Effects Of Circadian Rhythm Disruption Research Articles

Abstract PO3-25-02: Circadian Rhythm Disruption Accelerates Aggressive Mammary Tumorigenesis by Altering Tumor Microenvironment

Abstract \Breast cancer is the most common cancer in women worldwide, leading to over 650,000 deaths worldwide. The circadian rhythm is a 24-hour biological rhythm that controls most cellular, hormonal, and behavioral processes in living organisms, which is why perturbation of these rhythms is linked to several devastating diseases such as cardiovascular diseases, diabetes, and cancer. In the mammary gland, circadian clocks regulate the rhythmic expression of numerous genes. Circadian rhythm disruption (CRD), which has been termed a "carcinogen" by the International Agency for Research in Cancer, is caused by different factors, one of them being shift work. Several epidemiological studies have revealed that women who work night shifts are predisposed to breast cancer. The aim of this study is to investigate the effect of circadian rhythm disruption on aggressive mammary tumorigenesis. To do this, we used genetically engineered mouse models of mammary tumors (HER2-tumor and triple-negative breast tumor, or TNBC). Chronic jetlag, which mimics shift work in mice and is known to cause CRD, was introduced in one group of mice by perturbing the normal light and dark cycles with an 8-hour advance every three days. Wheel-running, which is represented by an actogram, was used to confirm the circadian disruption in the CRD mice. CRD was found to accelerate tumor initiation with a significant increase in weight in the CRD group of mice. CRD enhanced tumor burden significantly compared to LD mice. Our results also showed high metastatic foci in the lungs of CRD mice compared to LD mice. A flow cytometry study showed a higher cancer stem cell population in CRD tumors. Mammosphere assays with tumor-derived cells showed that CRD increased the number and size of the mammospheres compared to the control tumors. The tumor cells were analyzed using single-cell RNA sequencing, which showed that CRD alters the tumor microenvironment by developing more immunosuppressive and "cold" tumors. The tumor-derived organoids (tumoroid) showed resistance to chemotherapeutics. Finally, bioinformatics analysis using single-cell RNA seq data from human breast tumors (TNBC, ER/PR, and HER2) showed that the malignant cells in TNBC tumors had a significantly higher circadian rhythm disrupted score (CRD score) compared to ER/PR tumors. Taken together, our data showed how circadian rhythm disruption affects TNBC tumorigenesis and drug response by altering the tumor microenvironment. Citation Format: Olajumoke Ogunlusi, Mrinmoy Sarkar, Tristan Nguyen, Devon Boland, James Cai, Arhit Chakrabarti, Bani Mallick, Alex Keene, Tapasree Roy Sarkar. Circadian Rhythm Disruption Accelerates Aggressive Mammary Tumorigenesis by Altering Tumor Microenvironment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-25-02.

Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus

ObjectiveCircadian rhythm disruption (CRD) has been associated with inflammation and immune disorders, but its role in SLE progression is unclear. We aimed to investigate the impact of circadian rhythms on...

Towards personalized burnout prevention system: causal inference approach for understanding the effect of circadian rhythm disruption on well-being

Towards personalized burnout prevention system: causal inference approach for understanding the effect of circadian rhythm disruption on well-being

Integrated Bulk and Single-Cell RNA-Sequencing Reveals the Effects of Circadian Rhythm Disruption on the Metabolic Reprogramming of CD4+ T Cells in Alzheimer's Disease.

Although growing evidence suggests close correlations between Alzheimer's disease (AD) and circadian rhythm disruption (CRD), few studies have focused on the influence of circadian rhythm on levels of immune cells in AD. We aimed to delineate the mechanism underlying the effects of circadian related genes on T cell immune function in AD. A total of 112 brain samples were used to construct the CRD-related model by performing weighted gene co-expression network analysis and machine learning algorithms (LASSO, SVM-RFE, and RF). The ssGSEA method was used to calculate the CRDscore in order to quantify CRD status. Using single-cell transcriptome data of CSF cells, we investigated the CD4+ T cell metabolism and cell-cell communication in high- and low-risk CRD groups. Connectivity map (CMap) was applied to explore small molecule drugs targeting CRD, and the expression of the signature gene GPR4 was furthervalidated in AD. The CRDscore algorithm, which is based on 23 circadian-related genes, can effectively classify the CRD status in AD datasets. The single-cell analysis revealed that the CD4+ T cells with high CRDscore were characterized by hypometabolism. Cell communication analysis revealed that CD4+ T cells might be involved in promoting CD8+ T cell adhesion under CRD, which may facilitate T cell infiltration into the brain parenchyma. Overall, this study indicates the potential connotation of circadian rhythm in AD, providing insights into understanding T cell metabolic reprogramming under CRD.

Circadian Rhythm Perturbation Aggravates Gut Microbiota Dysbiosis in Dextran Sulfate Sodium-Induced Colitis in Mice.

Circadian rhythm disruption is increasingly considered an environmental risk factor for the development and exacerbation of inflammatory bowel disease. We have reported in a previous study that nychthemeral dysregulation is associated with an increase in intestinal barrier permeability and inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. To investigate the effect of circadian rhythm disruption on the composition and diversity of the gut microbiota (GM), sixty male C57BL/6J mice were initially divided to two groups, with the shifted group (n = 30) exposed to circadian shifts for three months and the non-shifted group (n = 30) kept under a normal light-dark cycle. The mice of the shifted group were cyclically housed for five days under the normal 12:12 h light-dark cycle, followed by another five days under a reversed light-dark cycle. At the end of the three months, a colitis was induced by 2% DSS given in the drinking water of 30 mice. Animals were then divided into four groups (n = 15 per group): sham group non-shifted (Sham-NS), sham group shifted (Sham-S), DSS non-shifted (DSS-NS) and DSS shifted (DSS-S). Fecal samples were collected from rectal content to investigate changes in GM composition via DNA extraction, followed by high-throughput sequencing of the bacterial 16S rRNA gene. The mouse GM was dominated by three phyla: Firmicutes, Bacteroidetes and Actinobacteria. The Firmicutes/Bacteroidetes ratio decreased in mice with induced colitis. The richness and diversity of the GM were reduced in the colitis group, especially in the group with inverted circadian rhythm. Moreover, the GM composition was modified in the inverted circadian rhythm group, with an increase in Alloprevotella, Turicibacter, Bacteroides and Streptococcus genera. Circadian rhythm inversion exacerbates GM dysbiosis to a less rich and diversified extent in a DSS-induced colitis model. These findings show possible interplay between circadian rhythm disruption, GM dynamics and colitis pathogenesis.

The Effects Of Circadian Rhythm Disruption On The Inflammatory Response To Particulate Matter Exposure From Woodsmoke

The Effects Of Circadian Rhythm Disruption On The Inflammatory Response To Particulate Matter Exposure From Woodsmoke

Comparing MitoQ10 and heat therapy: Evaluating mechanisms and therapeutic potential for polycystic ovary syndrome induced by circadian rhythm disruption

ABSTRACT Environmental factors, such as sleep restriction, contribute to polycystic ovary syndrome (PCOS) by causing hyperinsulinemia, hyperandrogenism, insulin resistance, and oligo- or anovulation. This study aimed to evaluate the effects of circadian rhythm disruption on reproductive and metabolic functions and investigate the potential therapeutic benefits of MitoQ10 and hot tub therapy (HTT). Sixty female rats were divided into six groups: control, MitoQ10, HTT, and three groups with PCOS induced by continuous light exposure(L/L). The reproductive, endocrine, and structural manifestations ofL/L-induced PCOS were confirmed by serum biochemical measurements, ultrasound evaluation of ovarian size, and vaginal smear examination at week 14. Subsequently, the rats were divided into the L/L (untreated), L/L+MitoQ10-treated, andL/L+HTT-treated groups. At the end of week 22, all rats were sacrificed. Treatmentwith MitoQ10 or HTT partially reversed the reproductive, endocrine, and structural features of PCOS, leading to a decreased amplitude of isolated uterine contractions, ovarian cystic changes and size, and endometrial thickness. Furthermore, both interventions improved the elevated serum levels of anti-Mullerian hormone (AMH), kisspeptin, Fibulin-1, A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS-19), lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), oxidative stress markers, androgen receptors (AR) and their transcription target genes, FKBP52 immunostaining in ovarian tissues, and uterine estrogen receptor alpha (ER-α) and PRimmunostaining. In conclusion, MitoQ10 supplementation and HTT demonstrated the potential for ameliorating metabolic, reproductive, and structural perturbations associated with PCOS induced by circadian rhythm disruption. These findings suggest a potential therapeutic role for these interventions in managing PCOS in women.

Circadian rhythm disruption exacerbates the progression of macrophage dysfunction and alveolar bone loss in periodontitis

Macrophages are highly implicated in the progression of periodontitis, while circadian rhythm disruption (CRD) promotes the inflammatory response of macrophages in many diseases. However, the effects of CRD on periodontitis and the role of macrophages in this process remain unclear. Histone lysinedemethylase6a (Kdm6a), a histone demethylase, has recently been identified as a key regulator of macrophage-induced inflammation. Here, we established an experimental periodontitis model by injecting lipopolysaccharide (LPS) derived from Porphyromonas gingivalis with or without periodontal ligation in mice exposed to an 8-h time shift jet-lag schedule every 3 days. By histomorphometry, tartrate acid phosphatase (TRAP) staining, RT-qPCR, ELISA, immunohistochemistry and immunofluorescence analysis, we found that CRD promoted the inflammatory response, alveolar bone resorption, macrophage infiltration and Kdm6a expression in macrophages. Macrophage-specific Kdm6a knockout mice were further used to elucidate the effects of Kdm6a deficiency on periodontitis. Kdm6a deletion in macrophages rescued periodontal tissue inflammation, osteoclastogenesis, and alveolar bone loss in a mouse model of periodontitis. These findings suggest that CRD may intensify periodontitis by increasing the infiltration and activation of macrophages. Kdm6a promotes the inflammatory response in macrophages, which may participate in aggravated periodontitis via CRD.

Integrative analysis indicates the prognostic value of circadian rhythm disruption in liver cancer: Potential for therapeutic targeting.

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape-for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies.

P-550 Transgenerational epigenetic influences of maternal circadian rhythm changes during pregnancy and lactation periods on cognition and behavior in male offspring

Abstract Study question Do maternal circadian rhythm changes during pregnancy and lactation periods cause transgenerational behavioral and cognitive alterations in male offspring? Summary answer Maternal circadian rhythm changes cause impaired behavioral alterations such as motor activity impairments, increased anxiety and weakening of spatial memory in male offspring. What is known already The circadian system regulates the daily temporal organization in behavior and physiology in most species. Recent publications in model systems have emphasized the negative effects of circadian rhythm disruption on both female and male reproduction and fertility. There is growing concern about the long-term effects of circadian rhythm disruptions during pregnancy and lactation periods on human offspring and their descendants as circadian regulation during these periods can potentially alter epigenetic programing in offspring. However, there is a lack of information about the possible transgenerational effects of circadian rhythm disorders for the health of offspring in the literature. Study design, size, duration Male offspring from pregnant Wistar rats (n = 60) which were exposed to control (12 hours light/12 hours dark), short day (SD) (8 hours light/16 hours dark) or long day (LD) periods (16 hours light/8 hours dark) during only pregnancy, only lactation or both periods (n = 15/group) categorized as control, SD pregnancy (SD-P), SD lactation (SD-L), SD pregnancy and lactation (SD-P+L), LD pregnancy (LD-P), LD lactation (LD-L), LD pregnancy and lactation (LD-P+L) groups. Participants/materials, setting, methods The length of gestation, litter size, sex ratio of pups (fraction male) and birth weights were recorded. The maternal locomotor activity and anxiety were analyzed by open field (OF) and elevated plus maze (EPM) tests, respectively (n = 15 mothers/group). Learning and memory, locomotor activity and anxiety related changes were studied in the male offspring in pre-pubertal, pubertal and adult periods with object localization (OL) and Morris water maze (MWM), OF and EPM tests, respectively. Main results and the role of chance Newborn weights was significantly increased in SD (5.01±0.07) and LD (4.47±0.29) groups compared to control group (3.73±0.03) (p < 0.001). Male sex ratio of pups born to mothers on SD schedule was unusually low (0.21±0.62) compared to mothers on normal light schedule (0.48±0.05) (p < 0.001). The gestation length was not altered. Locomotor activity was increased in mothers exposed to SD schedule (p < 0.01). A significant motor activity impairment in the prepubertal period was remarkable in SD-P+L, LD-P, LD-L and LD-P+L groups (p < 0.001). Compared to control group, EPM test showed that all the offspring in SD groups had significant increase in their anxiety in the prepubertal period. Motor functions that decreased before puberty seems gradually improved at adulthood. Weakened short-term spatial memory was observed at puberty, especially in SD-P (p < 0.001), SD-P+L (p < 0.05), LD-P (p < 0.05) groups. Time to find the platform was significantly higher than those measured for control group for SD-P-L (p < 0.001) in the prepubertal period and LD-P+L group (p < 0.001) in the pubertal period meaning decreased spatial memory and learning. A probe trial given on day 6 with MWM test showed that LD groups had no alterations in spatial memory whereas SD-P (p < 0.05) and SD-G+L (p < 0.001) groups showed impaired changes in long-term spatial memory. Limitations, reasons for caution Due to limitations of working with human subjects exposed to shift work schedules, most chronoregulation research including ours has used rodent models with limitations in translating to human studies. However, to truly know if such concerns apply to humans will require retrospective and prospective human studies. Wider implications of the findings Epigenetic transitions are crucial for transcriptional reprogramming triggered by environmental cues. Our study might provide valuable information regarding transgenerational effects of maternal chronodisruption on health later in life of the offspring, particularly at prepubertal and pubertal periods, create suggestions and guidelines for reproductive biology, shift work and possible infertility problems. Trial registration number This work was supported by research grants from the Scientific and Technological Research Council of Turkey (TUBITAK) (SBAG 219S636) and Akdeniz University, The Scientific Research Projects Coordination Unit (TYL-2018-3580).

Circadian Rhythm Disruption Increases Tumor Growth Rate and Accumulation of Myeloid-Derived Suppressor Cells.

Circadian rhythm disruption is implicated in the initiation and progression of many diseases, including cancer. External stimuli, such as sunlight, serve to synchronize physiological processes and cellular functions to a 24-h cycle. The immune system is controlled by circadian rhythms, and perturbation of these rhythms can potentially alter the immune response to infections and tumors. The effect of circadian rhythm disruption on the immune response to tumors remains unclear. Specifically, the effects of circadian disruption (CD) on immunosuppressive cell types within the tumor, such as myeloid-derived suppressor cells (MDSCs), are unknown. In this study, a shifting lighting schedule is used to disrupt the circadian rhythm of mice. After acclimation to lighting schedules, mice are inoculated with 4T1 or B16-F10 tumors. Tumor growth is increased in mice housed under circadian disrupting lighting conditions compared to standard lighting conditions. Analysis of immune populations within the spleen and tumor shows an increased accumulation of MDSCs within these tissues, suggesting that MDSC mediated immunosuppression plays a role in the enhanced tumor growth caused by circadian disruption. This paves the way for future studies of the effects of CD on immunosuppression in cancer.

Alcohol and Circadian Disruption Minimally Impact Bone Properties in Two Cohorts of Male Mice While Between-Cohort Differences Predominate: Association With Season of Birth?

ABSTRACTMany lifestyle factors affect bone. Sleep deprivation increases risk for fractures and alcohol consumption can lead to alterations in the skeleton. How combined exposure to these two risk factors affects bone is unclear. Thus, we sought to determine the effects of circadian rhythm disruption and chronic alcohol intake on bone structure and mechanical properties in mice. A total of 120 male C57BL/6J mice were used in two cohorts of 60 mice each because of limited availability of light‐tight housing cabinets. One cohort was born in winter and the other in summer. Mice were randomly assigned to circadian disruption (weekly shifting of the light/dark cycle) and control (no shifting) groups beginning at 8 to 12 weeks of age for 12 weeks at which time mice were administered an alcohol‐containing or control diet for an additional 10 weeks. Bone structure and mechanical properties of the femur were assessed by micro‐computed tomography and three‐point bending, respectively. The initial data analysis revealed a likely cohort effect. Thus, we used a three‐way analysis of variance to assess the effects of circadian rhythm disruption, alcohol intake, and cohort. Circadian rhythm disruption alone had minimal effects on bone structure and mechanical properties. Alcohol intake reduced body mass and had minimal effects on cortical bone regardless of circadian disruption. Alcohol intake resulted in higher trabecular bone volume, but these beneficial effects were blunted when circadian rhythm was disrupted. Cohort significantly affected body size, many cortical bone structure outcomes, some trabecular bone structure outcomes, and tissue‐level material properties. Thus, cohort had the predominant effect on bone structure and mechanical properties in this study, with chronic alcohol intake and environmental circadian disruption having less consistent effects. The data indicate that season of birth may affect skeletal phenotypes and that studies requiring multiple cohorts should determine if a cohort effect exists. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Night shift work and the risk of metabolic syndrome: Findings from an 8-year hospital cohort.

ObjectivesStudies concerning the risk of metabolic syndrome associated with night work have shown inconsistent findings, due to imprecise working time data and cross-sectional design. We used register-based daily working time data to examine the risk of incident metabolic syndrome associated with night shift work.MethodsWorking time data collected between 2010 and 2018 of 5775 Taiwanese hospital workers were used to identify night shift workers and to calculate the number of night shifts. Metabolic syndrome was identified by annual occupational health examination results, which were linked to the working time data. Logistic regression models and generalized estimating equations were used to examine the association between night shift work and metabolic syndrome and the 5 components of metabolic syndrome.ResultsNight shift work is associated with a higher risk of developing metabolic syndrome (adjusted OR = 1.36, 95% CI = 1.04 to 1.78) and high waist circumference (adjusted OR = 1.27, 95% CI = 1.07 to 1.78) compared to day work. Among night shift workers, increased number of night shifts was associated with high blood pressure (adjusted OR = 1.15, 95% CI = 1.01 to 1.31).ConclusionsNight shift work is associated with metabolic risk factors. Long-term effects of circadian rhythm disruption on metabolic disturbances needs to be further studied.

Circadian Rhythm Disruption Influenced Hepatic Lipid Metabolism, Gut Microbiota and Promoted Cholesterol Gallstone Formation in Mice.

BackgroundHepatic lipid metabolism regulates biliary composition and influences the formation of cholesterol gallstones. The genes Hmgcr and Cyp7a1, which encode key liver enzymes, are regulated by circadian rhythm-related transcription factors. We aimed to investigate the effect of circadian rhythm disruption on hepatic cholesterol and bile acid metabolism and the incidence of cholesterol stone formation.MethodsAdult male C57BL/6J mice were fed either a lithogenic diet (LD) only during the sleep phase (time-restricted lithogenic diet feeding, TRF) or an LD ad libitum (non-time-restricted lithogenic diet feeding, nTRF) for 4 weeks. Food consumption, body mass gain, and the incidence of gallstones were assessed. Circulating metabolic parameters, lipid accumulation in the liver, the circadian expression of hepatic clock and metabolic genes, and the gut microbiota were analyzed.ResultsTRF caused a dysregulation of the circadian rhythm in the mice, characterized by significant differences in the circadian expression patterns of clock-related genes. In TRF mice, the circadian rhythms in the expression of genes involved in bile acid and cholesterol metabolism were disrupted, as was the circadian rhythm of the gut microbiota. These changes were associated with high biliary cholesterol content, which promoted gallstone formation in the TRF mice.ConclusionDisordered circadian rhythm is associated with abnormal hepatic bile acid and cholesterol metabolism in mice, which promotes gallstone formation.

Circadian rhythm disruption with high-fat diet impairs glycemic control and bone quality.

Biological functions, including glycemic control and bone metabolism, are highly influenced by the body's internal clock. Circadian rhythms are biological rhythms that run with a period close to 24hours and receive input from environmental stimuli, such as the light/dark cycle. We investigated the effects of circadian rhythm disruption (CRD), through alteration of the light/dark schedule, on glycemic control and bone quality of mice. Ten-week-old male mice (C57/BL6, n=48) were given a low-fat diet (LFD) or a high-fat diet (HFD) and kept on a dayshift or altered schedule (RSS3) for 22weeks. Mice were divided into four experimental groups (n=12/group): Dayshift/LFD, Dayshift/HFD, RSS3/LFD, and RSS3/HFD. CRD in growing mice fed a HFD resulted in a diabetic state, with a 36.2% increase in fasting glucose levels compared to the Dayshift/LFD group. Micro-CT scans of femora revealed a reduction in inner and outer surface expansion for mice on a HFD and altered light schedule. Cancellous bone demonstrated deterioration of bone quality as trabecular number and thickness decreased while trabecular separation increased. While HFD increased cortical bone mineral density, its combination with CRD reduced this phenomenon. The growth of mineral crystals, determined by small angle X-ray scattering, showed HFD led to smaller crystals. Considering modifications of the organic matrix, regardless of diet, CRD exacerbated the accumulation of fluorescent advanced glycation end-products (fAGEs) in collagen. Strength testing of tibiae showed that CRD mitigated the higher strength in the HFD group and increased brittleness indicated by lower post-yield deflection and work-to-fracture. Consistent with accumulation of fAGEs, various measures of toughness were lowered with CRD, but combination of CRD with HFD protected against this decrease. Differences between strength and toughness results represent different contributions of structural and material properties of bone to energy dissipation. Collectively, these results demonstrate that combination of CRD with HFD impairs glycemic control and have complex effects on bone quality.

O-158 The effect of circadian rhythm disruption due to constant light on ovarian and oocyte aging through possible relationship between PER2 and mTOR signaling pathway

Abstract Study question Does circadian rhythm disruption by constant light affect the ovarian morphology and function, and cause ovarian and oocyte aging through possible relationship between PER2 and mTOR? Summary answer We demonstrated that circadian rhythm disruption by light may cause ovarian and oocyte aging. What is known already Circadian rhythm regulates multiple physiological processes and PER2 is one of the core circadian rhythm components. Changes in light conditions may cause circadian rhythm disruptions. Light exposure at night may cause attenuation in PER2 mRNA and protein levels. Circadian rhythm disruptions are thought to be associated with reproductive diseases. mTOR signaling pathway functions in folliculogenesis and oocyte maturation in ovary. Also, it is associated with ovarian and oocyte aging. Study design, size, duration A total of 32 female Balb/c mice which enter estrous cycle were used in the study. Mice were randomly assigned to one of two groups as 12:12h L:D and 12:12h L:L. During the experiment, 12:12h L:D (control group) was housed in a 12:12h light:dark cycle and 12:12h L:L (experiment group) was housed in a constant light conditions 12:12h light:light for 1 week. Participants/materials, setting, methods We housed 12:12h L:D group in standard lightening conditions and 12:12h L:L group in constant light for one week. We performed food intake and body weight change analysis. We evaluated ovarian morphology, follicle counting analysis. We evaluated ZP3 and nitrotyrosine (NTY) expression for oocyte aging markers. We performed western blot for PER2, mTOR, p-mTOR, p70 S6K, p-p70 S6K, and Caspase-3 protein levels. Main results and the role of chance We demonstrated that circadian rhythm disruption caused alteration in their food intake and decrease in primordial follicle numbers and increase in atretic follicles (p < 0.05). It caused increase in oxidative stress and decrease in ZP3 expression in oocytes (p < 0.05). We showed decreased protein levels of PER2, mTOR, p-mTOR and p70 S6K (p < 0.05). Limitations, reasons for caution The explanation of molecular mechanism underlying the relationship between circadian rhythm disruptions by light and ovarian function may lead the usage of circadian rhythm-based or light-based therapies currently using to treat some diseases on female reproductive system related diseases. Wider implications of the findings We conclude that constant light may reduce follicle reserve, cause follicles to go rapidly atresia and disrupt the oocyte quality, thus it may be a risk factor for female reproductive diseases such as premature ovarian insufficiency and early menopause. Trial registration number not applicable

Chronic shift-lag promotes NK cell ageing and impairs immunosurveillance in mice by decreasing the expression of CD122.

Long‐term subjection to shift work increases the risk of cancer. The purpose of the present study was to explore the mechanism by which chronic circadian disruption impairs natural killer (NK) cell immunosurveillance. Mice were subjected to light‐dark reverse every 4 days for 12 weeks to disrupt normal circadian rhythm. NK cell development and function were evaluated by flow cytometry. The mRNA and protein levels of period 1 (per1) and per2 were suppressed, while circadian locomotor output cycle kaput (CLOCK) was increased in the shifted mice, indicating successful generation of the circadian rhythm disruption mouse model. Chronic shift‐lag promoted NK cell ageing, which is likely due to the reduction in Ly49 family receptor expression in shifted NK. We further studied the effects of circadian rhythm disruption on NK cell function. Chronic shift‐lag inhibited NK cell secretion of granular CD107a and interferon gamma. Moreover, chronic shift‐lag attenuated the clearance of MHC‐I–deficient tumour cells by NK cells in vivo and promoted lung metastasis of B16F10 melanomas. Furthermore, chronic shift‐lag reduced NK cell killing function, which may be due to the suppression of Eomes transcription factor expression, which inhibiting the transcription of CD122. In conclusion, our findings suggest that chronic circadian disruption attenuates NK cell cytolytic activity by decreasing the expression of CD122.

Chronodisruption: effects on reproduction, transgenerational health of offspring and epigenome.

The circadian system regulates the daily temporal organization in behavior and physiology, including neuroendocrine rhythms and reproduction. Modern life, however, increasingly impacts this complex biological system. Due to limitations of working with human subjects exposed to shift work schedules, most chronoregulation research has used rodent models. Recent publications in these model systems have emphasized the negative effects of circadian rhythm disruption on both female and male reproductive systems and fertility. Additionally, there is growing concern about the long-term effects of circadian rhythm disruptions during pregnancy on human offspring and their descendants as circadian regulation during pregnancy can also alter epigenetic programing in offspring. However, to truly know if such concerns apply to humans will require retrospective and prospective human studies. Therefore, this review will highlight the latest available evidence regarding potential effects of chronodisruption on both female and male reproductive systems. Additionally, it presents a comprehensive summary of transgenerational and epigenetic effects on adult offspring that result from maternal chronodisruption.

The Effects of Circadian Rhythm Disruption on Mental Health and Physiological Responses among Shift Workers and General Population.

Background: The effect of circadian disruption on the bio-psychological clock system has been widely studied. However, the mechanism and the association of circadian rhythm disruption with mental health and physiological responses are still unclear. Therefore, this study was conducted to investigate the effects of circadian rhythm disruption on mental health and physiological responses among shift workers and the general population. Methods: A total of 42 subjects participated in this quasi-experimental study. Participants were divided into a group of shift workers (n = 20) and a general population group (n = 22). Polysomnography tests, blood tests (cortisol, triglycerides and glucose), and psychological tests (Abbreviated Profile of Mood States, General Health Questionnaire-28, Working Memory and Processing Speed Indexes of the Wechsler Adult Intelligent Scale (WAIS-IV) were used to examine the effects of circadian rhythm disruption. Results: The results showed a significant relationship between circadian rhythm disruption and mood (r = 0.305, p < 0.05). The findings of this study also indicated that there was a significant effect of circadian rhythm disruption on mood (F(2,40) = 8.89, p < 0.001, η2 =0.182), processing speed (F(2,40) = 9.17, p < 0.001, η2 = 0.186) and working memory (F(2,40) = 4.963, p < 0.01, η2 = 0.11) in shift workers and the general population. Conclusions: Our findings showed that circadian rhythm disruption affects mood and cognitive performance, but it does not significantly affect psychological wellbeing and physiological responses. Future studies are warranted to examine moderator and mediator variables that could influence the circadian rhythm disruption.

Pengaruh Perubahan Ritme Sirkadian terhadap Marker Inflamasi pada Pedagang Pasar Subuh di Kota Palangka Raya

Dawn market traders in Pasar Seram Palangka Raya City with sleep deprivation and alteration of sleep pattern has the potential risk of circadian rhythm disruption. Circadian rhythm disruption is the beginning of various chronic diseases such as coronary heart disease. One of the inflammation markers that can be used to assess the onset of atherosclerosis and coronary heart disease is the platelet profile (platelet count, mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT)). This study aimed to describe the effect of circadian rhythm disruption of inflammation marker as a platelet profile in dawn market traders in Pasar Seram Palangka Raya City. The descriptive observational method with a cross-sectional design was used in this study. Samples obtained as many as 100 people using purposive sampling technique. The examination of the platelet profile was done by an automated method using a hematology analyzer. The results showed, there was 6% with high platelet count and it only in women. Whereas for platelet indices in men, there was 6% with high MPV, 74% with high PCT, and 10% with low PCT. In women, there was 84% with high PCT and 6% with low PCT (6%). The result showed there were inflammation and accumulation of platelets as a result of circadian rhythm disruption in dawn market traders.