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1.
Ecotoxicol Environ Saf ; 248: 114303, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36403304

RESUMO

Zinc is an essential nutrient for life, but over-accumulation can result in toxicity. Anthropogenic activities can increase zinc concentrations in aquatic environments (e.g., to ∼0.46-1.00 mg/L), which are above the safe level of 0.1 mg/L. We investigated the behavior and physiology of zebrafish (Danio rerio) in response to environment-related exposure to zinc chloride at 0.0 (Ctrl), 1.0 (ZnCl2-low) and 1.5 (ZnCl2-high) mg/L for 6 weeks (the zinc conversion ratio of zinc chloride is ∼0.48 and the nominal (measured) values were: Ctrl, 0 (∼0.01); ZnCl2-low, 0.48 (∼0.51); ZnCl2-high, 0.72 (∼0.69) mg/L). Low-zinc exposure resulted in significantly increased locomotion and fast moving behaviors, while high-zinc exposure resulted in significantly increased aggression and freezing frequency. Single cell RNA-seq of neurons, astrocytes, and oligodendrocytes of the brain revealed expression of genes related to ion transport, neuron generation, and immunomodulation that were heterogeneously regulated by zinc exposure. Astrocyte-induced central nervous system inflammation potentially integrated neurotoxicity and behavior. Integrated analyses of brain and hepatic transcriptional signatures showed that genes (and pathways) dysregulated by zinc were associated with sensory functions, circadian rhythm, glucose and lipid metabolism, and amyloid ß-protein clearance. Our results showed that environment-related zinc contamination can be heterogeneously toxic to brain cells and can disturb coordination of brain-liver physiology. This may disrupt neurobehavior and cause a neurodegeneration-like syndrome in adult zebrafish.


Assuntos
Transtornos Cronobiológicos , Peixe-Zebra , Animais , Zinco/toxicidade , Peptídeos beta-Amiloides , Encéfalo , Agressão , Fígado
2.
Compr Physiol ; 12(4): 4185-4214, 2022 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-36073751

RESUMO

Circadian rhythms are endogenously generated, daily patterns of behavior and physiology that are essential for optimal health and disease prevention. Disruptions to circadian timing are associated with a host of maladies, including metabolic disease and obesity, diabetes, heart disease, cancer, and mental health disturbances. The circadian timing system is hierarchically organized, with a master circadian clock located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus and subordinate clocks throughout the CNS and periphery. The SCN receives light information via a direct retinal pathway, synchronizing the master clock to environmental time. At the cellular level, circadian rhythms are ubiquitous, with rhythms generated by interlocking, autoregulatory transcription-translation feedback loops. At the level of the SCN, tight cellular coupling maintains rhythms even in the absence of environmental input. The SCN, in turn, communicates timing information via the autonomic nervous system and hormonal signaling. This signaling couples individual cellular oscillators at the tissue level in extra-SCN brain loci and the periphery and synchronizes subordinate clocks to external time. In the modern world, circadian disruption is widespread due to limited exposure to sunlight during the day, exposure to artificial light at night, and widespread use of light-emitting electronic devices, likely contributing to an increase in the prevalence, and the progression, of a host of disease states. The present overview focuses on the circadian control of endocrine secretions, the significance of rhythms within key endocrine axes for typical, homeostatic functioning, and implications for health and disease when dysregulated. © 2022 American Physiological Society. Compr Physiol 12: 1-30, 2022.


Assuntos
Transtornos Cronobiológicos , Relógios Circadianos , Doenças Metabólicas , Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Humanos , Núcleo Supraquiasmático/fisiologia
3.
Nervenarzt ; 93(9): 873-881, 2022 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-35881187

RESUMO

BACKGROUND: Numerous symptoms of bipolar disorder are regulated by the circadian rhythm. Because of this association it is assumed that disruption of the circadian rhythm may be part of the pathomechanism of bipolar disorder. OBJECTIVES: A comparison and subsequent critical discussion of the current data situation on chronobiological aspects of bipolar disorder are presented. METHODS: A narrative literature search was carried out and the main findings are presented in a summarized form. RESULTS: There are a large number of animal and human studies investigating the connection between disorders of the circadian rhythm and bipolar disorder. Especially chronotype, the environmental factor light and sleep disorders seem to be associated with the development of bipolar disorder. CONCLUSIONS: The neurobiology of bipolar disorder shows numerous chronobiological aspects. There is evidence for a direct connection of disruption of the circadian rhythm and development and progression of bipolar disorder; however, at present there is no proof for the specificity of these findings for bipolar disorder. Future studies should consolidate the evidence on the impact of disorders of the circadian rhythm on the pathomechanism of bipolar disorder.


Assuntos
Transtorno Bipolar , Transtornos Cronobiológicos , Transtornos do Sono-Vigília , Animais , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico , Transtornos Cronobiológicos/complicações , Transtornos Cronobiológicos/diagnóstico , Ritmo Circadiano , Humanos , Sono , Transtornos do Sono-Vigília/diagnóstico
4.
Toxicol Appl Pharmacol ; 451: 116172, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35863504

RESUMO

Methamphetamine (METH) abuse is a significant public health concern globally. Cardiac toxicity is one of the important characteristics of METH, in addition to its effects on the nervous system. However, to date, research on the cardiotoxic injury induced by METH consumption has been insufficient. To systematically analyze the potential molecular mechanism of cardiac toxicity in METH-associated heart failure (HF), a rat model was constructed with a dose of 10 mg/kg of METH consumption. Cardiac function was evaluated by echocardiography, and HE staining was used to clarify the myocardial histopathological changes. Integrated analyses, including mRNA, miRNA and lncRNA, was performed to analyze the RNA expression profile and the potential molecular mechanisms involved in METH-associated HF. The results showed that METH caused decreased myocardial contractility, with a decreased percent ejection fraction (%EF). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of the RNAs with expression changes revealed abnormal circadian rhythm regulation in the METH groups, with circadian rhythm-related genes and their downstream effectors expressed differentially, especially the aryl hydrocarbon receptor nuclear translocator-like (Arntl). Competing endogenous RNA (ceRNA) networks associated with circadian rhythm, including Arntl, was also observed. Therefore, this study revealed that long-term METH consumption was associated with the HF in a rat model by decreasing the %EF, and that the abnormal circadian rhythm could provide new directions for investigating the METH-associated HF, and that the differentially expressed genes in this model could provide candidate genes for the identification and assessment of cardiac toxicity in METH-associated HF, which is fundamental for further understanding of the disease.


Assuntos
Transtornos Cronobiológicos , Insuficiência Cardíaca , Metanfetamina , MicroRNAs , RNA Longo não Codificante , Fatores de Transcrição ARNTL/genética , Animais , Cardiotoxicidade , Redes Reguladoras de Genes , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/genética , Metanfetamina/toxicidade , MicroRNAs/genética , RNA Longo não Codificante/genética , Ratos , Transcriptoma
5.
J Affect Disord ; 315: 42-47, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35878843

RESUMO

BACKGROUND: Circadian dysregulation has long been thought to be a key component in the pathophysiology of bipolar disorder (BD). However, it remains unclear whether this dysregulation constitutes a risk factor, manifestation, or consequence of BD. This study aimed to compare dim light melatonin secretion patterns between unaffected offspring of parents with BD (OBD) and offspring of control parents (OCP). METHODS: This case-control study included unaffected OBD (mean age 14.0 years; male 50.0 %) and age- and sex-matched OCP (mean age 13.0 years; male: 43.5 %). Seventeen saliva samples were collected in dim light conditions. Dim light melatonin onset (DLMO), phase angles, and area under the curve (AUC) were calculated. RESULTS: 185 saliva samples from 12 OBD (n = 12) and 741 from OCP (n = 46) were collected. Unaffected OBD had a significant lower nocturnal melatonin level (14.8 ± 4.6 vs. 20.3 ± 11.7 pg/mL) and a smaller melatonin AUC within two hours after DLMO (35.5 ± 11.3 vs. 44.6 ± 18.1 pg/mL) but a significant larger phase angle between DLMO and sleep onset (2.2 ± 1.0 vs. 1.4 ± 1.2 h) than OCP. There was no significant between-group difference in DLMO. The graphic illustrations showed a considerably flattened melatonin secretion in unaffected OBD. LIMITATIONS: The main limitations include lack of 24-h dim melatonin secretion measurement, large age range of participants, and small sample size. CONCLUSIONS: These findings suggest that unaffected OBD already presented with circadian rhythm dysregulations. Future investigations are needed to clarify the role of abnormal melatonin secretion in the onset of BD.


Assuntos
Transtorno Bipolar , Transtornos Cronobiológicos , Melatonina , Adolescente , Estudos de Casos e Controles , Ritmo Circadiano/fisiologia , Humanos , Luz , Masculino , Pais , Saliva , Sono/fisiologia
6.
BMC Neurol ; 22(1): 272, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864449

RESUMO

BACKGROUND: Circadian rhythm disorders (CRDs) are closely associated with the occurrence and development of various diseases, such as inflammatory and cardiovascular diseases, as well as tumors. The impact of a CRD on bodily health is a complex and comprehensive process, and its molecular mechanisms and signaling pathways are still unclear. We therefore aimed to investigate the molecular mechanism variation and adverse outcomes associated with CRDs in a prospective cohort of CRD cases and controls at term using multiomics data. The study has been tasked with developing a precise health promotion model for the prevention and management of CRDs. METHODS: This will be a 5-year prospective cohort study centered on the health management of individuals with CRDs. One hundred volunteers were recruited and had undergone baseline specimen collection, health examination, and health assessment. All of them will be followed up every year using the same protocol, and their biological specimens will be subjected to multiomics analysis after standardized processing. DISCUSSION: Longitudinal health examination, health assessment, and multiomics data will be analyzed to study the impact of CRDs on the volunteers' health status. The results of this study will promote the development of targeted health management programs based on precision medicine. TRIAL REGISTRATION: The clinical study registration has been completed (Trial Registration No. ChiCTR2100047242 ).


Assuntos
Transtornos Cronobiológicos , Ritmo Circadiano , Estudos de Coortes , Nível de Saúde , Humanos , Estudos Prospectivos
7.
Int J Mol Sci ; 23(15)2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35897788

RESUMO

The circadian clock (CC) is a daily system that regulates the oscillations of physiological processes and can respond to the external environment in order to maintain internal homeostasis. For the functioning of the CC, the clock genes (CG) act in different metabolic pathways through the clock-controlled genes (CCG), providing cellular regulation. The CC's interruption can result in the development of different diseases, such as neurodegenerative and metabolic disorders, as well as cancer. Leukemias correspond to a group of malignancies of the blood and bone marrow that occur when alterations in normal cellular regulatory processes cause the uncontrolled proliferation of hematopoietic stem cells. This review aimed to associate a deregulated CC with the manifestation of leukemia, looking for possible pathways involving CG and their possible role as leukemic biomarkers.


Assuntos
Transtornos Cronobiológicos , Relógios Circadianos , Leucemia , Neoplasias , Biomarcadores , Relógios Circadianos/genética , Ritmo Circadiano/genética , Humanos , Leucemia/genética
8.
Food Chem ; 394: 133500, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35749873

RESUMO

Obesity is one of the circadian rhythm disorders (CRD)-mediated metabolic disorder syndromes. Pu-erh tea is a viable dietary intervention for CRD, however its effect on CRD-induced obesity is unclear. Here, we found that Pu-erh tea improved obesity in CRD-induced mice, which stemmed from the production of Cinnabarinic acid (CA). CA promoted adipose tissue lipolysis and thermogenic response (HSL, ATGL, Pparα, CKB, UCP1) and increased adipocyte sensitivity to hormones and neurotransmitters by targeting the expression of adipose tissue receptor proteins (Q6KAT8, P51655, A2AKQ0, M0QWX7, Q6ZQ33, and mGluR4). This improved mitochondrial activity and facilitated adipose tissue metabolic processes, thereby accelerating glucolipid metabolism. Also, CA-induced alterations in gut microbes and short-chain fatty acids further improved CRD-mediated lipid accumulation. These results suggest that the increase of CA caused by Pu-erh tea, targeted to adipose tissue via the metabolite-blood circulation-adipose tissue axis, maybe a key mechanism for reducing the development of CRD-induced obesity.


Assuntos
Transtornos Cronobiológicos , Chá , Animais , Camundongos , Obesidade/tratamento farmacológico , Obesidade/genética , Oxazinas
9.
Nutrients ; 14(11)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35684108

RESUMO

Circadian rhythm disruption is detrimental and results in adverse health consequences. We used a multi-omics profiling approach to investigate the effects of Cyclocarya paliurus flavonoid (CPF)-enriched diets on gut microbiota, metabolites, and hypothalamus clock genes in mice with induced circadian rhythm disruption. It was observed that CPF supplementation altered the specific composition and function of gut microbiota and metabolites induced by circadian rhythm disruption. Analysis showed that the abundance of Akkermansia increased, while the abundance of Clostridiales and Ruminiclostridium displayed a significant downward trend after the CPF intervention. Correlation analysis also revealed that these gut microbes had certain correlations with the metabolites, suggesting that CPFs help the intestinal microbiota to repair the intestinal environment and modulate the release of some beneficial metabolites. Notably, single-cell RNA-seq revealed that CPF supplementation significantly regulated the expression of genes associated with circadian rhythm, myelination, and neurodegenerative diseases. Altogether, these findings highlight that CPFs may represent a promising dietary therapeutic strategy for treating circadian rhythm disruption.


Assuntos
Transtornos Cronobiológicos , Microbioma Gastrointestinal , Juglandaceae , Animais , Ritmo Circadiano , Modelos Animais de Doenças , Flavonoides/metabolismo , Flavonoides/farmacologia , Hipotálamo , Juglandaceae/metabolismo , Camundongos
10.
J Cell Physiol ; 237(8): 3239-3256, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35696609

RESUMO

The circadian system is responsible for internal functions and regulation of the organism according to environmental cues (zeitgebers). Circadian rhythm dysregulation or chronodisruption has been associated with several diseases, from mental to autoimmune diseases, and with life quality change. Following this, some therapies have been developed to correct circadian misalignments, such as light therapy and chronobiotics. In this manuscript, we describe the circadian-related diseases so far investigated, and studies reporting relevant data on this topic, evidencing this relationship, are included. Despite the actual limitations in published work, there is clear evidence of the correlation between circadian rhythm dysregulation and disease origin/development, and, in this way, clock-related therapies emerge as great progress in the clinical field. Future improvements in such interventions can lead to the development of successful chronotherapy strategies, deeply contributing to enhanced therapeutic outcomes.


Assuntos
Transtornos Cronobiológicos , Ritmo Circadiano , Doença , Transtornos Cronobiológicos/fisiopatologia , Transtornos Cronobiológicos/terapia , Ritmo Circadiano/fisiologia , Humanos
11.
Integr Cancer Ther ; 21: 15347354221096080, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35575281

RESUMO

Circadian genes regulate several physiological functions such as circadian rhythm and metabolism and participate in the cytogenesis and progression of various malignancies. The abnormal expression of these genes in non-small cell lung cancer (NSCLC) is closely related to the clinicopathological features of NSCLC and may promote or inhibit NSCLC progression. Circadian rhythm disorders and clock gene abnormalities may increase the risk of lung cancer in some populations. We collected 15 circadian genes in NSCLC, namely PER1, PER2, PER3, TIMELESS, Cry1, Cry2, CLOCK, BMAL1/ARNTL-1, ARNTL2, NPAS2, NR1D1(REV-ERB), DEC1, DEC2, RORα, and RORγ, and determined their relationships with the clinicopathological features of patients and the potential mechanisms promoting or inhibiting NSCLC progression. We also summarized the studies on circadian rhythm disorders and circadian genes associated with lung cancer risk. The present study aimed to provide theoretical support for the future exploration of new therapeutic targets and for the primary prevention of NSCLC from the perspective of circadian genes. Interpretation of circadian rhythms in lung cancer could guide further lung cancer mechanism research and drug development that could lead to more effective treatments and improve patient outcomes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Transtornos Cronobiológicos , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/genética , Ritmo Circadiano/genética , Humanos , Neoplasias Pulmonares/genética
12.
J Neurodev Disord ; 14(1): 33, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35610565

RESUMO

BACKGROUND: Regulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer's disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging. METHODS: The present study examined the impacts of RCAN1 deficiency and overexpression on the photic entrainment, circadian periodicity, intensity and distribution, diurnal patterning, and circadian rhythmicity of wheel running in young (3-6 months old) and aged (9-14 months old) mice of both sexes. RESULTS: We found that daily RCAN1 levels in the hippocampus and suprachiasmatic nucleus (SCN) of light-entrained young mice are generally constant and that balanced RCAN1 expression is necessary for normal circadian locomotor activity rhythms. While the light-entrained diurnal period was unaltered, RCAN1-null and RCAN1-overexpressing mice displayed lengthened endogenous (free-running) circadian periods like mouse models of AD and aging. In light-entrained young mice, RCAN1 deficiency and overexpression also recapitulated the general hypoactivity, diurnal rest-wake pattern fragmentation, and attenuated amplitudes of circadian activity rhythms reported in DS, preclinical and clinical AD, healthily aging individuals, and rodent models thereof. Under constant darkness, RCAN1-null and RCAN1-overexpressing mice displayed altered locomotor behavior indicating circadian clock dysfunction. Using the Dp(16)1Yey/+ (Dp16) mouse model for DS, which expresses three copies of Rcan1, we found reduced wheel running activity and rhythmicity in both light-entrained and free-running young Dp16 mice like young RCAN1-overexpressing mice. Critically, these diurnal and circadian deficits were rescued in part or entirely by restoring Rcan1 to two copies in Dp16 mice. We also found that RCAN1 deficiency but not RCAN1 overexpression altered protein levels of the clock gene Bmal1 in the SCN. CONCLUSIONS: Collectively, this study's findings suggest that both loss and aberrant gain of RCAN1 precipitate anomalous light-entrained diurnal and circadian activity patterns emblematic of DS, AD, and possibly aging.


Assuntos
Envelhecimento , Doença de Alzheimer , Proteínas de Ligação ao Cálcio , Transtornos Cronobiológicos , Proteínas de Ligação a DNA , Síndrome de Down , Proteínas Musculares , Envelhecimento/fisiologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Transtornos Cronobiológicos/genética , Transtornos Cronobiológicos/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Síndrome de Down/genética , Síndrome de Down/metabolismo , Feminino , Masculino , Camundongos , Atividade Motora/fisiologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Núcleo Supraquiasmático/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
Mol Nutr Food Res ; 66(14): e2101170, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35598297

RESUMO

SCOPE: Plant polysaccharides are thought to have a prebiotic effect, promoting the growth of probiotics, which may regulate circadian rhythms. This study evaluates the regulation of peach polysaccharides (PPS) on circadian rhythm disturbance through intestinal microbiota by a mouse model. METHODS AND RESULTS: PPS is administered to mice with circadian rhythm disturbance for 4 weeks. The study finds that PPS ameliorated the structural disorder of intestinal microbiota induced by continuous darkness, decreasing the ratio of Firmicutes/Bacteroidetes (F/B), thereby regulating furfural degradation, penicillin and cephalosporin biosynthesis, and antibiotic biosynthesis. Single-cell transcriptomics is used to determine the type of hypothalamus cells and the expression of clock genes in mice, showing that the number of astrocytes and oligoendrocytes cells in the hypothalamus of the transplanted mice is up-regulated, and the expression of neuroprotective genes such as Sox9 and Mobp increased. In addition, clock genes such as Cry2 and Per3 show significant callback. CONCLUSION: This study shows that PPS can ameliorate the imbalance of intestinal microbiota and cell dysfunction caused by circadian rhythm disorder, suggesting that PPS is a feasible strategy for the prevention and treatment of circadian rhythm disorder and related cognitive impairment.


Assuntos
Transtornos Cronobiológicos , Relógios Circadianos , Prunus persica , Animais , Relógios Circadianos/genética , Ritmo Circadiano/fisiologia , Camundongos , Polissacarídeos/farmacologia , Transcriptoma
14.
J Agric Food Chem ; 70(18): 5610-5623, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35475616

RESUMO

Pu-erh tea is a healthy beverage rich in phytochemicals, and its effect on the risk of inducing circadian rhythm disorders (CRD) is unclear. In this study, healthy mice were given water or 0.25% (w/v) Pu-erh tea for 7 weeks, followed by a 40 day disruption of the light/dark cycle. CRD caused dysregulation of neurotransmitter secretion and clock gene oscillations, intestinal inflammation, and disruption of intestinal microbes and metabolites. Pu-erh tea boosted the indole and 5-hydroxytryptamine pathways of tryptophan metabolism via the gut-liver-brain axis. Furthermore, its metabolites (e.g., IAA, Indole, 5-HT) enhanced hepatic glycolipid metabolism and down-regulated intestinal oxidative stress by improving the brain hormone release. Tryptophan metabolites and bile acids also promoted liver lipid metabolism and inhibited intestinal inflammation (MyD88/NF-κB) via the enterohepatic circulation. Collectively, 0.25% (w/v) Pu-erh tea has the potential to prevent CRD by promoting indole and 5-HT pathways of tryptophan metabolism and signaling interactions in the gut-liver-brain axis.


Assuntos
Transtornos Cronobiológicos , Microbioma Gastrointestinal , Animais , Ritmo Circadiano , Inflamação , Camundongos , Serotonina , Chá/metabolismo , Triptofano
15.
J Cardiovasc Transl Res ; 15(5): 985-997, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35257279

RESUMO

Circadian rhythm disorders can accelerate atherosclerosis. This study aimed to determine the role of circadian disordered macrophages in atherosclerotic development. Mice were divided into NC group (normal circadian rhythm), L24 group (constant light), D12L12 group (weekly shift light/dark cycle), and D24 group (constant dark). Atherosclerotic progression was significantly accelerated in L24, D12L12, and D24 groups. Peritoneal macrophages from circadian disruption groups exhibited enhanced cytokine secretion and foam cell formation. Migration and proliferation of vascular smooth muscle cells (VSMCs) were increased under the conditioned medium of circadian disordered macrophages. The blockade of CD36 markedly inhibited foam cell formation. Compared with blocking CD36 or TLR4 alone, the co-inhibition of CD36 and TLR4 in macrophages further reduced cytokine secretion and more effectively inhibited VSMC migration and proliferation. In conclusion, the activation of CD36 and TLR4 in circadian disordered macrophages promotes foam cell formation and cytokine secretion and enhances VSMC migration and proliferation. Circadian rhythm disorders promote lipid uptake and cytokine secretion of macrophages by regulating CD36 and TLR4, and enhance VSMC migration and proliferation through the paracrine effect of macrophages.


Assuntos
Aterosclerose , Transtornos Cronobiológicos , Animais , Camundongos , Aterosclerose/metabolismo , Antígenos CD36/metabolismo , Proliferação de Células , Transtornos Cronobiológicos/metabolismo , Citocinas/metabolismo , Células Espumosas/metabolismo , Lipoproteínas LDL , Macrófagos/metabolismo , Músculo Liso Vascular/metabolismo , Receptor 4 Toll-Like/metabolismo , Ritmo Circadiano
16.
Physiol Behav ; 249: 113772, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35247442

RESUMO

BACKGROUND: Circadian rhythm disorders are severe threats to human health. The negative impact of circadian rhythm disorders on tissues/organs has not been systematically analyzed. Therefore, there is an urgent need to evaluate the damage caused by circadian rhythm disorders and explore the possible mechanisms. METHODS: Six-week-old male mice were divided into the control (Con) group (normal circadian rhythm), L24 group (constant light), D12L12 group (weekly shift light/dark cycle), and D24 group (constant dark). Body weight was recorded every 10 days. Ninety days after model construction, the serum lipid and cytokine level, liver function, fat accumulation, carotid artery stenosis, and cardiomyopathological changes were detected in mice. Macrophages in the liver, subscapular fat, and heart tissues were labeled with immunofluorescence staining. Mouse peritoneal macrophages were then isolated. Inflammatory cytokine levels were measured in the macrophage supernatant. The ability of macrophages to form foam cells was also tested. The supernatant from macrophages in different groups was added to AML12 (hepatocytes), 3T3-L1 (preadipocytes), or HL-1 (cardiomyocytes). Effects of conditioned media on recipient cells were determined. RESULTS: Body weight, serum lipids and cytokines, subscapular fat accumulation, liver enzymes, carotid artery stenosis, and myocardial fibrosis levels of the L24, D12L12, and D24 groups mice were significantly higher than those in the Con group. Macrophages were significantly increased in the liver, heart, and subscapular fat of mice with circadian rhythmdisorders. Cytokine secretion by peritoneal macrophages was enhanced in the L24, D12L12, and D24 groups. Under oxidized low density lipoprotein (oxLDL) stimulation, macrophages with circadian rhythm disorders are more likely to form foam cells. Conditioned media from the L24, D12L12, and D24 groups significantly promoted AML12 apoptosis and lipid intake, accelerated the adipogenic differentiation of 3T3-L1, and up-regulated collagen I in HL-1. CONCLUSION: These findings reveal that macrophages are increased in the tissues/organs under circadian rhythm disorders, and these macrophages could aggravate obesity, promote liver disease, accelerate atherosclerosis, and increase myocardial fibrosis through the paracrine effect.


Assuntos
Estenose das Carótidas , Transtornos Cronobiológicos , Animais , Peso Corporal , Estenose das Carótidas/patologia , Transtornos Cronobiológicos/patologia , Ritmo Circadiano , Meios de Cultivo Condicionados/farmacologia , Citocinas , Fibrose , Macrófagos/patologia , Masculino , Camundongos
17.
Sci Rep ; 12(1): 2434, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165331

RESUMO

Emerging evidence suggests that disruption of circadian rhythmicity contributes to development of comorbid depression, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM). Physical exercise synchronizes the circadian system and has ameliorating effects on the depression- and anxiety-like phenotype induced by circadian disruption in mice and sand rats. We explored the beneficial effects of voluntary wheel running on daily rhythms, and the development of depression, T2DM, and CVD in a diurnal animal model, the fat sand rat (Psammomys obesus). Voluntary exercise strengthened general activity rhythms, improved memory and lowered anxiety- and depressive-like behaviors, enhanced oral glucose tolerance, and decreased plasma insulin levels and liver weight. Animals with access to a running wheel had larger heart weight and heart/body weight ratio, and thicker left ventricular wall. Our results demonstrate that exercising ameliorates pathological-like daily rhythms in activity and blood glucose levels, glucose tolerance and depressive- and anxiety-like behaviors in the sand rat model, supporting the important role of physical activity in modulating the "circadian syndrome" and circadian rhythm-related diseases. We suggest that the utilization of a diurnal rodent animal model may offer an effective way to further explore metabolic, cardiovascular, and affective-like behavioral changes related to chronodisruption and their underlying mechanisms.


Assuntos
Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/terapia , Transtornos Cronobiológicos/complicações , Transtornos Cronobiológicos/terapia , Ritmo Circadiano , Depressão/complicações , Depressão/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Terapia por Exercício/métodos , Condicionamento Físico Animal/métodos , Animais , Ansiedade/complicações , Ansiedade/fisiopatologia , Ansiedade/terapia , Glicemia/análise , Doenças Cardiovasculares/fisiopatologia , Transtornos Cronobiológicos/fisiopatologia , Depressão/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Modelos Animais de Doenças , Gerbillinae , Teste de Tolerância a Glucose , Insulina/sangue , Locomoção , Masculino , Ratos , Núcleo Supraquiasmático/fisiopatologia , Resultado do Tratamento
19.
J Agric Food Chem ; 70(6): 1890-1901, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35112849

RESUMO

Green tea polyphenols (GTP) have similar activities as prebiotics, which effectively regulate the structure of intestinal flora and affect their metabolic pathways. The intestinal flora is closely related to the host's circadian rhythm, and the supplementation with GTP may be an effective way to improve circadian rhythm disorders. In this study, we established a mouse model of circadian rhythm disturbance of anthropogenic flora to investigate the regulation mechanism of GTP on the host circadian rhythms. After 4 weeks of GTP administration, the results showed that GTP significantly alleviated the structural disorder of intestinal microbiota, thus effectively regulating related metabolites associated with brain nerves and circadian rhythms. Moreover, single-cell transcription of the mouse hypothalamus suggested that GTP up-regulated the number of astrocytes and oligodendrocytes and adjusted the expression of core clock genes Csnk1d, Clock, Per3, Cry2, and BhIhe41 caused by circadian disruption. Therefore, this study provided evidence that GTP can improve the physiological health of hosts with the circadian disorder by positively affecting intestinal flora and related metabolites and regulating circadian gene expression.


Assuntos
Transtornos Cronobiológicos , Microbioma Gastrointestinal , Animais , Hipotálamo , Camundongos , Polifenóis , Chá
20.
Environ Sci Pollut Res Int ; 29(19): 28062-28069, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34988815

RESUMO

In 2020, the world gained dramatic experience of the development of the 2019 coronavirus disease pandemic (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2). Recent researches notice an increasing prevalence of anxiety and circadian rhythm disorders during COVID-19 pandemic. The aim of the study was describing clinical features of circadian rhythm disorders and the level of anxiety in persons who have had COVID-19. We have conducted a cohort retrospective study that included 278 patients who were divided into 2 study groups according to medical history: group 1 includes patients with a history of COVID-19; group 2 consists of patients who did not have clinically confirmed COVID-19 and are therefore considered not to have had this disease. To objectify circadian rhythm disorders, they were verified in accordance with the criteria of the International Classification of Sleep Disorders-3. The level of anxiety was assessed by the State-Trait Anxiety Inventory. The most common circadian rhythm disorders were sleep phase shifts. We found that COVID-19 in the anamnesis caused a greater predisposition of patients to the development of circadian rhythm disorders, in particular delayed sleep phase disorder. In addition, it was found that after COVID-19 patients have increased levels of both trait and state anxiety. In our study, it was the first time that relationships between post-COVID-19 anxiety and circadian rhythm disorders had been indicated. Circadian rhythm disorders are associated with increased trait and state anxiety, which may indicate additional ways to correct post-COVID mental disorders and their comorbidity with sleep disorders.


Assuntos
COVID-19 , Transtornos Cronobiológicos , Transtornos do Sono-Vigília , Ansiedade/epidemiologia , COVID-19/epidemiologia , Ritmo Circadiano , Humanos , Saúde Mental , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Transtornos do Sono-Vigília/epidemiologia , Inquéritos e Questionários
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