Search Results (12)

Camellia’s ornamental value is constrained by its natural winter–spring flowering period. Although the discovery of Camellia azalea provides important germplasm resources for developing cultivars with year-round flowering, the molecular mechanisms underlying flowering time variation remain unclear. Here, we investigated three germplasms with distinct flowering patterns: winter–spring flowering Camellia japonica ‘Tieke Baozhu’, summer–autumn flowering Camellia azalea, and their hybrid Camellia ‘Lingnan Yuanbao’ inheriting the latter’s flowering traits. Integrated transcriptomic and metabolomic analyses revealed that differentially expressed genes (DEGs) and metabolites (DAMs) were mainly enriched in the pathways related to photoperiod regulation, plant hormone synthesis and signal transduction and flavonoid synthesis. The transcription factor (TF) analysis revealed that the bHLH and MYB TF families were significantly differentially expressed in different Camellia germplasm, suggesting their potential involvement in the regulation of flowering time through the plant hormone signal transduction and photoperiod pathway. Meanwhile, photoperiod regulation related genes, including Cryptochrome circadian regulator (CRY), Timing of CAB expression 1 (TOC1), and phytochrome interacting factor 3 (PIF3), showed significant expression differences, further confirming the photoperiod pathway’s crucial regulatory function. In terms of plant hormone levels, there were significant differences in the levels of gibberellin (GA), abscisic acid (ABA), and jasmonic acid (JA) among Camellia germplasm. The differential expression characteristics of DELLA (Asp-Glu-Leu-Leu-Ala) proteins indicated that the GA signal transduction pathway was one of the key factors regulating flowering time in Camellia. Additionally, metabolomics analyses showed significant differences in flavonoid metabolite content among Camellia germplasm, which was significantly correlated with the different developmental stages of the buds. Our findings provide a theoretical basis for the molecular breeding of everblooming Camellia cultivars, advancing the understanding of flowering regulation mechanism in ornamental species. Full article

High-altitude environments pose significant risks for insomnia development, which severely compromises both physiological health and occupational performance. To elucidate the mechanisms underlying altitude-induced sleep disruption and establish a validated animal model for therapeutic intervention development, we exposed Sprague-Dawley rats to hypobaric hypoxia (5500 m altitude equivalent: 308 mmHg, 20.37% O₂, PiO₂ 8.0 kPa) for 7 days. We employed continuous wireless telemetry to monitor EEG/EMG signals, with concurrent analysis of physiological parameters, blood biochemistry, histopathology, transcriptomics, and protein expression. Quantitative analyses demonstrated decreased caloric intake, transient body mass reduction, and immune-metabolic disturbances. While total sleep duration showed no significant variation, sleep architecture displayed elevated wakefulness periods, reduced active wakefulness, a decreasing trend of slow-wave sleep (SWS), and increased paradoxical sleep (PS) accompanied by attenuated circadian oscillations. The duration of SWS episodes was significantly shortened, indicating a sleep homeostasis imbalance that peaked on day 3. Biochemical profiling revealed reduced levels of antioxidant enzymes, elevated pro-inflammatory cytokines, and hypothalamic–pituitary–adrenal axis activation. Transcriptomic analyses identified the critical involvement of serotonergic/glutamatergic synaptic regulation, lipid metabolism, IL-17 signaling, and cortisol synthesis pathways. Western blot analyses confirmed OX2R upregulation, 5-HT1AR downregulation, and circadian gene dysregulation. Our findings demonstrate that hypobaric hypoxia induces sleep disruption via coordinated mechanisms involving oxidative stress, inflammatory activation, HPA axis hyperactivity, neurotransmitter imbalance, and circadian clock dysfunction, providing a robust preclinical model for mechanistic exploration and therapeutic target identification. Full article

DEHP is a plasticizer that is widely found in our water environment and poses a significant risk to the environment and human health. Long-term exposure to DEHP can cause endocrine disruption and interfere with the organism’s normal functioning. In order to explore the potential effects of DEHP on the development of biological brain tissues, this study used bioinformatics analysis to confirm the diagnostic and prognostic value of PER3 in gliomas and further validated the neurotoxicity of DEHP using methods such as behavioral experiments and molecular biology in zebrafish. The experimental findings revealed that the expression level of PER3 in diseased tissues was significantly lower than that in the control group. In addition, the expression level of PER3 was significantly correlated with immune cell infiltration, immune checkpoint genes, and oncogenes. Moreover, the ROC curve analysis showed that PER3 could accurately differentiate between GBM tissues and adjacent normal tissues. To further validate the neurotoxicity of DEHP, we analyzed the effects of DEHP exposure on zebrafish development and PER3 expression by behavioral experiments and molecular biology. The results showed that exposure to DEHP substantially altered both the behavioral responses and the gene expression profiles within the brain tissues of zebrafish. PCR results indicate that the expression of circadian rhythm factor PER3 was significantly reduced in the brains of zebrafish in the exposed group, and circadian dysregulation had a certain promoting effect on the development of glioma. The aim of this work was to investigate the potential effects of DEHP contamination in a water environment on organism brain development. It was demonstrated that PER3 is an effective early diagnostic marker, which is of great significance in the diagnosis and clinical prognosis of glioma, and that DEHP exposure can lead to a significant reduction in PER3 expression in zebrafish brain tissue. This study further proved that DEHP has a potential carcinogenic effect, which adds scientific evidence to the carcinogenicity study of DEHP. Full article

This study explores the role of circadian clock genes in the progression of astrocytic tumors, a prevalent type of brain tumor. The aim was to assess the expression patterns of these genes in relation to the tumor grade. Using microarray analysis, qRT-PCR, and methylation-specific PCR, we examined gene expression, DNA methylation patterns, and microRNA interactions in tumor samples from 60 patients. Our results indicate that the expression of key circadian clock genes, such as clock circadian regulator (CLOCK), protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2), protein kinase AMP-activated non-catalytic subunit beta 1 (PRKAB1), protein kinase AMP-activated non-catalytic subunit beta 2 (PRKAB2), period circadian regulator 1 (PER1), period circadian regulator 2 (PER2) and period circadian regulator 3 (PER3), varies significantly with the tumor grade. Notably, increased CLOCK gene expression and protein levels were observed in higher-grade tumors. DNA methylation analysis revealed that the promoter regions of PER1-3 genes were consistently methylated, suggesting a mechanism for their reduced expression. Our findings also underscore the complex regulatory mechanisms involving miRNAs, such as hsa-miR-106-5p, hsa-miR-20b-5p, and hsa-miR-30d-3p, which impact the expression of circadian clock-related genes. This underscores the importance of circadian clock genes in astrocytic tumor progression and highlights their potential as biomarkers and therapeutic targets. Further research is needed to validate these results and explore their clinical implications. Full article

Physiology disorders of the liver, as it is an important tissue in lipid metabolism, can cause fatty liver disease. The mechanism might be regulated by 17 circadian clock genes and 18 fat metabolism genes, together with a high-fat diet (HFD). Due to their rich nutritional and medicinal value, Chinese soft-shelled turtles (Trionyx sinensis) are very popular among the Chinese people. In the study, we aimed to investigate the influence of an HFD on the daily expression of both the core clock genes and the lipid metabolism genes in the liver tissue of the turtles. The two diets were formulated with 7.98% lipid (the CON group) and 13.86% lipid (the HFD group) to feed 180 juvenile turtles, which were randomly divided into two groups with three replicates per group and 30 turtles in each replicate for six weeks, and the diet experiment was administrated with a photophase regimen of a 24 h light/dark (12L:12D) cycle. At the end of the experiment, the liver tissue samples were collected from nine turtles per group every 3 h (zeitgeber time: ZT 0, 3, 6, 9, 12, 15, 18, 21 and 24) for 24 h to investigate the daily expression and correlation analysis of these genes. The results showed that 11 core clock genes [i.e., circadian locomotor output cycles kaput (Clock), brain and muscle arnt-like protein 1 and 2 (Bmal1/2), timeless (Tim), cryptochrome 1 (Cry2), period2 (Per2), nuclear factor IL-3 gene (Nfil3), nuclear receptor subfamily 1, treatment D, member 1 and 2 (Nr1d1/2) and retinoic acid related orphan receptor α/β/γ β and γ (Rorβ/γ)] exhibited circadian oscillation, but 6 genes did not, including neuronal PAS domain protein 2 (Npas2), Per1, Cry1, basic helix-loop-helix family, member E40 (Bhlhe40), Rorα and D-binding protein (Dbp), and 16 lipid metabolism genes including fatty acid synthase (Fas), diacylglycerol acyltransferase 1 (Dgat1), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), Low-density lipoprotein receptor-related protein 1-like (Ldlr1), Lipin 1 (Lipin1), Carnitine palmitoyltransferase 1A (Cpt1a), Peroxisome proliferator activation receptor α, β and γ (Pparα/β/γ), Sirtuin 1 (Sirt1), Apoa (Apoa1), Apolipoprotein B (Apob), Pyruvate Dehydrogenase kinase 4 (Pdk4), Acyl-CoA synthase long-chain1 (Acsl1), Liver X receptors α (Lxrα) and Retinoid X receptor, α (Rxra) also demonstrated circadian oscillations, but 2 genes did not, Scd and Acaca, in the liver tissues of the CON group. However, in the HFD group, the circadian rhythms’ expressional patterns were disrupted for the eight core clock genes, Clock, Cry2, Per2, Nfil3, Nr1d1/2 and Rorβ/γ, and the peak expression of Bmal1/2 and Tim showed delayed or advanced phases. Furthermore, four genes (Cry1, Per1, Dbp and Rorα) displayed no diurnal rhythm in the CON group; instead, significant circadian rhythms appeared in the HFD group. Meanwhile, the HFD disrupted the circadian rhythm expressions of seven fat metabolism genes (Fas, Cpt1a, Sirt1, Apoa1, Apob, Pdk4 and Acsl1). Meanwhile, the other nine genes in the HFD group also showed advanced or delayed expression peaks compared to the CON group. Most importantly of all, there were remarkably positive or negative correlations between the core clock genes and the lipid metabolism genes, and their correlation relationships were altered by the HFD. To sum up, circadian rhythm alterations of the core clock genes and the lipid metabolism genes were induced by the high-fat diet (HFD) in the liver tissues of T. sinensis. This result provides experimental and theoretical data for the mass breeding and production of T. sinensis in our country. Full article

Oxygen level is an important environmental factor affecting the circadian rhythm. However, little is known about the molecular mechanism by which clock genes regulate the circadian rhythm in fish under hypoxia. To explore changes in the transcription and expression of clock genes and related molecular regulatory mechanisms in pearl gentian grouper under hypoxia, liver transcriptome data were analyzed after exposure to acute hypoxic stress (dissolved oxygen 0.5 mg/L) for 1, 3, 6, and 9 h. miR-210 and m0044-5p inhibited the expression of period3 (per3) and casein kinase 1 delta b (csnk1db) in the core loop of the circadian clock, respectively. The nuclear receptor subfamily 1 group d member 1 (nr1d1) and RAR-related orphan receptor b (rorb) genes in the auxiliary loop were jointly up-regulated by three miRNAs (miR-144-3p/5p, miR-361-5p, and miR-133) and the transcription factor nuclear receptor subfamily 1 group d member 2 (Nr1d2). The pearl gentian grouper maintains the stability of circadian clock systems and normal physiological metabolism under hypoxic stress by regulating the transcriptional expression of these genes via miRNAs and transcription factors to improve hypoxic tolerance. These findings provide important basic data for future research on hypoxic tolerance in pearl gentian grouper and provide new insights into the interaction between hypoxia and the circadian rhythm in fish. Full article

Objective: To evaluate the association between environmental exposure to the following chemical substances: cadmium (Cd), lead (Pb), nickel (Ni), manganese (Mn), benzene (BZN), and toluene (TLN), and Period Circadian Regulator 3 (PER3) gene variable number of tandem repeats (VNTR) polymorphisms, according to chronotype in a population living in a steel residue-contaminated area. Methods: This assessment comprises a study conducted from 2017 to 2019 with 159 participants who completed health, work, and Pittsburgh sleep scale questionnaires. Cd, Pb, Ni, Mn, BZN, and TLN concentrations in blood and urine were determined by Graphite Furnace Atomic Absorption Spectrometry (GFAAS) and Headspace Gas Chromatography (GC), and genotyping was carried out using Polymerase Chain Reaction (PCR). Results: A total of 47% of the participants were afternoon chronotype, 42% were indifferent, and 11% were morning chronotype. Insomnia and excessive sleepiness were associated with the indifferent chronotype, while higher urinary manganese levels were associated with the morning chronotype (Kruskal–Wallis chi-square = 9.16; p < 0.01). In turn, the evening chronotype was associated with poorer sleep quality, higher lead levels in blood, and BZN and TLN levels in urine (χ² = 11.20; p < 0.01) in non-occupationally exposed individuals (χ² = 6.98; p < 0.01) as well as the highest BZN (χ² = 9.66; p < 0.01) and TLN (χ² = 5.71; p < 0.01) levels detected in residents from the influence zone 2 (far from the slag). Conclusion: Mn, Pb, benzene, and toluene contaminants may have influenced the different chronotypes found in the steel residue-exposed population. Full article

The EARLY MATURITY 8 (EAM8) gene of barley is homologous to the EARLY FLOWERING 3 (ELF3) gene in Arabidopsis, as loss-of-function mutations in this circadian clock gene promote rapid flowering. A previous study demonstrated that the early flowering phenotype of a hulless barley, Lalu, was due to allele eam8.l carrying an alternative splicing mutation in intron 3 that led to intron retention. In the present study, we verified that eam8.l encoded a truncated protein. Although EAM8 was expressed at a higher level in Lalu than in other barley lines with a longer growth period, it did not negatively regulate flowering time. This result further proved that the eam8.l protein was nonfunctional in regulating flowering in barley. The early flowering phenotype of Lalu plants was strongly dependent on the biosynthesis of gibberellin (GA). The eam8.l mutation stopped the suppression of GA biosynthesis, and Lalu accumulated excessive GA, especially in leaves. This was achieved through the upregulated expression of genes in the GA pathway, including GA20ox2, LFY1, SOC1, PAP2, and FPF3. The mutation of the EAM8 gene also abolished the inhibition of FLOWERING LOCUS T-like (FT1) gene expression at night. During the night, expression levels of the FT1 gene were higher than those during the day in Lalu. However, the GA-dependent pathway and FT1 gene mechanism are two independent pathways that promote flowering in Lalu. Alleles of EAM8, therefore, demonstrated an important breeding value in barley, which is probably effective in many other day-length-sensitive crop plants as well; thus, they could be used to tune adaptation in different geographic regions and climatic conditions, a critical issue in times of global warming. Full article

The trigeminal autonomic cephalalgia, cluster headache (CH), is one of the most painful disorders known to man. One of the disorder’s most striking features is the reported diurnal rhythmicity of the attacks. For a majority of patients, the headache attacks occur at approximately the same time every day. Genetic variants of genes involved in the circadian rhythm such as Period Circadian Regulator 1, 2, and 3 (PER1, 2 and 3) are hypothesized to have an effect on the rhythmicity of the attacks. Six PER1, 2 and 3 genetic markers; the indel rs57875989 and five single nucleotide polymorphisms (SNPs), rs2735611, rs2304672, rs934945, rs10462020, and rs228697, were genotyped, using TaqMan^® or regular polymerase chain reaction (PCR), in a Swedish CH case control material. Logistic regression showed no association between CH and any of the six genetic variants; rs57875989, p = 0.523; rs2735611, p = 0.416; rs2304672, p = 0.732; rs934945, p = 0.907; rs10462020, p = 0.726; and rs228697, p = 0.717. Furthermore, no difference in allele frequency was found for patients reporting diurnal rhythmicity of attacks, nor were any of the variants linked to diurnal preference. The results of this study indicate no involvement of these PER genetic variants in CH or diurnal phenotype in Sweden. Full article

Circadian rhythms are ~24 h fluctuations of different biological processes that are regulated by the circadian clock system. They exert a major influence on most of the metabolism, such as the hepatic metabolism. This rhythmicity can be disrupted by obesogenic diets, fact that is considered to be a risk factor for the development of metabolic diseases. Nevertheless, obesogenic diets do not affect both genders in the same manner. We hypothesized that the circadian rhythms disruption of the hepatic metabolism, caused by obesogenic diets, is gender-dependent. Male and female Fischer 344 rats were fed either a standard diet or a cafeteria diet and sacrificed at two different moments, at zeitgeber 3 and 15. Only female rats maintained the circadian variations of the hepatic metabolism under a cafeteria diet. Most of those metabolites were related with the very low density lipoprotein (VLDL) synthesis, such as choline, betaine or phosphatidylcholine. Most of these metabolites were found to be increased at the beginning of the dark period. On the other hand, male animals did not show these time differences. These findings suggest that females might be more protected against the circadian disruption of the hepatic metabolism caused by a cafeteria diet through the increase of the VLDL synthesis at the beginning of the feeding time. Full article

Human studies have shown diurnal rhythms of cholesterol and bile acid synthesis, but a better understanding of the role of the circadian system in cholesterol homeostasis is needed for the development of targeted interventions to improve metabolic health. Therefore, we performed a systematic literature search on the diurnal rhythms of cholesterol synthesis and absorption markers and of bile acid synthesis markers. We also examined the diurnal rhythms of the cholesterol synthesis markers lathosterol and desmosterol, and of the cholesterol absorption markers cholestanol, campesterol, and sitosterol in serum samples from the Bispebjerg study. These samples were collected every three hours over a 24-h period in healthy males (n = 24) who consumed low-fat meals. The systematic search identified sixteen papers that had examined the diurnal rhythms of the cholesterol synthesis markers lathosterol (n = 3), mevalonate (n = 9), squalene (n = 2), or the bile acid synthesis marker 7α-hydroxy-4-cholesten-3-one (C4) (n = 4). Results showed that lathosterol, mevalonate, and squalene had a diurnal rhythm with nocturnal peaks, while C4 had a diurnal rhythm with daytime peaks. Furthermore, cosinor analyses of the serum samples showed a significant diurnal rhythm for lathosterol (cosinor p < 0.001), but not for desmosterol, campesterol, sitosterol, and cholestanol (cosinor p > 0.05). In conclusion, cholesterol synthesis and bile acid synthesis have a diurnal rhythm, though no evidence for a diurnal rhythm of cholesterol absorption was found under highly standardised conditions. More work is needed to further explore the influence of external factors on the diurnal rhythms regulating cholesterol homeostasis. Full article

Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans. Here, we performed the first study to determine how TRF affects gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors in humans. Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm (early TRF (eTRF)) and between 8 am and 8 pm (control schedule). Participants underwent continuous glucose monitoring, and blood was drawn to assess cardiometabolic risk factors, hormones, and gene expression in whole blood cells. Relative to the control schedule, eTRF decreased mean 24-hour glucose levels by 4 ± 1 mg/dl (p = 0.0003) and glycemic excursions by 12 ± 3 mg/dl (p = 0.001). In the morning before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene SIRT1 and the autophagy gene LC3A (all p < 0.04), while in the evening, it tended to increase brain-derived neurotropic factor (BNDF; p = 0.10) and also increased the expression of MTOR (p = 0.007), a major nutrient-sensing protein that regulates cell growth. eTRF also altered the diurnal patterns in cortisol and the expression of several circadian clock genes (p < 0.05). eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans. Full article