with a concomitant increase in precursor lesion grade. Cell-autonomous knock-out of the clock in pancreatic epithelial cells of Kras-mutant mice demonstrated no acceleration of precursor lesion formation, indicating non-cell-autonomous clock dysfunction was responsible for the expedited tumor development. Therefore, we applied single-cell RNA sequencing over time and identified fibroblasts as the cell population manifesting the greatest clock-dependent changes, with enrichment of specific cancer-associated fibroblast pathways due to circadian misalignment.

Colorectal cancer (CRC) is third cancer causing death in the world. CRC is associated with disrupting the circadian rhythm (CR), closely associating the CRC progression and the dysregulation of genes involved in the biological clock. In this study, we aimed to understand the circadian rhythm changes in patients diagnosed with CRC. We used the GEO database with the ID GSE46549 for our analysis, which consists of 32 patients with CRC and one as normal control. Our study has identified five essential genes involved in CRC, HAPLN1, CDH12, IGFBP5, DCHS2, and DOK5, and had different enriched pathways, such as the Wnt-signaling pathway, at different time points of study. As a part of our study, we also identified various related circadian genes, such as CXCL12, C1QTNF2, MRC2, and GLUL, from the Circadian Gene Expression database, that played a role in circadian rhythm and CRC development. As circadian timing can influence the host tissue's ability to tolerate anticancer medications, the genes reported can serve as a potential drug target for treating CRC and become beneficial to translational settings.

Sleep, accounting for roughly one-third of a person's life, plays an important role in human health. Despite the close association between sleep patterns and medical diseases proven by several studies, it has been neglected in recent years. Presently, all societies are facing the most challenging health-threatening disease, cancer. Among all cancer types, gastrointestinal (GI) cancers, especially colorectal type, seem to be one of the most relevant to an individual's lifestyle; thus, they can be prevented by modifying behaviors most of the time. Previous studies have shown that disruption of the 24-h sleep-wake cycle increases the chance of colorectal cancer, which can be due to exposure to artificial light at night and some complex genetic and hormone-mediated mechanisms. There has also been some evidence showing the possible associations between other aspects of sleep such as sleep duration or some sleep disorders and GI cancer risk. This review brings some information together and presents a detailed discussion of the possible role of sleep patterns in GI malignancy initiation.

Glioblastoma (GBM) is one of the most aggressive tumors in the adult central nervous system. We previously revealed that circadian regulation of glioma stem cells (GSCs) affects GBM hallmarks of immunosuppression and GSC maintenance in a paracrine and autocrine manner. Here, we expand the mechanism involved in angiogenesis, another critical GBM hallmark, as a potential basis underlying CLOCK's pro-tumor effect in GBM. Mechanistically, CLOCK-directed olfactomedin like 3 (OLFML3) expression results in hypoxia-inducible factor 1-alpha (HIF1α)-mediated transcriptional upregulation of periostin (POSTN). As a result, secreted POSTN promotes tumor angiogenesis via activation of the TANK-binding kinase 1 (TBK1) signaling in endothelial cells. In GBM mouse and patient-derived xenograft models, blockade of the CLOCK-directed POSTN-TBK1 axis inhibits tumor progression and angiogenesis. Thus, the CLOCK-POSTN-TBK1 circuit coordinates a key tumor-endothelial cell interaction and represents an actionable therapeutic target for GBM.

Aims of this study were to test whether sleep fragmentation (SF) increased carcinogenesis and to investigate the possible mechanisms of carcinogenesis in a chemical-induced colon cancer model. In this study, eight-week-old C57BL/6 mice were divided into Home cage (HC) and SF groups. After the azoxymethane (AOM) injection, the mice in the SF group were subjected to SF for 77 days. SF was accomplished in a sleep fragmentation chamber. In the second protocol, mice were divided into 2% dextran sodium sulfate (DSS)-treated, HC, and SF groups and were exposed to the HC or SF procedures. Immunohistochemical and immunofluorescent stainings were conducted to determine the level of 8-OHdG and reactive oxygen species (ROS), respectively. Quantitative real-time polymerase chain reaction was used to assess the relative expression of inflammatory and ROS-generating genes. The number of tumors and average tumor size were significantly higher in the SF group than in the HC group. The intensity (%) of the 8-OHdG stained area was significantly higher in the SF group than in the HC group. The fluorescence intensity of ROS was significantly higher in the SF group than the HC group. SF accelerated cancer development in a murine AOM/DSS-induced model of colon cancer, and the increased carcinogenesis was associated with ROS- and oxidative stress-induced DNA damage.

In recent years, exceptional technological advances have enabled the identification and interrogation of rare circulating tumour cells (CTCs) from blood samples of patients, leading to new fields of research and fostering the promise for paradigm-changing, liquid biopsy-based clinical applications. Analysis of CTCs has revealed distinct biological phenotypes, including the presence of CTC clusters and the interaction between CTCs and immune or stromal cells, impacting metastasis formation and providing new insights into cancer vulnerabilities. Here we review the progress made in understanding biological features of CTCs and provide insight into exploiting these developments to design future clinical tools for improving the diagnosis and treatment of cancer.

Bladder cancer is the sixth most common cancer in the United States. Night shift work has previously been linked with cancer risk. Whether there is an association between rotating night shift work and bladder cancer in women has not been studied previously. Eligible participants in the Nurses' Health Study (NHS, n = 82,147, 1988-2016) and Nurses' Health Study II (NHSII, n = 113,630, 1989-2015) were prospectively followed and a total of 620 and 122 incident bladder cancer cases were documented during the follow-up of NHS and NHSII, respectively. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for bladder cancer incidence. We observed a significantly increased risk of bladder cancer among women with >5 years of night shift work history compared with women who never worked rotating night shifts in NHS (HR = 1.24; 95%CI = 1.01-1.54, p for trend = 0.06), but not in the pooled NHS and NHS II (HR = 1.18; 95%CI = 0.97-1.43, p for trend = 0.08). Secondary analyses stratified by smoking status showed no significant interaction (p = 0.89) between the duration of rotating night shift work and smoking status. In conclusion, our results did not provide strong evidence for an association between rotating night shift work and bladder cancer risk.

Light is an extrinsic factor that exerts widespread influence on the regulation of circadian, physiologic, hormonal, metabolic, and behavioral systems of all animals, including those used in research. These wide-ranging biologic effects of light are mediated by distinct photoreceptors, the melanopsin-containing intrinsically photosensitive retinal ganglion cells of the nonvisual system, which interact with the rods and cones of the conventional visual system. Here, we review the nature of light and circadian rhythms, current industry practices and standards, and our present understanding of the neurophysiology of the visual and nonvisual systems. We also consider the implications of this extrinsic factor for vivarium measurement, production, and technological application of light, and provide simple recommendations on artificial lighting for use by regulatory authorities, lighting manufacturers, designers, engineers, researchers, and research animal care staff that ensure best practices for optimizing animal health and wellbeing and, ultimately, improving scientific outcomes.

The objective of this review was to examine the available evidence on the experiences and perceptions of nurses working the night shift within any specialty in the acute care, subacute, or long-term care setting.

Nurses are required for around-the-clock patient care. Night shift nurses can experience detrimental effects because of their work hours, which disrupt their normal circadian rhythm. Understanding nurses' experiences and perceptions when working night shift will facilitate the development of strategies to minimize the potential negative effects of working at night. In examining nurses' experiences and perceptions of working night shift, there is scope to explore how to improve night shift nurses' practice environment and job satisfaction, which will then translate to improved nurse and patient outcomes.

This review included qualitative studies focused on the experiences and perceptions of registered nurses and licensed practical nurses who work the night shift or rotate between day and night shift.

This review followed the JBI methodology for systematic reviews of qualitative evidence. The methodology used was consistent with the a priori protocol. Studies included in this review were those published in full text, English, and between 1983 (when the seminal work on hospitals that attract and retain nurses was published) and February 2021, when the search was completed. The main databases searched for published and unpublished studies included MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science.From the search, two reviewers independently screened the studies against the inclusion criteria, and then papers selected for inclusion were assessed for methodological quality. Qualitative data were extracted from the included papers independently by the four reviewers. Results from each reviewer were discussed and clarified to reach agreement. The extracted findings were pooled and examined for shared meaning, coded, and grouped into categories. Common categories were grouped into meta-synthesis to produce a comprehensive set of synthesized findings. The final synthesized findings were graded using the ConQual approach to determine the level of confidence (trust) users may have in the value of the synthesized findings.

Thirty-four papers, representing 33 studies, met the criteria for inclusion. The studies were conducted in 11 countries across six continents, with a total of 601 participants. From these, a total of 220 findings were extracted and combined to form 11 categories based on similarity in meaning, and three syntheses were derived: i) The "Other" Shift: the distinctiveness of night nursing; ii) Juggling sleep and all aspects of life when working nights; and iii) Existing in the Twilight Zone: battling the negative impact of sleep deprivation consumes nurses who strive to keep patients, self, and others safe.

The major conclusions from this review are the uniqueness of working the night shift and the sleep deprivation of night nurses. Organizational strategies and support are needed for those working this shift, which will enhance nurse and patient safety.

PROSPERO CRD42019135294.

A critical unmet medical need in clinical management of colorectal cancer (CRC) pivots around lack of noninvasive and or minimally invasive techniques for early diagnosis and prognostic prediction of clinical outcomes. Because DNA methylation can capture the regulatory landscape of tumors and can be measured in body fluids, it provides unparalleled opportunities for the discovery of early diagnostic and prognostics markers predictive of clinical outcomes. Here we investigated use of DNA methylation for the discovery of potential clinically actionable diagnostic and prognostic markers for predicting survival in CRC.

We analyzed DNA methylation patterns between tumor and control samples to discover signatures of CpG sites and genes associated with CRC and predictive of survival. We conducted functional analysis to identify molecular networks and signaling pathways driving clinical outcomes.

We discovered a signature of aberrantly methylated genes associated with CRC and a signature of thirteen (13) CpG sites predictive of survival. We discovered molecular networks and signaling pathways enriched for CpG sites likely to drive clinical outcomes.

The investigation revealed that CpG sites can predict survival in CRC and that DNA methylation can capture the regulatory state of tumors through aberrantly methylated molecular networks and signaling pathways.