Search Results (128)

Background: Colorectal cancer (CRC) is strongly influenced by miRNAs as well as the circadian system. Methods: High-throughput sequencing of miRNAs expressed in the rat colon during 24 h light (L)/dark (D) cycle was performed to identify rhythmically expressed miRNAs. The role of miR-150-5p in CRC progression was analyzed in DLD1 cell line and human CRC tissues. Results: Nearly 10% of mature miRNAs showed a daily rhythm in expression. A peak of miRNAs’ levels was in most cases observed during the first half of the D phase of the LD cycle. The highest amplitude was detected in expression of miR-150-5p and miR-142-3p. In the L phase of the LD cycle, the maximum in miR-30d-5p expression was detected. Gene ontology enrichment analysis revealed that genes interfering with miRNAs with peak expression during the D phase influence apoptosis, angiogenesis, the immune system, and EGF and TGF-beta signaling. Rhythm in miR-150-5p, miR-142-3p, and miR-30d-5p expression was confirmed by real-time PCR. Oncogenes bcl2 and myb and clock gene cry1 were identified as miR-150-5p targets. miR-150-5p administration promoted camptothecin-induced apoptosis. Expression of myb showed a rhythmic profile in DLD1 cells with inverted acrophase with respect to miR-150-5p. miR-150-5p was decreased in cancer compared to adjacent tissue in CRC patients. Decrease in miR-150-5p was age dependent. Older patients with lower expression of miR-150-5p and higher expression of cry1 showed worse survival in comparison with younger patients. Conclusions: miRNA signaling differs between the L and D phases of the LD cycle. miR-150-5p, targeting myb, bcl2, and cry1, can influence CRC progression in a phase-dependent manner. Full article

Alzheimer’s Disease (AD) is the most common type of dementia. The circadian system, which is controlled by the master clock in the Suprachiasmatic Nucleus (SCN) of the hypothalamus, is crucial for various physiological processes. Studies have shown that changes in the circadian rhythms can deteriorate neurodegenerative diseases. Changes in the SCN are associated with cognitive decline in AD. The cognitive impairments in AD, especially memory dysfunctions, may be related to Circadian Rhythm Disturbances (CRDs). Moreover, rhythmic expression of clock genes is disrupted in AD patients. There is a circadian pattern of inflammatory processes in AD, and dysregulation of core clock genes promotes neuroinflammation. The present narrative review addresses the intricate link between CRDs and AD, revisiting the relevant cellular and molecular mechanisms. The association between CRDs and AD highlights the need for further investigation of the underlying mechanisms. Full article

The circadian clock orchestrates behavioral and molecular processes such as eclosion. Understanding eclosion timing may offer insights into circadian mechanisms underlying migratory timing. Here, we characterize the diel and circadian patterns of eclosion and core clock gene expression in the fall armyworm (FAW), Spodoptera frugiperda, a globally distributed migratory moth. Using a custom-designed eclosion monitoring system under 14 h light: 10 h dark (L14: D10) and constant darkness (DD) conditions, we observed robust diel eclosion rhythms peaking shortly after lights-off under L14: D10, which became delayed and damped over three consecutive days in DD. Males showed a tendency toward more dispersed emergence patterns and exhibited statistically distinguishable eclosion distributions from females under both conditions. Expression of five canonical clock genes (cyc, clk, tim, per, cry2) displayed significant 24 h rhythmicity, with generally higher mesors in males. However, sex-specific differences in amplitude and phase were detected only for clk and cyc under L14: D10, not in DD. These findings suggest that sex-specific differences in circadian regulation are limited. Nonetheless, subtle variations in clock gene output and emergence timing in the FAW population established in China may contribute to sex-specific ecological strategies in the novel migratory arena. Full article

Polyembryonic maize, capable of producing multiple seedlings from a single kernel, holds great potential value in agricultural and industrial applications, but the seedling quality needs to be improved. In this study, seedlings of two waxy maize (Zea mays L. sinensis Kulesh) inbred lines, D35 (a polyembryonic line with twin shoots) and N6110 (single-shoot), exhibited similar relative growth rates during 1 to 5 days post-germination. UPLC-MS/MS profiling of 3- to 5-day-old seedling roots and shoots revealed that H2JA, MeSAG, and IAA-Val-Me were the common differentially accumulated metabolites (DAMs) of the 3-day-old vs. 5-day-old seedlings of D35 and N6110 in the same tissues, and MeSAG, tZ9G, cZROG, and DHZROG were identified in D35 vs. N6110 across the same tissues and the same periods. RNA-seq analyses showed various processes involved in seedling development, including DNA replication initiation, rhythmic processes, the cell cycle, secondary metabolic processes, and hormone biosynthetic regulation. The differentially expressed genes (DEGs) between D35 and N6110 were significantly enriched in organic hydroxy compound biosynthetic, alcohol biosynthetic, organic hydroxy compound metabolic, abscisic acid biosynthetic, and apocarotenoid biosynthetic processes. The KEGG-enriched pathways of DAMs and DEGs identified that AUX1, AHP, A-ARR, JAR1, SIMKK, ERF1, and GID2 might be conserved genes regulating seedling growth. The integrated analyses revealed that 98 TFs were potentially associated with multiple hormones, and 24 of them were identified to be core genes, including 11 AP2/ERFs, 4 Dofs, 2 bZIPs, 2 MADS-box genes, 2 MYBs, 1 GATA, 1 LOB, and 1 RWP-RK member. This study promotes a valuable understanding of the complex hormone interactions governing twin-shoot seedling growth and offers potential targets for improving crop establishment via seedling quality. Full article

Green soybean (Glycine max), commonly known as vegetable soybean or edamame, is harvested at reproductive stages 6 to 7 of pod development. At this stage, the seeds are fully grown but still green and not yet mature. Green soybean is a nutritious food high in protein and micronutrients; however, low temperatures negatively impact its production and quality. The mechanisms underlying cold stress in green soybean remain unclear. This study aims to identify differentially expressed genes (DEGs) and key pathways associated with cold tolerance through a comprehensive transcriptomic analysis of cold stress responses in a cold-tolerant green soybean variety at three time points: 3 h, 12 h, and 24 h. We identified 3415 common DEGs across three time points, with significant enrichment in categories such as “rhythmic process”, “response to blue light”, “fatty acid metabolism”, and “fatty acid degradation”. Notably, expression patterns of these pathways were similar after 3 and 24 h of cold exposure. Weighted gene co-expression network analysis (WGCNA) revealed 20 distinct modules, with two principal modules—turquoise and blue—correlating with rhythmic processes and fatty acid pathways. Additionally, we analyzed the genetic regulatory networks within these modules and identified four candidate genes (Glyma.04G015200, Glyma.18G202800, Glyma.02G123700 and Glyma.13G266500) potentially linked to cold tolerance. This study enhances our understanding of the molecular mechanisms of cold stress in green soybean and highlights key cold-responsive genes for further research. Full article

Rhythms, regulated by core clock genes like the period (per) gene family, are crucial for maintaining physiological processes in animals. In teleost fish, including channel catfish (Ictalurus punctatus), these genes have evolved distinct functions. However, the evolutionary characteristics and functional roles of period genes, particularly in response to environmental cues such as feeding, remain unclear. This study aimed to investigate the evolutionary divergence and functional specialization of the period gene family in channel catfish, with a focus on feeding-induced rhythmicity. Four period genes, Ipper1b, Ipper2, Ipper2l, and Ipper3, were identified in channel catfish. Phylogenetic analysis revealed distinct evolutionary paths for these genes, with Ipper2l forming a separate clade from Ipper2. Tissue-specific expression analysis showed differential expression of period genes across tissues, with Ipper1b exhibiting the highest expression in the intestine and Ipper2 being predominantly expressed in the liver. Statistical analysis confirmed significant differences in the expression levels between tissues (p < 0.05), supporting the tissue-specific roles of these genes. Notably, under strict feeding schedules, we observed significant modulation of rhythmic expression in both the brain and liver, with a notable shift in the peak expression times and amplitude changes aligned with the feeding time. These results suggest that feeding serves as a critical Zeitgeber, entraining circadian rhythms in key tissues and potentially enhancing metabolic efficiency. These results demonstrated that feeding schedules play a key role in modulating circadian gene expression in channel catfish. This study provides insights into the evolutionary divergence and functional roles of the period gene family in channel catfish, showing how feeding schedules modulate circadian gene expression in the brain and liver. These findings have potential applications in optimizing feeding strategies for improving fish health and growth in aquaculture. Full article

In mammals, the core molecular clock genes and the overall circadian system are established during early development; during this critical period of development, maternal metabolic condition plays a major role in programming temporal metabolic regulation. Therefore, this study aimed to evaluate the effects of the chronic maternal intake of a high-fat and high-carbohydrate diet (HFCD) before and during pregnancy, in addition to a challenge with HFCD during adulthood, on offspring diurnal metabolic profile and on clock gene expression in central and peripheral circadian oscillators. The HFCD offspring and/or those exposed to the metabolic challenge exhibited alterations in the temporal profiles of analytes associated with both the carbohydrate and lipid metabolisms, as well as markers associated with liver and kidney damage, ranging from phase changes in rhythmicity or, in some cases, to the complete loss of 24 h variations. At the molecular level, the expression of clock genes (Per1, Cry1, Bmal1, and Clock) in the central and peripheral oscillators showed differential susceptibility to undergoing changes in their abundance. Our data indicate that maternal HFCD during pregnancy, a second exposure in adulthood, or both result in the long-term misalignment of the diurnal rhythm’s metabolic and damage markers; these changes are possibly associated with alterations in the core molecular circadian clockwork. Full article

The circadian clock orchestrates photosynthetic and metabolic processes in plants, but the molecular mechanisms underlying the photoperiodic regulation of photosynthetic yield remain poorly understood. Here, we integrated computational modeling and experimental validation to investigate how the skeletal photoperiod modulates photosynthetic efficiency in celery (Apium graveolens L.). Our model revealed that endogenous circadian rhythms dynamically regulate photosynthetic gene expression (e.g., Lhcb1, psbA, RbcS1, and atpA) and photosynthetic parameters (net photosynthetic rate and stomatal conductance) through interactions between clock components (CCA1/LHY and PRR9/PRR7) and light signaling. In particular, the 3L:3D skeleton photoperiod induced the highest 24 h photosynthetic accumulation (a 32% and 22% increase in chlorophyll and nitrogen content, respectively, vs. 12L:12D), outperforming continuous light (LL) and longer photoperiods. Rhythmic peaks of photosynthetic genes aligned with circadian-driven oscillations in the photosynthetic parameters, while a strong negative correlation between the net photosynthetic rate (Pn) and intercellular CO₂ concentration (Ci) emerged under 3L:3D cycles. Model simulations demonstrated robustness in capturing phase-specific gene expression and parameter dynamics across photoperiods, highlighting the role of the circadian clock in optimizing energy use. These results demonstrate that abnormal L/D cycles, particularly 3L:3D, increase photosynthetic yield by enhancing circadian-regulated metabolic coordination, providing a low-energy, high-efficiency strategy for agricultural productivity. This work advances our understanding of photoperiodic manipulation in crop systems and provides a predictive framework for circadian-informed crop management. Full article

The western flower thrips, Frankliniella occidentalis, a worldwide insect pest with its polyphagous feeding behavior and capacity to transmit viruses, follows a diurnal rhythmicity driven by expression of the circadian clock genes. However, it remained unclear how the clock signal triggers the thrips behaviors. This study posed a hypothesis that the clock signal modulates cGMP-dependent protein kinase (PKG) activity to mediate the diurnal behaviors. A PKG gene is encoded in F. occidentalis and exhibits high sequence homologies with those of honeybee and fruit fly. Interestingly, its expression followed a diel pattern with high expression during photophase in larvae and adults of F. occidentalis. It is noteworthy that PKG expression was clearly observed in the midgut during photophase but not in scotophase from our fluorescence in situ hybridization analysis. A prediction of protein–protein interaction suggested its functional association with clock genes. To test this functional link, RNA interference (RNAi) of the PKG gene expression was performed by feeding a gene-specific double-stranded RNA, which led to significant alteration of the two clock genes (Clock and Period) in their expression levels. The RNAi treatment caused adverse effects on early-life development and adult fecundity. To further analyze the role of PKG in affecting diurnal behavior, the adult females were continuously observed for a 24 h period with an automatic digitization device to obtain movement parameters and durations (%) in different micro-areas in the observation arena. Diel difference was observed with speed in RNAi-control females at 0.16 mm/s and 0.08 mm/s, in photo- and scotophase, respectively, whereas diel difference was not observed for the PKG-specific RNAi-treated females, which showed 0.07 mm/s and 0.06 mm/s, respectively. The diel difference was also observed in durations (%) in the control females, more strongly in the intermediate area in the observation arena. Speed and durations in the different micro-areas in mid-scotophase were significantly different from most photophase in the control females, while speed was significantly different mainly during late photophase when comparing effects of control and RNAi treatments in each light phase. Three sequential stages consisting of high activity followed by feeding and visiting of micro-areas were observed for the control females. For RNAi-treated females, the three phases were disturbed with irregular speed and visits to micro-areas. These results suggest that PKG is associated with implementing the diurnal behavior of F. occidentalis by interacting with expressions of the circadian clock genes. Full article

The pseudo response regulator (PRR) gene is an important component of the core oscillator involved in plant circadian rhythms and plays an important role in regulating plant growth and development and stress responses. In this study, we investigated the function of GmPRR7b by overexpression and gene editing approaches. It was found that GmPRR7b plays a role in delaying flowering. While GmPRR7b overexpressing plants showed significantly delayed flowering compared to untransformed WT, GmPRR7b edited plants flowered earlier than the control WT. On the basis of previous research results and bioinformatics analysis, we re-identified 14 soybean PRR genes and analysed their rhythmic expression. Based on the rhythmic expression pattern, we found that GmPRR5/9a and GmPRR5/9b interacted with GmPRR7b by yeast two-hybrid and bimolecular fluorescence complementation (BiFC) experiments. Combined with the expression regulatory networks of the GmPRR7b, we inferred a possible regulatory mechanism by which GmPRR7b affects flowering through quit rhythm expression. These research elements provide valuable references for understanding growth, development, and circadian regulation in soybean. Full article

The paramount objectives of this study were to analyze the beneficial role of the circadian clock in alleviating drought stress in an essential green leafy horticultural crop, spinach (Spinacia oleracea), and to attain knowledge on drought-stress adaptation for crop productivity. From dawn to dusk, a circadian core oscillator-based defense mechanism was noticed in relation to the strength of the chloroplast proteome and transcriptome, and the defense hormone fused it along with the molecular physiology using genotypes “Malav Jyoti” and “Delhi Green”. A photo-periodic rhythmicity containing a 4 h time interval (morning–evening loop) for 12 h in spinach was exhibited under drought-stressed (day-5) and drought re-irrigated (day-10) conditions. The circadian oscillator controlled 70% of the major part of growth and physiological measures such as the biomass, plant height, leaf-relative water content, and the shoot–root ratio under drought stress. Contrarily, drought stress resulted in the upregulation of antioxidative activities and stress markers, whereas it was diversified and maintained in the case of the re-irrigated state at certain rhythmic time intervals of the circadian clock. The physiological parameters we examined, such as net photosynthesis, transpiration, stomatal conductance, and antioxidative enzymes, exhibited the role of the circadian clock in drought stress by showing 80–90% improvements found in plants when they were re-watered after drought stress based on their circadian oscillations. Based on the physiological results, 10 a.m. and 2 p.m. were disclosed to be the rhythmic times for controlling drought stress. Moreover, an extensive study on a gene expression analysis of circadian clock-based genes (CCA1, LHY, TOC1, PRR3, PRR5, PRR7, PRR9, and RVE8) and drought-responsive genes (DREB1, DREB2, and PIP1) depicted the necessity of a circadian oscillator in alleviating drought stress. Hence, the findings of our study allowed for an intense understanding of photo-periodic rhythms in terms of the morning–evening loop, which is in line with the survival rate of spinach plants and occurs by altering cellular ROS-scavenging mechanisms, chloroplast protein profiles, gene regulation, and metabolite concentrations. Full article

Neuroinflammation is involved in the development of depression and may induce depression-like behaviors by affecting metabolism through interactions with circadian rhythms. As the hub of metabolism, mitochondria are regulated by various types of metabolism and release signals that regulate cellular functions. In this study, we performed transcriptomic analysis of the hippocampus of IL-33-overexpressing mice to provide new ideas to explore the pathogenesis of inflammation-mediated depression at the transcriptional level. Male C57BL/6J mice and IL-33-overexpressing mice were subjected to behavioral tests. The hippocampus was extracted during the light or dark period, and differential gene expression analysis was conducted using RNA sequencing. Differential gene enrichment analysis was performed, as well as multilayered analysis of mitochondrial transcriptional rhythms by integrating the regulatory networks and Mito 3.0 database. The results were further verified using RT-qPCR. IL-33-overexpressing mice exhibited depressive behaviors associated with rhythmic disorders and shortened circadian cycles. Differential KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis showed that the top 20 pathways with the lowest p-values included mood-related, immune-related, and circadian rhythm-related pathways. Differential gene GO (Gene Ontology) enrichment analysis showed that 20 of the top 30 pathways with the lowest p-values were related to metabolism. Transcriptome data from IL-33-overexpressing mice showed that the mitochondrial-encoded subunit of the oxidative respiratory complex showed predominantly increased expression during the light period. Metabolic disorders and disrupted mitochondrial transcriptional rhythm were also observed. Weighted gene correlation network analysis showed that the circadian cycle is associated with depression-like behavior disorders. Network analysis showed that circadian-related genes were enriched in mitochondrial pathways related to metabolism and oxidative phosphorylation. Multilayer analysis of mitochondrial transcriptional rhythms using the mitochondrial database Mito 3.0 revealed that mitochondrial dynamics and surveillance pathways were the most enriched. The depressive behavior in mice caused by long-term IL-33 stimulation may be related to changes in the transcriptional rhythms of metabolism-related genes and the interaction between mitochondria and clock genes. This suggests that mitochondrial transcriptional rhythms are central to the pathogenesis of microinflammation-induced depression, further supporting the potential of mitochondria as a target for the prevention and treatment of depression. Full article

The heading date is one of the important traits in rice, which greatly affects grain yield and regional adaptability. Although the flowering pathways in rice have been extensively investigated, the genes involved in flowering remain largely unknown. Here, we report a rice lhd mutant, which showed late flowering under both long-day (LD) and short-day (SD) conditions. Through MutMap+ and linkage analysis, a deletion mutation in OsMetAP10 was inferred as the most likely candidate for lhd late flowering. OsMetAP10 encodes a methionine aminopeptidase that belongs to the peptidase_M24 subfamily III. The OsMetAP10 gene is constitutively expressed in rice and is induced by light, with a rhythmic expression pattern. OsMetAP10 knockout lines displayed late heading as the lhd mutation, while no alternations in morphology and heading were observed on OsMetAP10 overexpression lines, further confirming the mutation of OsMetAP10 as responsible for the late heading of lhd. Through RT-qPCR and transcriptome analysis, we revealed that the upregulated expression of the FT-like gene OsFLT4, a negatively flowering regulator, and the downregulation of flower development-related genes, OsMADS14, OsMADS15, and OsMADS34, played critical roles in determining the late flowering of the OsMetAP10 mutation. This study reports a new gene affecting flowering and provides a new insight into the role of OsMetAP10 in regulating rice heading. Full article

Background: ATP-binding cassette (ABC) transporters are expressed in the vascular walls of brain capillaries and remove toxic chemicals from the brain. The expression of ABC transporters in peripheral organs is transcriptionally regulated by clock genes and exhibits 24 h periodic fluctuations. In addition, clock gene outputs diminish with aging. In this study, we evaluated whether the expression of ABC transporters in the blood–brain barrier (BBB) of young mice had a 24 h cycle, and whether the expression of ABC transporters in the BBB decreased with age. Methods: Brain microvascular (BMV) fractions from the cerebral cortex of male C57BL/6J mice were prepared using dextran. BMV fractions from young mice (12 weeks old) were prepared every four hours to evaluate 24 h rhythmicity. BMV fractions from both young and aged mice (85 weeks old) were prepared when protein expression peaked (Zeitgeber Time 5). Protein and mRNA expression of ABC transporters in BMV fractions were measured. Results: In young mice, protein expression of P-glycoprotein, breast cancer resistance protein, and multidrug resistance protein 4 showed time-dependent variations with a peak in the light phase (Zeitgeber Time 5); mRNA expression showed no time-dependent variation. The protein expression of these transporters was lower in the BBB of aged mice than in that of young mice, although mRNA expression did not differ between young and aged mice. Conclusions: ABC transporter protein expression levels in BMV endothelial cells decreased with aging; however, mRNA levels did not change, which suggests changes in protein expression did not result from diminished clock gene output. Further studies are needed to elucidate the mechanisms by which ABC transporter expression in the BBB decreases with aging. Full article

Melatonin is involved in various functions such as the timing of circadian rhythms, energy metabolism, and body mass gain in experimental animals. However, its effects on adipose tissue lipid metabolism are still unclear. This study analyzes the effects of melatonin on the relative gene expression of lipolytic proteins in rat mesenteric adipose tissue and free fatty acid (FFA) and glycerol plasma levels of male Wistar rats fed a high-fat (HFD) or maintenance diet. Four experimental groups were established: control, obese, and control or obese plus 2.3 mg/kg/day of melatonin in tap water. After 11 weeks, animals were sacrificed at different times throughout a 24 h cycle, and mesenteric adipose tissue and plasma samples were collected and analyzed. Cgi58, Perilipin, and Dgat1 gene expression, as well as FFA and glycerol concentrations, showed rhythm patterns in the control group. HFD disrupted those rhythm patterns and increased FFA and glycerol concentrations during the dark photoperiod. In both melatonin-treated groups, almost all analyzed genes showed circadian patterns. Notably, melatonin significantly prevented the increase in FFA levels during the dark photoperiod in obese rats (obese group: ~1100 mM vs. obese + melatonin group: ~600 μM, similar to control levels). However, the rhythmic pattern observed in control animals was not sustained. According to our results, melatonin could regulate circadian gene transcription of mesenteric adipose tissue lipolysis proteins. The effect of melatonin on preventing elevated FFA plasma levels associated with high-fat diet intake warrants further investigation. Full article