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1.
Cell Rep Methods ; 3(2): 100397, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36936083

RESUMO

The temporal organization of biological systems is key for understanding them, but current methods for identifying this organization are often ad hoc and require prior knowledge. We present Phasik, a method that automatically identifies this multiscale organization by combining time series data (protein or gene expression) and interaction data (protein-protein interaction network). Phasik builds a (partially) temporal network and uses clustering to infer temporal phases. We demonstrate the method's effectiveness by recovering well-known phases and sub-phases of the cell cycle of budding yeast and phase arrests of mutants. We also show its general applicability using temporal gene expression data from circadian rhythms in wild-type and mutant mouse models. We systematically test Phasik's robustness and investigate the effect of having only partial temporal information. As time-resolved, multiomics datasets become more common, this method will allow the study of temporal regulation in lesser-known biological contexts, such as development, metabolism, and disease.

2.
Front Nutr ; 10: 1143001, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937362

RESUMO

The circadian clock governs activity of many physiological processes, thereby playing a pivotal role in human health. Circadian disruption is closely associated with cancer development; in particular, recent discoveries have provided strong evidence supporting specific functions of different molecular clock components in either promoting or inhibiting tumorigenesis. This narrative review aims to summarize the existing data on molecular connections between the clock and cancer. These results along with future efforts pave the road to targeting the circadian clock as a novel pathway for therapeutic intervention. Given the implications of chrono-nutrition interventions such as time-restricted feeding in extending lifespan, chrono-nutrition may have preventive and therapeutic applications for individuals with and at-risk of age-related diseases including cancer.

3.
Curr Neuropharmacol ; 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36918783

RESUMO

The synthesis and release of melatonin in the brain harmonize various physiological functions. The apparent decline in melatonin levels with advanced aging is an aperture to the neurodegenerative processes. It has been indicated that down regulation of melatonin leads to alterations of circadian rhythm components, which further causes a desynchronization of several genes and results in an increased susceptibility to develop neurodegenerative diseases. Additionally, as circadian rhythms and memory are intertwined, such rhythmic disturbances influence memory formation and recall. Besides, cell cycle events exhibit a remarkable oscillatory system, which is downstream of the circadian phenomena. The linkage between the molecular machinery of the cell cycle and complex fundamental regulatory proteins emphasizes the conjectural regulatory role of cell cycle components in neurodegenerative disorders such as Alzheimer's disease. Among the mechanisms intervening long before the signs of the disease appear, the disturbances of the circadian cycle, as well as the alteration of the machinery of the cell cycle and impaired neurogenesis, must hold our interest. Therefore, in the present review, we propose to discuss the underlying mechanisms of action of melatonin in regulating the circadian rhythm, cell cycle components and adult neurogenesis in the context of AD pathogenesis with the view that it might further assist to identify new therapeutic targets.

4.
Nutr Rev ; 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36940184

RESUMO

The imbalance between energy intake and expenditure in an environment of continuous food availability can lead to metabolic disturbances in the body and increase the risk of obesity and a range of chronic noncommunicable diseases. Intermittent fasting (IF) is one of the most popular nonpharmacological interventions to combat obesity and chronic noncommunicable diseases. The 3 most widely studied IF regimens are alternate-day fasting, time-restricted feeding, and the 5:2 diet. In rodents, IF helps optimize energy metabolism, prevent obesity, promote brain health, improve immune and reproductive function, and delay aging. In humans, IF's benefits are relevant for the aging global population and for increasing human life expectancy. However, the optimal model of IF remains unclear. In this review, the possible mechanisms of IF are summarized and its possible drawbacks are discussed on the basis of the results of existing research, which provide a new idea for nonpharmaceutical dietary intervention of chronic noncommunicable diseases.

5.
J Transl Med ; 21(1): 185, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36895015

RESUMO

BACKGROUND: Circadian rhythm regulates complex physiological activities in organisms. A strong link between circadian dysfunction and cancer has been identified. However, the factors of dysregulation and functional significance of circadian rhythm genes in cancer have received little attention. METHODS: In 18 cancer types from The Cancer Genome Atlas (TCGA), the differential expression and genetic variation of 48 circadian rhythm genes (CRGs) were examined. The circadian rhythm score (CRS) model was created using the ssGSEA method, and patients were divided into high and low groups based on the CRS. The Kaplan-Meier curve was created to assess the patient survival rate. Cibersort and estimate methods were used to identify the infiltration characteristics of immune cells between different CRS subgroups. Gene Expression Omnibus (GEO) dataset is used as verification queue and model stability evaluation queue. The CRS model's ability to predict chemotherapy and immunotherapy was assessed. Wilcoxon rank-sum test was used to compare the differences of CRS among different patients. We use CRS to identify potential "clock-drugs" by the connective map method. RESULTS: Transcriptomic and genomic analyses of 48 CRGs revealed that most core clock genes are up-regulated, while clock control genes are down-regulated. Furthermore, we show that copy number variation may affect CRGs aberrations. Based on CRS, patients can be classified into two groups with significant differences in survival and immune cell infiltration. Further studies showed that patients with low CRS were more sensitive to chemotherapy and immunotherapy. Additionally, we identified 10 compounds (e.g. flubendazole, MLN-4924, ingenol) that are positively associated with CRS, and have the potential to modulate circadian rhythms. CONCLUSIONS: CRS can be utilized as a clinical indicator to predict patient prognosis and responsiveness to therapy, and identify potential "clock-drugs".


Assuntos
Relógios Circadianos , Neoplasias , Humanos , Relógios Circadianos/genética , Variações do Número de Cópias de DNA , Ritmo Circadiano/genética , Neoplasias/genética , Prognóstico
6.
Sleep ; 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36881684

RESUMO

This White Paper addresses the current gaps in knowledge, as well as opportunities for future studies in pediatric sleep. The Sleep Research Society's Pipeline Development Committee assembled a panel of experts tasked to provide information to those interested in learning more about the field of pediatric sleep, including trainees. We cover the scope of pediatric sleep, including epidemiological studies and the development of sleep and circadian rhythms in early childhood and adolescence. Additionally, we discuss current knowledge of insufficient sleep and circadian disruption, addressing the neuropsychological impact (affective functioning) and cardiometabolic consequences. A significant portion of this White Paper explores pediatric sleep disorders (including circadian rhythm disorders, insomnia, restless leg and periodic limb movement disorder, narcolepsy, and sleep apnea), as well as sleep and neurodevelopment disorders (e.g., autism and attention deficit hyperactivity disorder). Finally, we end with a discussion on sleep and public health policy. Although we have made strides in our knowledge of pediatric sleep, it is imperative that we address the gaps in our knowledge and the pitfalls of our methodologies. For example, more work needs to be done to assess pediatric sleep using objective methodologies (i.e., actigraphy and polysomnography), to explore sleep disparities, to improve accessibility to evidence-based treatments, and to identify potential risks and protective markers of disorders in children. Expanding trainee exposure to pediatric sleep and elucidating future directions for study will significantly improve the future of the field.

7.
Hypertension ; 80(4): 861-871, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36876501

RESUMO

BACKGROUND: Although insufficient sleep has been shown to contribute to obesity-related elevated blood pressure, the circadian timing of sleep has emerged as a novel risk factor. We hypothesized that deviations in sleep midpoint, a measure of circadian timing of sleep, modify the association between visceral adiposity and elevated blood pressure in adolescents. METHODS: We studied 303 subjects from the Penn State Child Cohort (16.2±2.2 years; 47.5% female; 21.5% racial/ethnic minority). Actigraphy-measured sleep duration, midpoint, variability, and regularity were calculated across a 7-night period. Visceral adipose tissue (VAT) was measured with dual-energy X-ray absorptiometry. Systolic blood pressure (SBP) and diastolic blood pressure levels were measured in the seated position. Multivariable linear regression models tested sleep midpoint and its regularity as effect modifiers of VAT on SBP/diastolic blood pressure levels, while adjusting for demographic and sleep covariables. These associations were also examined as a function of being in-school or on-break. RESULTS: Significant interactions were found between VAT and sleep irregularity, but not sleep midpoint, on SBP (P interaction=0.007) and diastolic blood pressure (P interaction=0.022). Additionally, significant interactions were found between VAT and schooldays sleep midpoint on SBP (P interaction=0.026) and diastolic blood pressure (P interaction=0.043), whereas significant interactions were found between VAT and on-break weekdays sleep irregularity on SBP (P interaction=0.034). CONCLUSIONS: A delayed and an irregular sleep midpoint during school and during free-days, respectively, increase the impact of VAT on elevated blood pressure in adolescents. These data suggest that deviations in the circadian timing of sleep contribute to the increased cardiovascular sequelae associated with obesity and that its distinct metrics require measurement under different entrainment conditions in adolescents.


Assuntos
Ritmo Circadiano , Hipertensão , Criança , Humanos , Feminino , Adolescente , Masculino , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Adiposidade , Etnicidade , Grupos Minoritários , Obesidade
8.
Semin Cancer Biol ; 91: 99-109, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36893964

RESUMO

The circadian rhythm is regulated by an intrinsic time-tracking system, composed both of a central and a peripheral clock, which influences the cycles of activities and sleep of an individual over 24 h. At the molecular level, the circadian rhythm begins when two basic helix-loop-helix/Per-ARNT-SIM (bHLH-PAS) proteins, BMAL-1 and CLOCK, interact with each other to produce BMAL-1/CLOCK heterodimers in the cytoplasm. The BMAL-1/CLOCK target genes encode for the repressor components of the clock, cryptochrome (Cry1 and Cry2) and the Period proteins (Per1, Per2 and Per3). It has been recently demonstrated that the disruption of circadian rhythm is associated with an increased risk of developing obesity and obesity-related diseases. In addition, it has been demonstrated that the disruption of the circadian rhythm plays a key role in tumorigenesis. Further, an association between the circadian rhythm disruptions and an increased incidence and progression of several types of cancer (e.g., breast, prostate, colorectal and thyroid cancer) has been found. As the perturbation of circadian rhythm has adverse metabolic consequences (e.g., obesity) and at the same time tumor promoter functions, this manuscript has the aim to report how the aberrant circadian rhythms affect the development and prognosis of different types of obesity-related cancers (breast, prostate, colon rectal and thyroid cancer) focusing on both human studies and on molecular aspects.

9.
Poult Sci ; 102(5): 102548, 2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36907128

RESUMO

Various aspects of activity, such as spontaneous activity, explorative activity, activity in open-field tests, and hyperactivity syndrome have been explored as causal factors of feather pecking in laying hens, with no clear results. In all previous studies, mean values of activity over different time intervals were used as criteria. Incidental observation of alternated oviposition time in lines selected for high (HFP) and low feather pecking (LFP), supported by a recent study which showed differentially expressed genes related to the circadian clock in the same lines, led to the hypothesis that feather pecking may be related to a disturbed diurnal activity rhythm. Hence activity recordings of a previous generation of these lines have been reanalyzed. Data sets of a total of 682 pullets of 3 subsequent hatches of HFP, LFP, and an unselected control line (CONTR) were used. Locomotor activity was recorded in pullets housed in groups of mixed lines in a deep litter pen on 7 consecutive 13-h light phases, using a radio-frequency identification antenna system. The number of approaches to the antenna system was recorded as a measure of locomotor activity and analyzed using a generalized linear mixed model including hatch, line, time of day and the interactions of hatch × time of day and line × time of day as fixed effects. Significant effects were found for time and the interaction line × time of day but not for line. All lines showed a bimodal pattern of diurnal activity. The peak activity of the HFP in the morning was lower than that of the LFP and CONTR. In the afternoon peak all lines differed with the highest mean in the LFP followed by CONTR and HFP. The present results provide support for the hypothesis that a disturbed circadian clock plays a role in the development of feather pecking.

10.
Anal Chim Acta ; 1251: 340971, 2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-36925277

RESUMO

Circadian desynchrony with the external light-dark cycle influences the rhythmic secretion of melatonin which is among the first signs of circadian rhythm sleep disorders. An accurate dim light melatonin onset (established indicator of circadian rhythm sleep disorders) measurement requires lengthy assays, and antibody affinities alterations, especially in patients with circadian rhythm disorders whose melatonin salivary levels vary significantly, making antibodies detection mostly inadequate. In contrast, aptamers with their numerous advantages (e.g., target selectivity, structural flexibility in tuning binding affinities, small size, etc.) can become preferable biorecognition molecules for salivary melatonin detection with high sensitivity and specificity. This study thoroughly characterizes the structural property and binding mechanism of a single-stranded DNA aptamer full sequence (MLT-C-1) and its truncated versions (MLT-A-2, MLT-A-4) to decipher its optimal characteristics for saliva melatonin detection. We use circular dichroism spectroscopy to determine aptamers' conformational changes under different ionic strengths and showed that aptamers display a hairpin loop structure where few base pairs in the stem play a significant role in melatonin binding and formation of aptamer stabilized structure. Through microscale thermophoresis, aptamers demonstrated a high binding affinity in saliva samples (MLT-C-1F Kd = 12.5 ± 1.7 nM; MLT-A-4F Kd = 11.2 ± 1.6 nM; MLT-A-2F Kd = 2.4 ± 2.8 nM; limit-of-detection achieved in pM, highest sensitivity attained for MLT-A-2F aptamer with the lowest detection limit of 1.35 pM). Our data suggest that aptamers are promising as biorecognition molecules and provide the baseline parameters for the development of an aptamer-based point-of-care diagnostic system for melatonin detection and accurate profiling of its fluctuations in saliva.


Assuntos
Aptâmeros de Nucleotídeos , Relógios Circadianos , Melatonina , Transtornos do Sono do Ritmo Circadiano , Transtornos do Sono-Vigília , Humanos , Transtornos do Sono do Ritmo Circadiano/diagnóstico , Ritmo Circadiano , Aptâmeros de Nucleotídeos/análise , Saliva/química
11.
Nutrition ; 110: 112008, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36940625

RESUMO

OBJECTIVES: This study aimed to evaluate the association of vitamin D with sleep quality during the COVID-19 pandemic and the influence of daily sunlight on this association. METHODS: This cross-sectional, population-based study among adults stratified by multistage probability cluster sampling was conducted from October to December 2020 in the Iron Quadrangle region of Brazil. The outcome was sleep quality, evaluated by the Pittsburgh Sleep Quality Index. Vitamin D (25-hydroxyvitamin D) concentrations were determined by indirect electrochemiluminescence and a deficiency was classified as 25(OH)D < 20 ng/mL. To assess sunlight, the average daily sunlight exposure was calculated and was classified as insufficient when less than 30 min/d. Multivariate logistic analysis was used to estimate the association between vitamin D and sleep quality. A directed acyclic graph was used to select minimal and sufficient sets of adjustment variables for confounding from the backdoor criterion. RESULTS: In a total of 1709 individuals evaluated, the prevalence of vitamin D deficiency was 19.8% (95% CI, 15.5-24.9%), and the prevalence of poor sleep quality was 52.5% (95% CI, 48.6-56.4%). In multivariate analysis, vitamin D was not associated with poor sleep quality in individuals with sufficient sunlight. Moreover, in individuals with insufficient sunlight, vitamin D deficiency was associated with poor sleep quality (odds ratio [OR], 2.02; 95% CI, 1.10-3.71). Furthermore, each 1-ng/mL increase in vitamin D levels reduced the chance of poor sleep quality by 4.2% (OR, 0.96; 95% CI, 0.92-0.99). CONCLUSIONS: Vitamin D deficiency was associated with poor sleep quality in individuals with insufficient exposure to sunlight.

12.
Free Radic Biol Med ; 200: 26-35, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36893944

RESUMO

Nicotine has shown the toxic effects on male reproductive system, and testicular damage is associated with ferroptosis, which is a non-apoptotic regulated cell death driven by iron-dependent lipid peroxidation. However, the role of nicotine on ferroptosis of testicular cells is largely elusive. In the present study, we showed that nicotine destroyed blood-testis barrier (BTB) by interfering with the circadian rhythm of BTB-related factors (ZO-1, N-Cad, Occludin and CX-43) and induced ferroptosis, as reflected via increased clock-control levels of lipid peroxide and decreased ferritin and GPX4, which involved in the circadian. Inhibition of ferroptosis with Fer-1 alleviated nicotine-induced injury of BTB and impaired sperm in vivo. Mechanically, we uncover that the core molecular clock protein, Bmal1, regulates the expression of Nrf2 via direct E-box binding to its promoter to regulate its activity, and nicotine decreases the transcription of Nrf2 through Bmal1 and inactivates Nrf2 pathway and its downstream antioxidant gene, which leads to the imbalance of redox state and ROS accumulation. Intriguingly, nicotine induced lipid peroxidation and subsequent ferroptosis by Bmal1-mediated Nrf2. In conclusion, our study reveals a clear role for the molecular clock in controlling Nrf2 in testis to mediate the ferroptosis induced by nicotine. These findings provide a potential mechanism to prevent smoking and/or cigarette smoke-induced male reproductive injury.

13.
Nutrients ; 15(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36904241

RESUMO

Childhood obesity increases the risk of developing metabolic syndrome later in life. Moreover, metabolic dysfunction may be inherited into the following generation through non-genomic mechanisms, with epigenetics as a plausible candidate. The pathways involved in the development of metabolic dysfunction across generations in the context of childhood obesity remain largely unexplored. We have developed a mouse model of early adiposity by reducing litter size at birth (small litter group, SL: 4 pups/dam; control group, C: 8 pups/dam). Mice raised in small litters (SL) developed obesity, insulin resistance and hepatic steatosis with aging. Strikingly, the offspring of SL males (SL-F1) also developed hepatic steatosis. Paternal transmission of an environmentally induced phenotype strongly suggests epigenetic inheritance. We analyzed the hepatic transcriptome in C-F1 and SL-F1 mice to identify pathways involved in the development of hepatic steatosis. We found that the circadian rhythm and lipid metabolic process were the ontologies with highest significance in the liver of SL-F1 mice. We explored whether DNA methylation and small non-coding RNAs might be involved in mediating intergenerational effects. Sperm DNA methylation was largely altered in SL mice. However, these changes did not correlate with the hepatic transcriptome. Next, we analyzed small non-coding RNA content in the testes of mice from the parental generation. Two miRNAs (miR-457 and miR-201) appeared differentially expressed in the testes of SL-F0 mice. They are known to be expressed in mature spermatozoa, but not in oocytes nor early embryos, and they may regulate the transcription of lipogenic genes, but not clock genes, in hepatocytes. Hence, they are strong candidates to mediate the inheritance of adult hepatic steatosis in our murine model. In conclusion, litter size reduction leads to intergenerational effects through non-genomic mechanisms. In our model, DNA methylation does not seem to play a role on the circadian rhythm nor lipid genes. However, at least two paternal miRNAs might influence the expression of a few lipid-related genes in the first-generation offspring, F1.


Assuntos
Fígado Gorduroso , MicroRNAs , Obesidade Pediátrica , Masculino , Camundongos , Animais , Modelos Animais de Doenças , Sêmen , Epigênese Genética , Metilação de DNA , Lipídeos
14.
Nutrients ; 15(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36904255

RESUMO

Global epidemiologic evidence supports an interrelationship between sleep disorders and fruits and vegetable ingestion. Polyphenols, a broad group of plant substances, are associated with several biologic processes, including oxidative stress and signaling pathways that regulate the expression of genes promoting an anti-inflammatory environment. Understanding whether and how polyphenol intake is related to sleep may provide avenues to improve sleep and contribute to delaying or preventing the development of chronic disease. This review aims to assess the public health implications of the association between polyphenol intake and sleep and to inform future research. The effects of polyphenol intake, including chlorogenic acid, resveratrol, rosmarinic acid, and catechins, on sleep quality and quantity are discussed to identify polyphenol molecules that may improve sleep. Although some animal studies have investigated the mechanisms underlying the effects of polyphenols on sleep, the paucity of trials, especially randomized controlled trials, does not allow for conducting a meta-analysis to reach clear conclusions about the relationships among these studies to support the sleep-improving effects of polyphenols.


Assuntos
Polifenóis , Sono , Animais , Humanos , Polifenóis/farmacologia , Resveratrol , Frutas/química , Verduras
15.
J Hazard Mater ; 448: 130959, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36860044

RESUMO

As alternatives to perfluorooctane sulfonate (PFOS), 6:2 Cl-PFESA (F-53B) and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) are frequently detected in aquatic environments, but little is known about their neurotoxicity, especially in terms of circadian rhythms. In this study, adult zebrafish were chronically exposed to 1 µM PFOS, F-53B and OBS for 21 days taking circadian rhythm-dopamine (DA) regulatory network as an entry point to comparatively investigate their neurotoxicity and underlying mechanisms. The results showed that PFOS may affect the response to heat rather than circadian rhythms by reducing DA secretion due to disruption of calcium signaling pathway transduction caused by midbrain swelling. In contrast, F-53B and OBS altered the circadian rhythms of adult zebrafish, but their mechanisms of action were different. Specifically, F-53B might alter circadian rhythms by interfering with amino acid neurotransmitter metabolism and disrupting blood-brain barrier (BBB) formation, whereas OBS mainly inhibited canonical Wnt signaling transduction by reducing cilia formation in ependymal cells and induced midbrain ventriculomegaly, finally triggering imbalance in DA secretion and circadian rhythm changes. Our study highlights the need to focus on the environmental exposure risks of PFOS alternatives and the sequential and interactive mechanisms of their multiple toxicities.


Assuntos
Ácidos Alcanossulfônicos , Peixe-Zebra , Animais , Ritmo Circadiano
16.
Sci Total Environ ; : 162934, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36934930

RESUMO

Results of human and animal studies independently suggest that either ambient fine particulate matter (PM2.5) air pollution exposure or a disturbed circadian rhythm (circadian dyssynchrony) are important contributing factors to the rapidly evolving type-2-diabetes (T2D) epidemic. The objective of this study is to investigate whether circadian dyssynchrony increases the susceptibility to PM2.5 and how PM2.5 affects metabolic health in circadian dyssynchrony. We examined systemic and organ-specific changes in glucose homeostasis and insulin sensitivity in mice maintained on a regular (12/12 h light/dark) or disrupted (18/6 h light/dark, light-induced circadian dyssynchrony, LICD) light cycle exposed to air or concentrated PM2.5 (CAP, 6 h/day, 30 days). Exposures during Zeitgeber ZT3-9 or ZT11-17 (Zeitgeber in circadian time, ZT0 = begin of light cycle) tested for time-of-day PM2.5 sensitivity (chronotoxicity). Mice transgenic for lung-specific overexpression of extracellular superoxide dismutase (ecSOD-Tg) were used to assess the contribution of CAP-induced pulmonary oxidative stress. Both, CAP exposure from ZT3-9 or ZT11-17, decreased glucose tolerance and insulin sensitivity in male mice with LICD, but not in female mice or in mice kept on a regular light cycle. Although changes in glucose homeostasis in CAP-exposed male mice with LICD were not associated with obesity, they were accompanied by white adipose tissue (WAT) inflammation, impaired insulin signaling in skeletal muscle and liver, and systemic and pulmonary oxidative stress. Preventing CAP-induced oxidative stress in the lungs mitigated the CAP-induced decrease in glucose tolerance and insulin sensitivity in LICD. Our results demonstrate that circadian dyssynchrony is a novel susceptibility state for PM2.5 and suggest that PM2.5 by inducing pulmonary oxidative stress increases glucose intolerance and insulin resistance in circadian dyssynchrony.

17.
Front Neurol ; 14: 1105463, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36908590

RESUMO

Restless legs syndrome (RLS) is a sensorimotor disorder with a obvious circadian rhythm, as its symptoms often occur or worsen only in the evening or at night. The mechanisms behind the rhythms of RLS have not yet been fully elucidated. This review explores possible causes for the circadian fluctuations of the symptomatology, including the levels of iron, dopamine, melatonin, melanocortin, and thyroid-stimulating hormone in the brain, as well as conditions such as peripheral hypoxia and microvascular function disorders. The metabolic disturbances of the substances above can create a pathological imbalance, which is further aggravated by physiological fluctuations of circadian rhythms, and results in the worsening of RLS symptoms at night. The review concludes with the suggestions for RLS treatment and research directions in the future.

18.
Front Plant Sci ; 14: 1046235, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36909399

RESUMO

Dioecy system is an important strategy for maintaining genetic diversity. The transcription factor MeGI, contributes to dioecy by promoting gynoecium development in Diospyros lotus and D. kaki. However, the function of MeGI in D. oleifera has not been identified. In this study, we confirmed that MeGI, cloned from D. oleifera, repressed the androecium development in Arabidopsis thaliana. Subsequently, chromatin immunoprecipitation-sequencing (ChIP-seq), DNA affinity purification-sequencing (DAP-seq), and RNA-seq were used to uncover the gene expression response to MeGI. The results showed that the genes upregulated and downregulated in response to MeGI were mainly enriched in the circadian rhythm-related and flavonoid biosynthetic pathways, respectively. Additionally, the WRKY DNA-binding protein 28 (WRKY28) gene, which was detected by ChIP-seq, DAP-seq, and RNA-seq, was emphasized. WRKY28 has been reported to inhibit salicylic acid (SA) biosynthesis and was upregulated in MeGI-overexpressing A. thaliana flowers, suggesting that MeGI represses the SA level by increasing the expression level of WRKY28. This was confirmed that SA level was lower in D. oleifera female floral buds than male. Overall, our findings indicate that the MeGI mediates its sex control function in D. oleifera mainly by regulating genes in the circadian rhythm, SA biosynthetic, and flavonoid biosynthetic pathways.

19.
Zhongguo Zhong Yao Za Zhi ; 48(3): 569-578, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36872219

RESUMO

Circadian rhythm is an internal regulatory mechanism formed in organisms in response to the circadian periodicity in the environment, which modulates the pathophysiological events, occurrence and development of diseases, and the response to treatment in mammals. It significantly influences the susceptibility, injury, and recovery of ischemic stroke, and the response to therapy. Accumulating evidence indicates that circadian rhythms not only regulate the important physiological factors of ischemic stroke events, such as blood pressure and coagulation-fibrinolysis system, but also participate in the immuno-inflammatory reaction mediated by glial cells and peripheral immune cells after ischemic injury and the regulation of neurovascular unit(NVU). This article aims to link molecular, cellular, and physiological pathways in circadian biology to the clinical consequences of ischemic stroke and to illustrate the impact of circadian rhythms on ischemic stroke pathogenesis, the regulation of NVU, and the immuno-inflammatory responses. The regulation of circadian rhythm by traditional Chinese medicine is reviewed, and the research progress of traditional Chinese medicine intervention in circadian rhythm is summarized to provide a reasonable and valuable reference for the follow-up traditional Chinese medicine research and molecular mechanism research of circadian rhythm.


Assuntos
AVC Isquêmico , Animais , Medicina Tradicional Chinesa , Ritmo Circadiano , Coagulação Sanguínea , Pressão Sanguínea , Mamíferos
20.
Front Immunol ; 14: 980711, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36875134

RESUMO

Background and objective: A recent study has suggested that circadian rhythm has an important impact on the immunological effects induced by Bacillus Calmette-Guérin (BCG) vaccination. The objective of this study was to evaluate whether the timing of BCG vaccination (morning or afternoon) affects its impact on severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections and clinically relevant respiratory tract infections (RTIs). Methods: This is a post-hoc analysis of the BCG-CORONA-ELDERLY (NCT04417335) multicenter, placebo-controlled trial, in which participants aged 60 years and older were randomly assigned to vaccination with BCG or placebo, and followed for 12 months. The primary endpoint was the cumulative incidence of SARS-CoV-2 infection. To assess the impact of circadian rhythm on the BCG effects, participants were divided into four groups: vaccinated with either BCG or placebo in the morning (between 9:00h and 11:30h) or in the afternoon (between 14:30h and 18:00h). Results: The subdistribution hazard ratio of SARS-CoV-2 infection in the first six months after vaccination was 2.394 (95% confidence interval [CI], 0.856-6.696) for the morning BCG group and 0.284 (95% CI, 0.055-1.480) for the afternoon BCG group. When comparing those two groups, the interaction hazard ratio was 8.966 (95% CI, 1.366-58.836). In the period from six months until 12 months after vaccination cumulative incidences of SARS-CoV-2 infection were comparable, as well as cumulative incidences of clinically relevant RTI in both periods. Conclusion: Vaccination with BCG in the afternoon offered better protection against SARS-CoV-2 infections than BCG vaccination in the morning in the first six months after vaccination.


Assuntos
COVID-19 , Mycobacterium bovis , Infecções Respiratórias , Idoso , Humanos , Pessoa de Meia-Idade , Vacina BCG , SARS-CoV-2 , Ritmo Circadiano , Vacinação
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