Search Results (1,550)

Chronotypes play a crucial role in regulating sleep–wake cycles and overall health. The aim of this study was to investigate chronotype, sleep quality, polymorphisms of clock genes and the level of leptin in serum. We used standardized questionnaires to assess chronotype and sleep quality. Genetic analysis was performed to determine the selected clock gene polymorphism. Serum leptin level was measured by the Elisa method. The results showed that serum leptin concentration was elevated in women, as well as in men who had a high waist-to-hip ratio (WHR) and body mass index (BMI). The evidence indicated that younger students (<22 years old) were most likely to experience poor sleep quality. Nevertheless, our multivariate analysis revealed that young age and a morning-oriented chronotype were associated with better sleep quality. We noted that clock gene polymorphisms were present in 28.6% of the participants. Moreover, polymorphisms of PER1 c.2247C>T (rs2735611) and PER2 c.-12C>G (rs2304672) genes were associated with serum leptin level and chronotype, respectively. These findings provide insights into the relationships between chronotype, sleep quality, clock gene polymorphisms and obesity risk in biomedical students. Understanding these factors can contribute to better sleep management and potential interventions to improve health outcomes in humans. Full article

Circadian rhythms, the internal timekeeping systems governing physiological processes, significantly influence skin health, particularly in response to ultraviolet radiation (UVR). Disruptions in circadian rhythms can exacerbate UVR-induced skin damage and increase the risk of skin aging and cancer. This review explores how circadian rhythms affect various aspects of skin physiology and pathology, with a special focus on DNA repair. Circadian regulation ensures optimal DNA repair following UVR-induced damage, reducing mutation accumulation, and enhancing genomic stability. The circadian control over cell proliferation and apoptosis further contributes to skin regeneration and response to UVR. Oxidative stress management is another critical area where circadian rhythms exert influence. Key circadian genes like brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) modulate the activity of antioxidant enzymes and signaling pathways to protect cells from oxidative stress. Circadian rhythms also affect inflammatory and immune responses by modulating the inflammatory response and the activity of Langerhans cells and other immune cells in the skin. In summary, circadian rhythms form a complex defense network that manages UVR-induced damage through the precise regulation of DNA damage repair, cell proliferation, apoptosis, inflammatory response, oxidative stress, and hormonal signaling. Understanding these mechanisms provides insights into developing targeted skin protection and improving skin cancer prevention. Full article

Time-restricted eating (TRE) is a circadian rhythm-based intermittent fasting intervention that has been used to treat obesity. However, the efficacy and safety of TRE for fat loss have not been comprehensively examined and the influences of TRE characteristics on such effects are unknown. This systematic review and meta-analysis comprehensively characterized the efficacy and safety of TRE for fat loss in adults with overweight and obese, and it explored the influence of TRE characteristics on this effect. Methods: A search strategy based on the PICOS principle was used to find relevant publications in seven databases. The outcomes were body composition, anthropometric indicators, and blood lipid metrics. Twenty publications (20 studies) with 1288 participants, covering the period from 2020 to 2024, were included. Results: Compared to the control group, TRE safely and significantly reduced body fat percentage, fat mass, lean mass, body mass, BMI, and waist circumference (MDpooled = −2.14 cm, 95% CI = −2.88~−1.40, p < 0.001), and increased low-density lipoprotein (LDL) (MDpooled = 2.70, 95% CI = 0.17~5.22, p = 0.037), but it did not alter the total cholesterol, high-density lipoprotein, and triglycerides (MDpooled = −1.09~1.20 mg/dL, 95% CI −4.31~5.47, p > 0.05). Subgroup analyses showed that TRE only or TRE-caloric restriction with an eating window of 6 to 8 h may be appropriate for losing body fat and overall weight. Conclusions: This work provides moderate to high evidence that TRE is a promising dietary strategy for fat loss. Although it may potentially reduce lean mass and increase LDL, these effects do not pose significant safety concerns. This trial was registered with PROSPERO as CRD42023406329. Full article

This article proposes a methodology for establishing a relationship between the change rate of a given gene (relative to a given taxon) together with the amino acid composition of the proteins encoded by this gene and the traits of the species containing this gene. The methodology is illustrated based on the mammalian genes responsible for regulating the circadian rhythms that underlie a number of human disorders, particularly those associated with aging. The methods used are statistical and bioinformatic ones. A systematic search for orthologues, pseudogenes, and gene losses was performed using our previously developed methods. It is demonstrated that the least conserved Fbxl21 gene in the Euarchontoglires superorder exhibits a statistically significant connection of genomic characteristics (the median of dN/dS for a gene relative to all the other orthologous genes of a taxon, as well as the preference or avoidance of certain amino acids in its protein) with species-specific lifespan and body weight. In contrast, no such connection is observed for Fbxl21 in the Laurasiatheria superorder. This study goes beyond the protein-coding genes, since the accumulation of amino acid substitutions in the course of evolution leads to pseudogenization and even gene loss, although the relationship between the genomic characteristics and the species traits is still preserved. The proposed methodology is illustrated using the examples of circadian rhythm genes and proteins in placental mammals, e.g., longevity is connected with the rate of Fbxl21 gene change, pseudogenization or gene loss, and specific amino acid substitutions (e.g., asparagine at the 19th position of the CRY-binding domain) in the protein encoded by this gene. Full article

Melatonin (5-methoxy-N-acetyltryptamine) is an indoleamine compound that plays a critical role in the regulation of circadian rhythms. While melatonin is primarily synthesized from the amino acid tryptophan in the pineal gland of the brain, it can also be produced locally in various tissues, such as the skin and intestines. Melatonin’s effects in target tissues can be mediated through receptor-dependent mechanisms. Additionally, melatonin exerts various actions via receptor-independent pathways. In biological systems, melatonin and its endogenous metabolites often produce similar effects. While injuries are common in daily life, promoting optimal wound healing is essential for patient well-being and healthcare outcomes. Beyond regulating circadian rhythms as a neuroendocrine hormone, melatonin may enhance wound healing through (1) potent antioxidant properties, (2) anti-inflammatory actions, (3) infection control, (4) regulation of vascular reactivity and angiogenesis, (5) analgesic (pain-relieving) effects, and (6) anti-pruritic (anti-itch) effects. This review aims to provide a comprehensive overview of scientific studies that demonstrate melatonin’s potential roles in supporting effective wound healing. Full article

This study addressed the following questions: How does continuous lighting (CL) impact plant physiology, and photosynthetic and stress responses? Does the impact of CL depend on the source of the light and other environmental factors (natural vs. artificial)? Do responses to CL differ for native and non-native plant species in the subarctic region and, if differences exist, what physiological reasons might they be associated with them? Experiments were conducted with three plants native to the subarctic region (Geranium sylvaticum L., Geum rivale L., Potentilla erecta (L.) Raeusch.) and three non-native plant species (Geranium himalayense Klotzsch, Geum coccineum Sibth. and Sm., Potentilla atrosanguinea Loddiges ex D. Don) introduced in the Polar-Alpine Botanic Garden (KPABG, 67°38′ N). The experimental groups included three species pairs exposed to (1) a natural 16 h photoperiod, (2) natural CL, (3) an artificial 16 h photoperiod and (4) artificial CL. In the natural environment, measurements of physiological and biochemical parameters were carried out at the peak of the polar day (at the end of June), when the plants were illuminated continuously, and in the second week of August, when the day length was about 16 h. Th experiments with artificial lighting were conducted in climate chambers where plants were exposed to 16 h or 24 h photoperiods for two weeks. Other parameters (light intensity, spectrum composition, temperature and air humidity) were held constant. The obtained results have shown that plants lack specific mechanisms of tolerance to CL. The protective responses are non-specific and induced by developing photo-oxidative stress. In climate chambers, under constant environmental conditions artificial CL causes leaf injuries due to oxidative stress, the main cause of which is circadian asynchrony. In nature, plants are not photodamaged during the polar day, as endogenous rhythms are maintained due to daily fluctuations of several environmental factors (light intensity, spectral distribution, temperature and air humidity). The obtained data show that among possible non-specific protective mechanisms, plants use flavonoids to neutralize the excess ROS generated under CL. In local subarctic plants, their photoprotective role is significantly higher than in non-native introduced plant species. Full article

Introduction: According to current knowledge, at birth, the pineal gland and melatonin receptors are already present and the suprachiasmatic nucleus is largely functional, and noradrenaline, the key pineal transmitter, can be detected in the early foetal period. It is still unclear why the pineal gland is not able to start its own pulsatile synthesis and secretion of melatonin in the first months of life, and as a result, infants during this time are dependent on an external supply of melatonin. Method: The causes and consequences of this physiological melatonin deficiency in human infancy are examined in a systematic review of the literature, in which 40 of 115 initially selected publications were evaluated in detail. The references of these studies were checked for relevant studies on this topic. References from previous reviews by the author were taken into account. Results: The development and differentiation of the pineal gland, the pinealocytes, as the site of melatonin synthesis, and the development and synaptic coupling of the associated predominantly noradrenergic neural pathways and vessels and the associated Lhx4 homebox only occurs during the first year of life. Discussion: The resulting physiological melatonin deficiency is associated with sleep disorders, infant colic, and increased crying in babies. Intervention studies indicate that this deficiency should be compensated for through breastfeeding, the administration of nonpooled donor milk, or through industrially produced chrononutrition made from nonpooled cow’s milk with melatonin-poor day milk and melatonin-rich night milk. Full article

Deprivation of sleep (DS) and its effects on circadian rhythm gene expression are not well understood despite their influence on various physiological and psychological processes. This study aimed to elucidate the changes in the expression of circadian rhythm genes following a night of sleep and DS. Their correlation with sleep architecture and physical activity was also examined. The study included 81 participants who underwent polysomnography (PSG) and DS with actigraphy. Blood samples were collected after PSG and DS. Expression levels of brain and muscle ARNT-like 1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), neuronal PAS domain protein 2 (NPAS2), period 1 (PER1), cryptochrome 1 (CRY1) and nuclear receptor subfamily 1 group D member 1 (NR1D1) were analyzed using qRT-PCR. DS decreased the expression of CLOCK and BMAL1 while increasing PER1. PER1 expression correlated positively with total sleep time and non-rapid-eye-movement (NREM) sleep duration and negatively with sleep latency, alpha, beta and delta waves in the O1A2 lead. Physical activity during DS showed positive correlations with CLOCK, BMAL1, and CRY1. The findings highlight the role of PER1 in modulating sleep patterns, suggesting potential targets for managing sleep-related disorders. Further research is essential to deepen the understanding of these relationships and their implications. Full article

The regulation of the mammalian circadian clock is largely dependent on heredity. In model animals for circadian rhythm studies, C57BL/6 and BALB/c mice exhibit considerable differences in their adaptation to circadian disruption, yet deeper comparisons remain unexplored. Here, we have established embryonic fibroblast cells derived from C57BL/6 mice (MEF) and BALB/c (BALB/3T3) mice, which have been transfected with the Bmal1 promoter-driven luciferase (Bmal1-Luc) reporter gene. Next, dexamethasone was applied for various cyclic stimulations, which revealed that Bmal1 bioluminescence of MEF cells was entrained to 24 to 26 h cycles, whereas BALB/3T3 cells have a wider range (22 to 28 h) with lower amplitudes. Behaviorally, BALB/c mice swiftly adapted to a 6-h advance light/dark cycle, unlike C57BL/6 mice. Furthermore, we found the expression of the circadian rhythm gene Npas2 in BALB/c mice is significantly lower than that in C57BL/6 mice. This observation is consistent with the differentially expressed genes (DEGs) in the intestine and lung tissues of C57BL/6 and BALB/c mice, based on the RNA-seq datasets downloaded from the Gene Expression Omnibus (GEO). In summary, our study uncovers that BALB/c mice possess greater resilience in circadian rhythm than C57BL/6 mice, both cellular and behaviorally, identifying potential genes underlying this difference. Full article

Background: Chronic liver diseases such as hepatic tumors can affect the brain through the liver–brain axis, leading to neurotransmitter dysregulation and behavioral changes. Cancer patients suffer from fatigue, which can be associated with sleep disturbances. Sleep is regulated via two interlocked mechanisms: homeostatic regulation and the circadian system. In mammals, the hypothalamic suprachiasmatic nucleus (SCN) is the key component of the circadian system. It generates circadian rhythms in physiology and behavior and controls their entrainment to the surrounding light/dark cycle. Neuron–glia interactions are crucial for the functional integrity of the SCN. Under pathological conditions, oxidative stress can compromise these interactions and thus circadian timekeeping and entrainment. To date, little is known about the impact of peripheral pathologies such as hepatocellular carcinoma (HCC) on SCN. Materials and Methods: In this study, HCC was induced in adult male mice. The key neuropeptides (vasoactive intestinal peptide: VIP, arginine vasopressin: AVP), an essential component of the molecular clockwork (Bmal1), markers for activity of neurons (c-Fos), astrocytes (GFAP), microglia (IBA1), as well as oxidative stress (8-OHdG) in the SCN were analyzed by immunohistochemistry at four different time points in HCC-bearing compared to control mice. Results: The immunoreactions for VIP, Bmal1, GFAP, IBA1, and 8-OHdG were increased in HCC mice compared to control mice, especially during the activity phase. In contrast, c-Fos was decreased in HCC mice, especially during the late inactive phase. Conclusions: Our data suggest that HCC affects the circadian system at the level of SCN. This involves an alteration of neuropeptides, neuronal activity, Bmal1, activation of glia cells, and oxidative stress in the SCN. Full article

In the search for Alzheimer’s disease (AD) therapies, most animal models focus on familial AD, which accounts for a small fraction of cases. The majority of AD cases arise from stress factors, such as oxidative stress, leading to neurological changes (sporadic AD). Early in AD progression, dysfunction in γ-secretase causes the formation of insoluble Aβ_1-42 peptides, which aggregate into senile plaques, triggering neurodegeneration, cognitive decline, and circadian rhythm disturbances. To better model sporadic AD, we used a new AD rat model induced by intracerebroventricular administration of Aβ_1-42 oligomers (icvAβ_1-42) combined with melatonin deficiency via pinealectomy (pin). We validated this model by assessing spatial memory using the radial arm maze test and measuring Aβ_1-42 and γ-secretase levels in the frontal cortex and hippocampus with ELISA. The icvAβ_1-42 + pin model experienced impaired spatial memory and increased Aβ_1-42 and γ-secretase levels in the frontal cortex and hippocampus, effects not seen with either icvAβ_1-42 or the pin alone. Chronic melatonin treatment reversed memory deficits and reduced Aβ_1-42 and γ-secretase levels in both structures. Our findings suggest that our icvAβ_1-42 + pin model is extremely valuable for future AD research. Full article

Background. Transsphenoidal surgery is the treatment of choice for Cushing’s disease. Successful surgery is associated with subnormal postoperative serum cortisol concentrations and cortisoluria levels, which may guide decisions regarding immediate reoperation. Remission is defined as the biochemical reversal of hypercortisolism with the re-emergence of diurnal circadian rhythm. Methods. A single-center prospective cohort study was conducted among thirty-three patients who underwent transsphenoidal pituitary surgery for Cushing’s disease. Postoperative surgical outcomes, daily morning cortisolemia, and 24 h urinary-free cortisol from the first to the fifth morning were evaluated. Results. All patients underwent surgery, with a remission rate of 81.2%. Of the 26 patients who achieved early remission, 92% remained in remission. Two patients (7.7%) showed recurrence of Cushing’s disease during a mean follow-up of 81.7 months. Early postoperative hypocortisolism suggests complete removal of the tumor, correlating with high rates of remission (p < 0.001). Also, in 12.5% of patients with early cortisol values >138 nmol/L, there was a gradual late remission. Conclusions. In our cohort of patients, the endoscopic transsphenoidal approach was safe and effective in the treatment of Cushing’s disease. We demonstrated that serum and urinary cortisol concentrations did not experience significant fluctuations from the first to the fifth day. This constitutes an accurate predictor of durable remission, comprising a distinctive finding in the intermediate term by our team. Full article

Housing conditions are essential for ensuring animal welfare and high-quality research outcomes. In this study, we continuously monitored air quality—specifically ammonia, carbon dioxide, relative humidity, and temperature—in Individually Ventilated Cages (IVCs) housing five female or male C57BL/6N mice. The cages were cleaned either weekly or bi-weekly, and the data were collected as the mice aged from 100 to 348 days. The survival rate remained above 96%, with body weight increasing by 35–52% during the study period. The ammonia levels rose throughout the cleaning cycle, but averaged below 25 ppm. However, in the older, heavier mice with bi-weekly cage cleaning, the ammonia levels reached between 25 and 75 ppm, particularly in the males. While circadian rhythms influenced the ammonia concentration only to a small extent, the carbon dioxide levels varied between 800 and 3000 ppm, increasing by 30–50% at night and by 1000 ppm with body weight. Humidity also correlated primarily with the circadian rhythms (10% higher at night) and, to a lesser extent, with body weight, reaching ≥70% in the middle-aged mice. The temperature variations remained minimal, within a 1 °C range. We conclude that air quality assessments in IVCs should be conducted during animals’ active periods, and both housing density and biomass must be considered to optimise welfare. Full article

Sexual maturation in goats is a dynamic process regulated precisely by the hypothalamic–pituitary–gonadal axis and is essential for reproduction. The hypothalamus plays a crucial role in this process and is the control center of the reproductive activity. It is significant to study the molecular mechanisms in the hypothalamus regulating sexual maturation in goats. We analyzed the serum hormone profiles and hypothalamic mRNA expression profiles of female goats during sexual development (1 day old (neonatal, D1, n = 5), 2 months old (prepuberty, M2, n = 5), 4 months old (sexual maturity, M4, n = 5), and 6 months old (breeding period, M6, n = 5)). The results indicated that from D1 to M6, serum hormone levels, including FSH, LH, progesterone, estradiol, IGF1, and leptin, exhibited an initial increase followed by a decline, peaking at M4. Furthermore, we identified a total of 508 differentially expressed genes in the hypothalamus, with a total of four distinct expression patterns. Nuclear receptor subfamily 1, group D, member 1 (NR1D1), glucagon-like peptide 1 receptor (GLP1R), and gonadotropin-releasing hormone 1 (GnRH-1) may contribute to hormone secretion, energy metabolism, and signal transduction during goat sexual maturation via circadian rhythm regulation, ECM receptor interactions, neuroactive ligand–receptor interactions, and Wnt signaling pathways. This investigation offers novel insights into the molecular mechanisms governing the hypothalamic regulation of goat sexual maturation. Full article

Cystic fibrosis (CF) is a monogenic syndrome caused by variants in the CF Transmembrane Conductance Regulator (CFTR) gene, affecting various organ and systems, in particular the lung, pancreas, sweat glands, liver, gastrointestinal tract, vas deferens, and vascular system. While for some organs, e.g., the pancreas, a strict genotype-phenotype occurs, others, such as the lung, display a different pathophysiologic outcome in the presence of the same mutational asset, arguing for genetic and environmental modifiers influencing severity and clinical trajectory. CFTR variants trigger a pathophysiological cascade of events responsible for chronic inflammatory responses, many aspects of which, especially related to immunity, are not ascertained yet. Although clock genes expression and function are known modulators of the innate and adaptive immunity, their involvement in CF has been only observed in relation to sleep abnormalities. The aim of this review is to present current evidence on the clock genes role in immune-inflammatory responses at the lung level. While information on this topic is known in other chronic airway diseases (chronic obstructive pulmonary disease and asthma), CF lung disease (CFLD) is lacking in this knowledge. We will present the bidirectional effect between clock genes and inflammatory factors that could possibly be implicated in the CFLD. It must be stressed that besides sleep disturbance and its mechanisms, there are not studies directly addressing the exact nature of clock genes’ involvement in inflammation and immunity in CF, pointing out the directions of new and deepened studies in this monogenic affection. Importantly, clock genes have been found to be druggable by means of genetic tools or pharmacological agents, and this could have therapeutic implications in CFLD. Full article