Search Results (209)

Long-term excessive fluoride intake from food causes skeletal fluorosis, which manifests as bone sclerosis, deformation, joint dysfunction, and even disability. Mitophagy and ion homeostasis regulate bone function. This study investigated the role of melatonin (MLT) in mitigating this condition, given its known involvement in bone remodeling and the fact that fluoride impairs its synthesis in the pineal gland. Firstly, network pharmacology and molecular docking identified mitophagy as MLT’s key pathway against sodium fluoride (NaF)-induced osteosclerosis. Subsequently, a 400 mg/kg/day body weight NaF exposure model in chicken model with 25 mg/kg/day body weight MLT intervention were established in the current study. Fluoride exposure caused the disturbance of ion homeostasis, and the impairment of mitochondria and activation of PTEN-induced putative kinase1 (PINK1)/E3 ubiquitin ligase Park2 (Parkin)-mediated mitophagy in the bone. Importantly, these deleterious effects were significantly restored by MLT supplementation. In conclusion, NaF causes bone injury via ion homeostasis disruption, osteoblast mitochondrial damage, leading to excessive mitophagy. MLT inhibits fluoride-induced mitophagy through the calcium ion flow-mediated PINK1/Parkin pathway, mitigating bone damage. This study can not only ensure the safety of animal-derived food but also provide a theoretical basis for the prevention and treatment of fluorosis in humans and animals. Full article

The pineal gland is a key component of the avian circadian system, responsible for melatonin (MLT) secretion that reflects and regulates daily rhythmicity. While the post-hatching turkey is known for its highly sensitive and efficient pineal system, the functional development of this gland during embryogenesis has not been described. To determine the measurable onset and regulation of MLT secretion, pineal glands from turkey embryos aged 22, 24, and 26 days (ED 22–26) were incubated in a superfusion culture under various light conditions and with or without norepinephrine (NE). MLT concentrations in the medium were measured by radioimmunoassay. Under the experimental conditions, MLT secretion was first reliably measurable at ED 22 and increased thereafter toward hatching. Under a 12L:12D cycle, pinealocytes exhibited a stable circadian rhythm with a fourfold amplitude between night and day. The glands adapted to a reversed light–dark cycle and responded strongly to a 3 h nocturnal light pulse with a 30% decrease in MLT levels. Rhythmic MLT secretion persisted under constant light or darkness, indicating an active endogenous oscillator. NE markedly suppressed MLT secretion in all embryos, confirming the early development of adrenergic regulation. Thus, by ED 22 the embryonic turkey pineal exhibits photosensitivity, endogenous rhythmicity, and NE responsiveness, although secretion at earlier stages cannot be excluded due to detection limits. These results fill a gap in understanding avian pineal ontogeny and establish the turkey embryo as a good model for studying the early development of circadian regulation in birds. Full article

In birds, light can penetrate the cranial bones and reach deep brain regions, where non-visual photoreceptors, especially in the hypothalamus, detect spectral and photoperiodic cues. Alongside retinal photoreception, deep-brain light sensing contributes to circadian entrainment and regulates melatonin secretion by the pineal gland. These light-driven pathways modulate endocrine activity, playing a key role in muscle development. This review explores how monochromatic light-emitting diode (LED) illumination, particularly green and blue wavelengths, affects the somatotropic axis (growth hormone-releasing hormone [GHRH]-growth hormone [GH]-insulin-like growth factor 1 [IGF-1]), the gonadal axis (gonadotropin-releasing hormone [GnRH]-luteinizing hormone [LH]/follicle-stimulating hormone [FSH]-sex steroids [testosterone, estrogen, progesterone]), the thyroid axis (thyrotropin-releasing hormone [TRH]-thyroid-stimulating hormone [TSH]-thyroxine [T₄]/triiodothyronine [T₃]), and the hypothalamic-pituitary-adrenal (HPA) axis (corticotropin-releasing hormone [CRH]-adrenocorticotropic hormone [ACTH]-corticosterone). Green light enhances early-stage muscle growth via GHRH and IGF-1 upregulation, while blue light supports later myogenic activity and oxidative balance. Light schedules also influence melatonin dynamics, which in turn modulate endocrine axis responsiveness to photic cues. Furthermore, variations in photoperiod and exposure to artificial lights at night (ALAN) affect thyroid activity and HPA axis reactivity, influencing metabolism, thermoregulation, and stress resilience. Together, ocular and intracranial photoreception form a complex network that links environmental light to hormonal regulation and muscle growth. These insights support the strategic use of LED lighting to optimize broiler performance and welfare. Full article

Background/Objectives: Melatonin, produced by the placenta and pineal gland, regulates circadian timing and has antioxidant and immunomodulatory actions. After birth, neonatal secretion is low and its circadian pattern matures over months; evidence in preterm neonates is mixed. We longitudinally monitored morning blood melatonin from birth to 38 weeks’ postmenstrual age (PMA) in breast milk-fed preterm neonates, assessing differences by time of birth (day vs. night), PMA, and weight-for-gestational-age (WfGA). Methods: A prospective NICU cohort, conducted within the ProMote study. In total, 132 preterm neonates were recruited from 112 mothers. For infants ≥33 weeks’ GA, three samples were obtained: umbilical cord (available in 94; otherwise at the first NICU admission), day of life (DOL) 4–7, and DOL 10–14; for infants <33 weeks’ GA, an additional sample at 35–36 weeks’ PMA. Melatonin was measured by ELISA. Primary analyses used raw melatonin concentrations in linear mixed-effects models; sensitivity analyses checked robustness. Results: A final sample comprised 122 neonates. Concentrations were low to modest with wide between-neonate variation and no monotonic change across PMA. Mixed models showed no consistent differences by time of birth and no stable WfGA effect; occasional PMA-specific contrasts did not recur at adjacent time points. Umbilical cord concentrations were low, and gestational age at birth did not materially influence levels at a given PMA. Sensitivity analyses led to the same inference. Conclusions: In breast milk-fed preterm neonates, morning serum melatonin from 26–38 weeks’ PMA shows substantial individual variability without consistent differences by time of birth, PMA, or WfGA. Full article

Background and Objectives: The pineal gland is a neuroendocrine structure whose function can be disrupted in patients with malignancies. This study examines the differences in pineal gland volume between oncology patients and healthy controls, as well as the relationship between volume and the duration of chemotherapy. Materials and Methods: A retrospective study included 400 participants, divided into two groups: 200 oncology patients and 200 healthy controls. The pineal gland volume was measured using MRI scans, utilizing T1-sagittal, T2-coronal/axial sections, and post-contrast 3D T1W MPRAGE tomograms. The volume was calculated based on the ellipse approximation formula: V = (L × H × W)/2. The study analyzed the relationships between pineal gland volume and factors such as age, sex, primary tumor origin, and the duration of chemotherapy. Results: The pineal gland volume was significantly smaller in oncology patients in comparison with the healthy controls (p < 0.001). The average volume in oncology patients was 32.41 ± 16.79 mm³, whereas in healthy controls, it was 59.26 ± 29.99 mm³. A significantly smaller pineal gland volume was observed in patients with malignancies, regardless of sex, with no notable differences between groups. Age also did not significantly influence gland volume (p > 0.05). The primary tumor site did not significantly influence gland volume (p > 0.05). A moderate positive correlation was observed between the duration of chemotherapy and pineal gland volume (ρ = 0.322; p = 0.007). Conclusions: The pineal gland showed reduced volume in oncology patients compared to controls. The observed positive correlation with chemotherapy duration should be interpreted cautiously and may reflect survivorship bias rather than direct treatment effects. Full article

Many experimental and clinical studies published so far demonstrate that melatonin—produced mainly by the pineal gland located deep in the middle of the brain, between the two cerebral hemispheres, and in smaller quantities in a number of other organs and cells of the body—can be successfully used to treat different types of human female infertility. To accomplish this, melatonin acts mainly on the ovary, the uterus, and the preimplantation embryo, through its antioxidant, anti-inflammatory, and immunomodulatory effects, in addition to acting as a hormone and cytokine modulator. In particular, it increases oocyte developmental competence and uterine receptivity for the implanting embryo, improves placental health and function, prevents immune rejection of the implanting embryo and spontaneous pregnancy loss, and alleviates symptoms of endometriosis and adenomyosis. Yet, the use of melatonin in these contexts remains relatively limited, despite its convincing safety profile. This may be partly due to the fact that pertinent data concerning the use of melatonin in female infertility treatment are dispersed across various specialized scientific and medical journals, making it difficult for doctors and embryologists confronted with female infertility issues to access all of them. Therefore, this article was written to provide data that are easily understood. It draws from recent findings collected from different specialized journals focused on the molecular mechanisms of action, the clinical data, and the safety of this multifaceted biomolecule in the treatment of female infertility. Full article

Background/Objectives: 1,8-Cineole, an epoxy monoterpene, is a key volatile component of Sugmel-3, a traditional Mongolian medicine used for treating insomnia. Although previous studies suggest that 1,8-Cineole can cross the blood–brain barrier (BBB), its precise spatiotemporal distribution in the brain and its in situ association with alterations in neurotransmitter (NT) levels remain unclear. This study utilized ambient mass spectrometry imaging (AFADESI-MSI) to investigate the dynamic brain distribution of 1,8-Cineole and its major metabolite, as well as their correlation with NT levels. Methods: Sprague Dawley rats (n = 3 per time point) received oral administration of 1,8-Cineole (65 mg/kg). Brain tissues were harvested 5 min, 30 min, 3 h, and 6 h post dose and analyzed using AFADESI-MSI. The spatial and temporal distributions of 1,8-Cineole, its metabolite 2-hydroxy-1,8-Cineole, key neurotransmitters (e.g., 5-HT, GABA, glutamine, melatonin), and related endogenous metabolites were mapped across 13 functionally distinct brain microregions. Results: AFADESI-MSI demonstrated rapid brain entry of 1,8-Cineole and its metabolite, with distinct spatiotemporal pharmacokinetics. The metabolite exhibited higher brain exposure, with 1,8-Cineole predominant in the cortex (CTX) and hippocampus (HP), while its metabolite showed pronounced accumulation in the pineal gland (PG), alongside CTX/HP. Region-dependent alterations in neurotransmitter levels (notably in PG, HP) correlated with drug concentrations, with observed increases in key molecules of the serotonergic and GABAergic pathways. Conclusions: Using AFADESI-MSI, this study provides the first spatiotemporal map of 1,8-Cineole and its metabolite in the brain. The correlation between their region-specific distribution and local neurotransmitter alterations suggests a direct mechanistic link to Sugmel-3′s sedative–hypnotic efficacy, guiding future target identification. Full article

Ferroptosis is a new mode of cell death, which is characterized by inducing the accumulation of lipid peroxides dependent on iron ions and reactive oxygen species. It has been found that ferroptosis can lead to follicle atresia by promoting granulosa cell death and increasing its reactive oxygen species content, but the specific mechanism has not been elucidated. Through transcriptome sequencing, we found that ferroptosis markers and related genes were upregulated in porcine atretic follicles. PTGS2 was found to be differentially expressed between atretic and healthy follicles. By inhibiting NF-κB nuclear translocation, inhibition of the PTGS2 gene expression reduced the degree of ferroptosis in granulosa cells and rescued granulosa cell death and oxidative stress caused by ferroptosis. Therefore, we propose that the NF-κB/PTGS2 axis plays a key role in ferroptosis-induced granulosa cell death, leading to follicular atresia. Melatonin, a neurohormone secreted by the pineal gland of the upper thalamus, is involved in the regulation of various metabolic, immune, reproductive, and other processes. In the ferroptosis treatment group, melatonin treatment alleviated the degree of ferroptosis (downregulation of ferroptosis marker genes and markers) and decreased the expression of PTGS2. In summary, we have demonstrated that melatonin inhibits ferroptosis via the NF-κB/PTGS2 axis in granulosa cells. Full article

It is widely accepted that chronic inflammation constitutes a significant mechanism that promotes the biological aging process. The pineal gland is regarded as being closely related to the control of the “life clock”. The present study aimed to determine the inflammation associated with pinealectomy in the rat hippocampus and to investigate the extent to which age stage impacts the severity of this inflammation. We evaluated the expression of the Akt/NF-kB signaling pathway in neurons and gliosis level in the dorsal hippocampus (dHipp) of rats subjected to sham surgery or pinealectomy at 3, 14, or 18 months of age. The assessment was conducted using immunohistochemistry. Removal of the pineal gland resulted in significant, region-specific increases in NF-kB expression in neurons of the dHipp in the youngest and middle-aged groups. However, the change in expression of the phosphorylated form of Akt (pAkt1) in neurons went in the opposite direction in these two age groups, and there were also regional differences. Pinealectomy triggered microgliosis in both young and old rats, but middle-aged rats were resistant to microglia activation. Conversely, astrogliosis was observed in young adult and middle-aged groups with melatonin deficiency in certain regions of the dHipp. It is noteworthy that young adult rats demonstrated the highest degree of vulnerability to inflammation associated with the loss of melatonin as a hormone. In contrast, middle-aged rats with pinealectomy exhibited a complex and partial adaptive response. These findings emphasize the dynamic and age-dependent nature of neuroinflammation following pinealectomy, underscoring the developmental stage as a critical determinant of inflammatory susceptibility. Full article

Circadian rhythms are endogenous biological cycles that regulate essential cardiovascular functions, including blood pressure, heart rate, vascular tone, and metabolic homeostasis. Disruption of these rhythms due to factors such as shift work, artificial light at night, irregular sleep–wake cycles, or mistimed eating has been increasingly recognized as an independent risk factor for cardiovascular disease. A growing body of evidence links circadian misalignment to key pathophysiological mechanisms, including endothelial dysfunction, oxidative stress, inflammation, and autonomic imbalance. Melatonin, a hormone produced primarily by the pineal gland, plays a central role in circadian regulation and exhibits potent antioxidant, anti-inflammatory, and cardiometabolic properties. This narrative review synthesizes current findings on the interplay between circadian disruption and cardiovascular risk, with a particular emphasis on the mechanistic and therapeutic role of melatonin. We also highlight the potential of chronotherapeutic strategies, such as timed melatonin supplementation, antihypertensive dosing, and time-restricted eating, to restore circadian alignment and improve cardiovascular outcomes. Despite promising data, translation into clinical practice remains limited. Future research should focus on identifying practical circadian biomarkers, refining chronotherapy protocols, and integrating circadian variables into risk models and clinical workflows. Full article

Light is a major environmental factor that regulates circadian rhythms and pineal melatonin synthesis. While the influence of nighttime light exposure on melatonin suppression has been extensively investigated, much less is known about the impact of photophase light wavelength on pineal function. The aim of the study was to determine the influence of monochromatic light during the photophase on diurnal changes in melatonin-related indoles in the rat pineal gland. Wistar rats were exposed for 7 days to 150 lx of monochromatic blue (463 ± 10 nm), green (523 ± 10 nm), or red (623 ± 10 nm) LED light, or to white fluorescent light (control), under a 12:12 light–dark cycle. Pineal glands were collected every 3 h over 24 h, and the indole content was analyzed by high-performance liquid chromatography. The results demonstrated that both the timing and course of N-acetylserotonin (NAS) and melatonin (MLT) rhythms were significantly affected by light wavelength. Blue light most effectively preserved the normal rhythmicity observed under full-spectrum white light, whereas green—and particularly red light—delayed nocturnal NAS and MLT synthesis. These changes were accompanied by concurrent alternations in rhythms of serotonin, its precursors, and metabolites. The data strongly suggest that spectral light composition during the photophase influences pineal indole metabolism via melanopsin-mediated phototransduction and possibly other retinal mechanisms. These findings may have implications for the design of artificial lighting environments in human life and animal housing. Full article

Plastic overconsumption has emerged as a major environmental pollutant, with degraded micro- and nanoplastic (MNP) particles being consumed by a vast variety of species. MNPs, particles < 5 mm, contain endocrine-disrupting chemicals (EDCs), which can bind to hormone receptors and disrupt the proper endocrinological function of a variety of organs. This review explores the toxicological impact of MNPs on the hypothalamus, pituitary gland, thyroid, pineal body, ovaries, and testes, as well as the effects of the endocrinological regulatory axes, including the hypothalamic–pituitary–gonadal (HPG), hypothalamic–pituitary–thyroid (HPT), and hypothalamic–pituitary–adrenal (HPA) axes. The disruption of these hormonal feedback systems leads to reproductive dysfunction, neurotoxicity, cytotoxicity, immunotoxicity, and metabolic disorders. The gonads are particularly susceptible, with studies demonstrating oxidative stress, cellular apoptosis, and infertility due to MNP exposure. Given the widespread presence of MNPs and their impact on human health, further research is critical to understand their long-term effects and develop strategies to reduce exposure. Full article

Chitosan is increasingly utilized in combination with melatonin in novel formulations for a wide range of therapeutic applications. As a biocompatible and biodegradable polymer, chitosan exhibits notable properties, including antioxidant, antimicrobial, moisturizing, and absorption capabilities, in addition to a high potential for chemical modification due to its functional groups. These characteristics make it a valuable material in biomedical, pharmaceutical, cosmetic, food packaging, and environmental applications. Melatonin, an indoleamine primarily synthesized in the pineal gland but also found in various peripheral organs and in diverse organisms—including plants, bacteria, and fungi—has been extensively investigated for its antioxidant, anti-apoptotic, and anti-inflammatory activities, as well as its roles in immunomodulation, mitochondrial function, and melanin biosynthesis. This review summarizes recent advances in the combined use of chitosan and melatonin, with emphasis on their synergistic effects in wound healing, anti-cancer therapies, tissue engineering (i.e., skin and bone regeneration), and drug delivery systems. Additional potential applications are discussed in the context of cosmetology, aesthetic medicine, and veterinary practice. Full article

Sleep deprivation (SD) induces significant neurobiological changes, including oxidative stress, neuroinflammation, and behavioural impairments. This study was designed as a proof of concept to assess the potential for modulating the effects of SD through a short-term seven-day administration of Cornus mas (C. mas) in a rapid eye movement (REM) SD rodent paradigm. Adult male Wistar rats were randomised in four groups (n = 7): control, C. mas (CM), sleep deprivation (SD), and sleep deprivation with C. mas (SD + CM). Behaviourally, SD induced hyperactivity and hyperlocomotion. SD determined histological alterations in the prefrontal cortex and corpus callosum myelin coupled with ultrastructural mitochondrial and cellular abnormalities in the prefrontal cortex, hippocampus, and pineal gland. Despite evidence of systemic oxidative stress coupled with decreased serum GABA and BDNF following SD, no significant changes were observed in redox markers or inflammatory cytokine levels (TNF-α, IL-1β) within the prefrontal cortex or hippocampus. C. mas extract has shown an overall modest modulatory action, mainly evidenced on behavioural, histological, and ultrastructural parameters. Taken together, these findings highlight behavioural changes and region-specific molecular and structural abnormalities following prolonged REM SD in rats. Full article

The Latin (De Homine, 1662, 1664) and French (L’Homme, 1664) editions of René Descartes’ Treatise on Man present different iconographic traditions, but the iconography of the Latin editions is little known. Dutch physician and botanist Florentius Schuyl edited De Homine and illustrated it himself with a mix of woodcut and copperplate illustrations. This paper examines Schuyl’s innovative depictions of purported dynamic aspects of the pineal gland as claimed by Descartes: (1) repeatedly illustrating the pineal gland as the corporeal–spiritual linkage of the brain and soul; and (2) using a movable flap anatomy to illustrate the pineal gland as a motile structure that both responds to and directs animal spirits. None of the canonical illustrations in the later French edition attempted to depict the corporeal–spiritual linkage of the brain and soul, and the modest attempts in the French edition to depict the motility of the pineal gland relied simply on superimposition of two purported positions of the gland, a technique also employed by Schuyl. This paper also reviews how Schuyl’s illustration of a corporeal–spiritual linkage of the brain and soul in a goat sharply contrasts with his written defense of Descartes’ bête-machine doctrine in the extended preface to De Homine. Full article