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Objective Methods Results Conclusions Pineal gland volume (PGV), which is associated with sleep and circadian rhythm, is known to be changed in some psychiatric disorders such as major depression, mood disorders and schizophrenia. This study aimed to compare the PGV of children with mild and moderate intellectual disability (ID) and healthy children.This multicentre retrospective study included 40 children with ID (patient group), aged 6–12 years and 40 age‐ and sex‐matched healthy children (control group). The children were examined for their sociodemographic characteristics and for PGV using magnetic resonance imaging.The PGV of the patient group was significantly larger than that of the controls (p = 0.023). There was no statistically significant difference in PGV between mild and moderate ID. A moderate and positive correlation was found between Weschler Intelligence Scale for Children‐revised (WISC‐R) performance score and PGV (p = 0.049, r = 0.313) only in the patient group. In the receiver operating characteristic analysis, the area under the curve was 0.648, and the sensitivity was 70.0%, and the specificity was 60.0%.In conclusion, this study demonstrated that the increased PGV levels were associated with autism spectrum disorder (ASD) and PGV could be a risk factor in the aetiology of ID. Further research with larger sample sizes is needed to clarify this issue. [ABSTRACT FROM AUTHOR]

Melatonin is produced in the pineal gland under very tight control through the influences of light and the suprachiasmatic nucleus. As such, melatonin circulates in the blood at levels <3 pg/ml during the day and is only actively secreted at night reaching levels of approximately 100 pg/ml. As a consequence of binding to plasma proteins, free melatonin appears in saliva at approximately one third the plasma concentration. Measurement of melatonin is technically challenging because of these very low concentrations and while a number of commercial immunoassay kits are available and mass spectrometry assay methods have been published, not all are fit for purpose and can lead to unreliable conclusions. In this review I discuss the aspects of pineal melatonin production that saliva melatonin reflects, the factors influencing melatonin production or metabolism, saliva collection and analysis methods. Examples are provided of the appropriate use of saliva melatonin measurements; Dim Light Melatonin Onset (DLMO) assessment, impact of light on melatonin and the monitoring of rhythms prior to specific treatments. Examples of inappropriate use of saliva melatonin measurements are also provided including the use of poorly validated assays, morning saliva collections, attempts to stimulate melatonin, and linking specific illnesses to saliva melatonin levels. [ABSTRACT FROM AUTHOR]

Our study concentrated on the expression of miRNA-375 in the hypothalamic-pituitary-gonadal axis of female Hu sheep. The investigation involved cloning the precursor sequence of miR-NA-375, followed by comparison with database entries and subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In our approach, we obtained ovaries, thalamus, cerebellum, brain, uterus, pituitary gland, hypothalamus, and pineal gland from fertile but nonpregnant Hu ewes. MiRNA extraction kit was used to extract miRNA from the above eight tissues. Real-time fluorescent quantitative polymerase chain reaction was used to evaluate the role of miR-375 in the hy-pothalamic-pituitary-gonadal axis. The results of miR-375 precursor sequence cloning were compared with those of Anopheles gambiae, Apis mellifera, Bos taurus, Drosophila melanogaster, Danio rerio, Fugu rubripes, Gallus gallus, Homo sapiens, Monodelphis domestica, Macaca mulatta, Mus musculus, Pan troglodytes, Rattus norvegicus, Tetraodon nigroviridis, Xenopus tropicalis miR-375 in miRBase database. It was found that oar-miR-375 was highly conserved. Notably, miR-375 expression in the pineal gland was significantly higher (p < 0.01) than that in the ovaries, thalamus, cerebellum, brain, uterus, pituitary gland, hypothalamus. The study also involved predicting miR-375 target genes. GO and KEGG enrichment analyses of these predicted target genes revealed that miR-375 is involved in 182 biological processes, affects 186 cellular components, and participates in 184 molecular functions. In terms of pathway enrichment, miR-375 was linked to nine pathways, including the Hippo, Wnt, and mTOR signaling pathways. This study has validated the interaction between miR-375 and its target gene FZD4, which can be recognized and bound to produce effects. These findings lead to the inference that miR-375 may play a crucial regulatory role in sheep reproduction through the Hippo pathway and Wnt pathway, laying a foundation for further exploration of miR-375's role in this domain. [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is a complex syndrome of neurological deficits due to stenosis or occlusion of the carotid and vertebral arteries for which there is still no effective treatment. Melatonin, a hormone secreted by the pineal gland, has multiple biological effects, such as antioxidant and anti-inflammatory properties, circadian rhythm regulation, and tissue regeneration, demonstrating potential applications in the treatment of IS. The aim of this study was to investigate key melatonin-regulated genes associated with IS using transcriptome sequencing and bioinformatics analyses and to explore their potential mechanisms of action in the disease process. We obtained gene expression data related to ischemic stroke (IS) from the Gene Expression Omnibus (GEO) database and identified candidate genes using machine learning algorithms. We then assessed the predictive power of these genes using PPI network analysis and diagnostic models. Finally, a series of enrichment analyses identified four key genes: ADM, PTGS2, MMP9, and VCAN. In addition, we determined the mRNA levels of these four key genes in an IS rat model using qPCR and found that all of these genes were significantly upregulated in the IS model compared to the control group, which is consistent with the results of previous analyses. Meanwhile, these genes have biological functions such as regulating vascular tone, participating in the inflammatory response, influencing tissue remodeling, and regulating cell adhesion and proliferation, playing key roles in the pathogenesis of IS. Therefore, we suggest that these four key genes may serve as prospective biomarkers for IS and help predict the risk of developing IS. In conclusion, this study elucidates for the first time the potential role of melatonin in the pathogenesis of IS and lays the foundation for in-depth studies on the functions of these key genes in the pathophysiology of IS and their potential applications in clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Most vertebrates have a rhodopsin gene with a five-exon structure for visual photoreception. By contrast, teleost fishes have an intron-less rhodopsin gene for visual photoreception and an intron-containing rhodopsin (exo-rhodopsin) gene for pineal photoreception. Here, our analysis of non-teleost and teleost fishes in various lineages of the Actinopterygii reveals that retroduplication after branching of the Polypteriformes produced the intron-less rhodopsin gene for visual photoreception, which converted the parental intron-containing rhodopsin gene into a pineal opsin in the common ancestor of the Teleostei. Additional analysis of a pineal opsin, pinopsin, shows that the pinopsin gene functions as a green-sensitive opsin together with the intron-containing rhodopsin gene for pineal photoreception in tarpon as an evolutionary intermediate state but is missing in other teleost fishes, probably because of the redundancy with the intron-containing rhodopsin gene. We propose an evolutionary scenario where unique retroduplication caused a "domino effect" on the functional diversification of teleost visual and pineal opsin genes. [ABSTRACT FROM AUTHOR]

Melatonin is synthesized in and secreted from the pineal glands and regulates circadian rhythms. Although melatonin has been reported to modulate the activity of ion channels in several tissues, its effects on pineal ion channels remain unclear. In the present study, the effects of melatonin on voltage-gated K+ (KV) channels, which play a role in regulating the resting membrane potential, were examined in rat pinealocytes. The application of melatonin reduced pineal KV currents in a concentration-dependent manner (IC50 = 309 µM). An expression analysis revealed that KV4.2 channels were highly expressed in rat pineal glands. Melatonin-sensitive currents were abolished by the small interfering RNA knockdown of KV4.2 channels in rat pinealocytes. In human embryonic kidney 293 (HEK293) cells expressing KV4.2 channels, melatonin decreased outward currents (IC50 = 479 µM). Inhibitory effects were mediated by a shift in the voltage dependence of steady-state inactivation in a hyperpolarizing direction. This inhibition was observed even in the presence of 100 nM luzindole, an antagonist of melatonin receptors. Melatonin also blocked the activity of KV4.3, KV1.1, and KV1.5 channels in reconstituted HEK293 cells. The application of 1 mM melatonin caused membrane depolarization in rat pinealocytes. Furthermore, KV4.2 channel inhibition by 5 mM 4-aminopyridine attenuated melatonin secretion induced by 1 µM noradrenaline in rat pineal glands. These results strongly suggest that melatonin directly inhibited KV4.2 channels and caused membrane depolarization in pinealocytes, resulting in a decrease in melatonin secretion through parasympathetic signaling pathway. This mechanism may function as a negative-feedback mechanism of melatonin secretion in pineal glands. [ABSTRACT FROM AUTHOR]

Migraine, a complex disorder, is characterized by recurrent headache episodes. The production of melatonin in the pineal gland, which is crucial for controlling circadian rhythms and sleep–wake cycles, is altered in various conditions, including neurological disorders such as migraine. Recent studies underscore the significance of serum melatonin levels in patients with chronic and episodic migraine, the focus of this study. This case‒control study, conducted from September 2017 to June 2020 in Tehran, Iran, selected potential participants aged 18–65 years from a headache clinic at Sina Hospital (affiliated with Tehran University of Medical Sciences). Both episodic migraine and chronic migraine were diagnosed following the diagnostic criteria in the International Classification of Headache Disorders' third edition. Melatonin levels were measured according to the instructions of the ELISA kits. There were significant differences in the frequency of headache days and the duration of abortive medication usage between the two groups (P value < 0.001). Besides, analysis revealed significantly lower serum melatonin levels in patients with episodic ((80.45–45.06) 72.83) and chronic migraine ((154.34–63.34) 70.38, P value < 0.001) than in healthy controls (281.25–160.86) 280). Although no considerable differences were found between episodic and chronic migraine patients, the current study demonstrated that serum melatonin levels were substantially greater in healthy controls than in patients with migraine. [ABSTRACT FROM AUTHOR]

Chronic pain due to peripheral neuropathy can lead to sleep disorders that significantly worsen the patient's quality of life. Previously, we conducted brain wave measurements in a rat model of neuropathic pain and identified its potential as a model for sleep disorders associated with chronic pain (reported). In this study, we quantified melatonin secretion and assessed its circadian rhythm in a rat model of pain-induced sleep disorder. To create a model of chronic constriction injury (CCI), rats were loosely tied around the sciatic nerve, with approximately 1 mm spacing, 14 days before the experiment. Rats with no ties around the sciatic nerve were used as controls. Electroencephalograms and electromyograms were recorded for 3 days, and the episodes of waking, REM sleep, and non-REM sleep were compared between the groups. The samples for microanalysis were collected every 30 min and used for melatonin analysis. Compared to the control group, the CCI model group exhibited an increase in wake episodes and a decrease in non-REM sleep episodes. Analysis of the area under the curve of melatonin secretion revealed a significant increase in melatonin secretion and a loss of circadian rhythm in the CCI model group. Melatonin secretion markedly increased accompanied by loss of circadian rhythm in a rat model of CCI. Further studies investigating the causal relationship between neuropathic pain and melatonin secretion are warranted. [ABSTRACT FROM AUTHOR]

Purpose: Pineal gland (PG) is a structure located in the midline of the brain, and is considered as a main part of the epithalamus. There are reports on the role of this area for brain function by hormone secretion, as well as few reports on its role in brain cognition. However, little knowledge is available on the PG, and in particular on the structural connectivity of this region with the other brain structures. Methods: Using diffusion-weighted images collected by a 3T MRI scanner, and using a sample of 61 (29 F) mentally and physically healthy young individuals in the age range of 20–30 years old, we tried to extract the white matter bundles connected to the PG. Based on prior knowledge, seven target bundles were suggested to be between the PG body and the PG roots, Pons, Periventricular region, thalamus, caudate, lentiform, suprachiasmatic nuclei, and the supercervical ganglia. Results: Nearly all the target bundles were successfully extracted, with the exception of the lentiform. Rate of identification of the tracts was different, with the bundle between the PG body and roots having the highest identification rate (97%); then it was with the Pons (70%), Periventricular region (57%), SCN (55%), left thalamus (52%), right thalamus (47%), left caudate (27%) and right caudate (22%). Conclusion: This study is an attempt to expand our knowledge on the neuroanatomy of the PG, which might help for identifying further roles for it in brain functionality, and also be a help for the treatment of some disorders in the future. [ABSTRACT FROM AUTHOR]

The ways in which animals sense the world changes throughout development. For example, young of many species have limited visual capabilities, but still make social decisions, likely based on information gathered through other sensory modalities. Poison frog tadpoles display complex social behaviors that have been suggested to rely on vision despite a century of research indicating tadpoles have poorly-developed visual systems relative to adults. Alternatively, other sensory modalities, such as the lateral line system, are functional at hatching in frogs and may guide social decisions while other sensory systems mature. Here, we examined development of the mechanosensory lateral line and visual systems in tadpoles of the mimic poison frog (Ranitomeya imitator) that use vibrational begging displays to stimulate egg feeding from their mothers. We found that tadpoles hatch with a fully developed lateral line system. While begging behavior increases with development, ablating the lateral line system inhibited begging in pre-metamorphic tadpoles, but not in metamorphic tadpoles. We also found that the increase in begging and decrease in reliance on the lateral line co-occurs with increased retinal neural activity and gene expression associated with eye development. Using the neural tracer neurobiotin, we found that axonal innervations from the eye to the brain proliferate during metamorphosis, with few retinotectal connections in recently-hatched tadpoles. We then tested visual function in a phototaxis assay and found tadpoles prefer darker environments. The strength of this preference increased with developmental stage, but eyes were not required for this behavior, possibly indicating a role for the pineal gland. Together, these data suggest that tadpoles rely on different sensory modalities for social interactions across development and that the development of sensory systems in socially complex poison frog tadpoles is similar to that of other frog species. [Display omitted] • Ranitomeya imitator tadpoles hatch with fully developed lateral line systems. • Use of mechanosensory stimuli for begging is dependent on developmental stage. • The visual system of R. imitator tadpoles continues to develop through metamorphosis. • When visual capabilities are poor, tadpoles rely more on mechanosensory inputs. [ABSTRACT FROM AUTHOR]

Melatonin (MTN) is a neuro-hormone released from the pineal gland. MTN secretion is regulated by different neuronal circuits, including the retinohypothalamic tract and suprachiasmatic nucleus (SCN), which are affected by light. MTN is neuroprotective in various neurodegenerative diseases, including Parkinson's disease (PD). MTN circulating level is highly blunted in PD. However, the underlying causes were not fully clarified. Thus, the present review aims to discuss the potential causes of blunted MTN levels in PD. Distortion of MTN circadian rhythmicity in PD patients causies extreme daytime sleepiness. The underlying mechanism for blunted MTN response may be due to reduction for light exposure, impairment of retinal light transmission, degeneration of circadian pacemaker and dysautonomia. In conclusion, degeneration of SCN and associated neurodegeneration together with neuroinflammation and activation of NF-κB and NLRP3 inflammasome, induce dysregulation of MTN secretion. Therefore, low serum MTN level reflects PD severity and could be potential biomarkers. Preclinical and clinical studies are suggested to clarify the underlying causes of low MTN in PD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Tranexamic acid (TXA) is widely used among young women because of its ability to whiten skin and treat menorrhagia. Nevertheless, its potential effects on oocyte maturation and quality have not yet been clearly clarified. Melatonin (MT) is an endogenous hormone released by the pineal gland and believed to protect cells from oxidative stress injury. In the present study, we used an in vitro maturation model to investigate the toxicity of TXA and the protective role of MT in mouse oocytes. Compared with the control group, the TXA-exposed group had significantly lower nuclear maturation (57.72% vs. 94.08%, P < 0.001) and early embryo cleavage rates (38.18% vs. 87.66%, P < 0.001). Further study showed that spindle organization (52.56% vs. 18.77%, P < 0.01) and chromosome alignment (33.23% vs. 16.66%, P < 0.01) were also disrupted after TXA treatment. Mechanistically, we have demonstrated that TXA induced early apoptosis of oocytes (P < 0.001) by raising the level of reactive oxygen species (P < 0.001), which was consistent with an increase in mitochondrial damage (P < 0.01). Fortunately, all these effects except the spindle defect were successfully rescued by an appropriate level of MT. Collectively, our findings indicate that MT could partially reverse TXA-induced oocyte quality deterioration in mice by effectively improving mitochondrial function and reducing oxidative stress-mediated apoptosis. NEW & NOTEWORTHY: Tranexamic acid is increasingly used to whiten skin, reverse dermal damages, and treat heavy menstrual bleeding in young women. However, its potential toxicity in mammalian oocytes is still unclear. Our study revealed that tranexamic acid exposure impaired the mouse oocyte quality and subsequent embryo development. Meanwhile, melatonin has been found to exert beneficial effects in reducing tranexamic acid-induced mitochondrial dysfunction and oxidative stress. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is characterized as a microvascular disease. Nonproliferative diabetic retinopathy (NPDR) presents with alterations in retinal blood flow and vascular permeability, thickening of the basement membrane, loss of pericytes, and formation of acellular capillaries. Endothelial–mesenchymal transition (EndMT) of retinal microvessels may play a critical role in advancing NPDR. Melatonin, a hormone primarily secreted by the pineal gland, is a promising therapeutic for DR. This study explored the EndMT in retinal microvessels of NPDR and its related mechanisms. The effect of melatonin on the retina of diabetic rats was evaluated by electroretinogram (ERG) and histopathologic slide staining. Furthermore, the effect of melatonin on human retinal microvascular endothelial cells (HRMECs) was detected by EdU incorporation assay, scratch assay, transwell assay, and tube formation test. Techniques such as RNA‐sequencing, overexpression or knockdown of target genes, extraction of cytoplasmic and nuclear protein, co‐immunoprecipitation (co‐IP), and multiplex immunofluorescence facilitated the exploration of the mechanisms involved. Our findings reveal, for the first time, that melatonin attenuates diabetic retinopathy by regulating EndMT of retinal vascular endothelial cells via inhibiting the HDAC7/FOXO1/ZEB1 axis. Collectively, these results suggest that melatonin holds potential as a therapeutic strategy to reduce retinal vascular damage and protect vision in NPDR. [ABSTRACT FROM AUTHOR]

Embryonal and pineal tumours represent a diverse group of central nervous system (CNS) neoplasms. While many of the small round blue cell tumours that make up the embryonal neoplasms share similar histologic qualities, there are several morphologic and cytologic characteristics that are useful in distinguishing different tumour types. Similarly, pineal parenchymal tumours represent clinically diverse tumours, ranging from benign to overtly malignant. The most recent iteration of the World Health Organization Classification of CNS Tumours expanded greatly on the significance of molecular alterations in brain tumour diagnostics. In this article, we summarize the salient cytologic and histologic features of CNS embryonal and pineal tumours, and highlight diagnostically relevant molecular alterations within each tumour type. In the article by Reznicek et al., the authors provide a comprehensive overview of the cytologic, histologic, and molecular features of embryonal tumours and pineal gland tumours of the central nervous system. Integrating high‐quality photomicrographs with the most up‐to‐date knowledge of molecular diagnostics, the article will serve as an invaluable resource for practicing pathologists. [ABSTRACT FROM AUTHOR]

Objectives: There is no enough stereological study that seriously mentions maternal olfactory disorders among the causes of pineal gland insults. This study sought to examine the connection between lesions caused by olfactory bulbectomy and changes in the pineal gland in ratsMethods: A total of 24 male rats were used in the experiment, 5 control, 6 SHAM and 13 study. After a 1 mm burrhole was opened in the midfrontal-interpupillary line for the subjects in the SHAM and study groups, only the olfactory dura was opened in the SHAM group, while the olfactory bulbs were crushed in study group. They were sacrificed after a two-month follow-up. The number of calcified pineal cells (n/mm3) determined. Results analyzed with the Mann-Witney U test.Results: The mean calcified pineal cells numbers (n/mm3) were measured as per cubic milimeters as: (7±2) x103/mm3) in control (Group I); (15±3) x103 in SHAM (Group II); (34±9) x103 in study group (Group III). P

Objective: To investigate whether melatonin (MT) secretion in different parts of the gastrointestinal tract (GIT) exhibits seasonal variations and its correlation with immune regulation. Methods: Sixty Sprague-Dawley rats were divided into control and model groups, and the pineal gland was removed in the model group. Stomach, jejunum, ileum, and colon tissues were obtained during the spring equinox, summer solstice, beginning of autumn, autumn equinox, and winter solstice. The levels of MT, MT receptors (MR), arylalkylamine N-acetyltransferase (AANAT), hydroxyindole-O-methyltransferase (HIOMT), interleukin-2 (IL-2), and interleukin-10 (IL-10) in the GIT were measured using enzyme-linked immunosorbent assay. Results: Except for the stomach, the jejunum, ileum, and the colon showed seasonal tendencies in MT secretion. In the control group, MT secretion in the jejunum and ileum was the highest in the long summer, and colonic MT secretion was the highest in winter. In the model group, MT levels in the colon were highest in the summer. The seasonal rhythms of the MR, AANAT, HIOMT, IL-2, and IL-10 in the colon were roughly similar to those of MT, and changed accordingly after pinealectomy. Conclusions: Gastrointestinal MT secretion is related to seasonal changes, and MT secretion in each intestinal segment is influenced by different seasons. The biological effects of MT in the gut are inextricably linked to the mediation of MR, and a hormone-receptor linkage exists between MT and MR. The effect of seasonal changes on the gastrointestinal immune system may be mediated through the regulation of seasonal secretion of MT.

Pineal gland tumors are significant despite being rare (

Melatonin, the hormone of the pineal gland, possesses a range of physiological functions, and recently, its anticancer effect has become more apparent. A more thorough understanding of molecular alterations in the components of several signaling pathways as new targets for cancer therapy is needed because of current innate restrictions such as drug toxicity, side effects, and acquired or de novo resistance. The PI3K/Akt/mTOR pathway is overactivated in many solid tumors, such as breast and ovarian cancers. This pathway in normal cells is essential for growth, proliferation, and survival. However, it is an undesirable characteristic in malignant cells. We have reviewed multiple studies about the effect of melatonin on breast and ovarian cancer, focusing on the PI3K/Akt/mTOR pathway. Melatonin exerts its inhibitory effects via several mechanisms. A: Downregulation of downstream or upstream components of the signaling pathway such as phosphatase and tensin homolog (PTEN), phosphatidylinositol (3,4,5)‐trisphosphate kinase (PI3K), p‐PI3K, Akt, p‐Akt, mammalian target of rapamycin (mTOR), and mTOR complex1 (mTORC1). B: Apoptosis induction by decreasing MDM2 expression, a downstream target of Akt, and mTOR, which leads to Bad activation in addition to Bcl‐XL and p53 inhibition. C: Induction of autophagy in cancer cells via activating ULK1 after mTOR inhibition, resulting in Beclin‐1 phosphorylation. Beclin‐1 with AMBRA1 and VPS34 promotes PI3K complex I activity and autophagy in cancer cells. The PI3K/Akt/mTOR pathway overlaps with other intracellular signaling pathways and components such as AMP‐activated protein kinase (AMPK), Wnt/β‐catenin, mitogen‐activated protein kinase (MAPK), and other similar pathways. Cancer therapy can benefit from understanding how these pathways interact and how melatonin affects these pathways. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumor (SFT) is a type of fibroblastic neoplasm that can occur in various parts of the body, with SFT of the pineal gland being exceedingly rare. We report the case of a 58-year-old male presenting with recurrent hiccups, acid reflux, and headache. Magnetic resonance imaging revealed an occupying lesion in the pineal region, suggestive of a neoplastic process. Intraoperatively, the lesion was located in the pineal region, exhibiting a grayish-red color, and was largely resected. Pathological examination confirmed the diagnosis of solitary fibrous tumor (CNS WHO Grade 1). Postoperatively, the patient was supplemented with radiotherapy, and long-term follow-up showed no signs of recurrence or metastasis. [ABSTRACT FROM AUTHOR]

Introduction: The reproductive system is tightly regulated by environmental and physiological signals. Melatonin, known as the hormone of darkness, plays a crucial role in regulating both the circadian and reproductive systems in mammals. Hypothyroidism is a key endocrine disorder that harms the reproductive system. Despite many studies on melatonin's effects on the reproductive system, there is conflicting information regarding melatonin synthesis modulation in hypothyroidism. The objective of this study was to investigate the modulation of plasma melatonin levels and gene expression of Aanat and Asmt in the pineal gland and gonads of rats with hypothyroidism at different times of the day. Methods: Female and male Wistar rats were divided into control and hypothyroid groups. Hypothyroidism was induced using propylthiouracil (PTU) for 15 days, rats were euthanized six hours after lights on (ZT6), before lights off (ZT11.5), and six hours after lights off (ZT18). Free thyroxine (FT4) and melatonin were quantified in plasma, and gene expressions of melatonin synthesizing enzymes (Aanat and Asmt) were measured in pineal and sexual organs (testis and ovary). Also, morphological analysis was performed in sexual organs. Results: The results reveal some disparities between the sexes. Hypothyroidism reduced antral and primary follicles in the ovary, and reduced the weight of testis, epididymis, and prostate. In relation to gene expression, we observed a reduction in Aanat expression in the pineal gland during the light phase (ZT6), and in males, this reduction occurred during the dark phase (ZT18). Regarding Asmt expression, there was a decrease in females also during the dark phase (ZT18). In the gonads, there was an increase in expression in both sexes at ZT11.5. Additionally, it was interesting to observe the association between FT4 levels and Asmt expression in the gonads. Conclusions: This study showed that acute hypothyroidism can affect components of the melatonergic system in gonads, particularly gene expression of melatonin synthesis enzymes (Aanat and Asmt) contributing to changes in reproduction organs during disease progression. These findings enhance our understanding of melatonin synthesis in the reproductive system during hypothyroidism, showing distinct responses in male and female rats, and suggest that hypothyroidism affects the circadian rhythmicity of melatonin synthesis in a sex-dependent manner. [ABSTRACT FROM AUTHOR]

Intracranial physiological calcifications are usually seen in Post-mortem Computed Tomography (PMCT) and are difficult to note with naked-eye examination during conventional autopsy. Studies on intracerebral calcifications in PMCT are few. Moreover, such studies may be of interest from the clinical perspective in order to compare physiological and pathological intracranial calcifications. Hence, the authors aimed to calculate the incidence of calcification of the pineal gland and choroid plexus in the lateral ventricle in brain PMCT and its association with age, sex, type of death, and manner of death. The authors studied 620 PMCT head scans of the deceased whose ages ranged from 2 months to 97 years (mean ± SD is 38.83 ± 15.91). A total of 59.68% had pineal calcification, and 47.42% had choroid plexus calcification with a male preponderance. A statistically significant association was present between the studied calcifications and age, sex, type of death, and manner of death. The calcification was higher in the pineal gland than in the choroid plexus until the fifth decade, and post fifth decade the choroid plexus calcification was more common. The presence of calcification was higher among the suicidal deaths when compared with the non-suicidal deaths with a statistically significant association (p < 0.05). [ABSTRACT FROM AUTHOR]

Melatonin, a pineal gland hormone closely associated with the circadian rhythm, has been trending over the past years as an over-the-counter medication to aid with sleep disturbances. Although generally believed to be safe, recent studies show negative inotropic and chronotropic effects on the heart rate and blood pressure in humans. Several studies suggested that melatonin induces cardiac vagal tone and affects heart rate and mean arterial pressure. Limited literature is currently available on the effects of melatonin beyond its sleep function. We present a case of a healthy 22-year-old male who visited the emergency department reporting palpitations and dizziness following the ingestion of 20 mg of melatonin. Subsequent examinations revealed marked bradycardia. Fortunately, the patient experienced spontaneous resolution of the bradycardia without necessitating intervention after a few hours of observation, and he was observed and discharged. [ABSTRACT FROM AUTHOR]

Melatonin, an endogenous indolamine derived from tryptophan, is primarily synthesized by the pineal gland in mammals and regulated by a complex neural system. Its release follows a circadian rhythm, which is crucial for regulating physiological processes in response to light–dark cycles in both humans and animals. In this review, we report that the presence of this hormone in bovine milk, with significant differences in concentration between daytime and nighttime milking, has increased interest in milk as a natural source of bioactive molecules. Melatonin lowers cortisol levels at night, reduces body temperature and blood pressure, coinciding with decreased alertness and performance, acts as an antioxidant and anti-inflammatory agent, modulates the immune system, offers neuroprotective benefits, and supports gastrointestinal health by scavenging free radicals and reducing oxidative stress in dairy cows. Many factors influence the release of melatonin, such as the intensity of artificial lighting during nighttime milking, the frequency of milkings, milk yield, and genetic differences between animals. Nocturnal milking under low-intensity light boosts melatonin, potentially reducing oxidative damage and mastitis risk. Additionally, ultra-high temperature (UHT) treatment does not significantly affect the melatonin content in milk. However, further research on its stability during milk processing and storage is crucial for ensuring product efficacy. In some countries, nighttime milk with naturally elevated melatonin content is already commercialized as a natural aid for sleep. Thus, naturally melatonin-rich milk may be a promising alternative to synthetic supplements for promoting better sleep and overall well-being. [ABSTRACT FROM AUTHOR]

In mammals, seasonal opportunities and challenges are anticipated through programmed changes in physiology and behavior. Appropriate anticipatory timing depends on synchronization to the external solar year, achieved through the use of day length (photoperiod) as a synchronizing signal. In mammals, nocturnal production of melatonin by the pineal gland is the key hormonal mediator of photoperiodic change, exerting its effects via the hypothalamopituitary axis. In this review/perspective, we consider the key developments during the history of research into the seasonal synchronizer effect of melatonin, highlighting the role that the pars tuberalis–tanycyte module plays in this process. We go on to consider downstream pathways, which include discrete hypothalamic neuronal populations. Neurons that express the neuropeptides kisspeptin and (Arg)(Phe)–related peptide‐3 (RFRP‐3) govern seasonal reproductive function while neurons that express somatostatin may be involved in seasonal metabolic adaptations. Finally, we identify several outstanding questions, which need to be addressed to provide a much thorough understanding of the deep impact of melatonin upon seasonal synchronization. [ABSTRACT FROM AUTHOR]

Colistin is renowned as a last‐resort antibiotic due to the emergence of multidrug‐resistant pathogens. However, its potential toxicity significantly hampers its clinical utilization. Melatonin, chemically known as N‐acetyl‐5‐hydroxytryptamine, is an endogenous hormone produced by the pineal gland and possesses diverse biological functions. However, the protective role of melatonin in alleviating antibiotic‐induced intestinal inflammation remains unknown. Herein, we reveal that colistin stimulation markedly elevates intestinal inflammatory levels and compromises the gut barrier. In contrast, pretreatment with melatonin safeguards mice against intestinal inflammation and mucosal damage. Microbial diversity analysis indicates that melatonin supplementation prevents a reduction in the abundance of Erysipelotrichales and Bifidobacteriales, as well as an increase in Desulfovibrionales abundance, following colistin exposure. Remarkably, short‐chain fatty acids (SCFAs) analysis shows that propanoic acid contributes to the protective effect of melatonin on colistin‐induced intestinal inflammation. Furthermore, the protection effects of melatonin and propanoic acid on LPS‐induced cellular inflammation in RAW 264.7 cells are confirmed. Mechanistic investigations suggest that intervention with melatonin and propanoic acid can repress the activation of the TLR4 signal and its downstream NF‐κB and MAPK signaling pathways, thereby mitigating the toxic effects of colistin. Our work highlights the unappreciated role of melatonin in preventing the potential detrimental effects of colistin on intestinal health and suggests a combined therapeutic strategy to effectively manage intestinal infectious diseases. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionIn recent years, it has been known that the melatonin hormone, secreted from the pineal gland, possesses significant antioxidant activity. This study explores the therapeutic effect of melatonin on the deleterious effects of deltamethrin, a pyrethroid pesticide extensively used worldwide, including in Türkiye, on mouse liver cells.Hepatocytes from Balb/C mice were isolated using a two-stage perfusion method, resulting in over 85% live hepatocytes. The isolated cells were cultured with different doses of deltamethrin (1 and 10 µM) and melatonin (100 µM) for 24 and 48 hours. At the conclusion of the culture period, hepatocytes were extracted at the 24th and 48th hours, and Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), Total Oxidation Status (TOS), and DNA damages (8-hydroxy-2’-deoxyguanosine (8-OHdG)) were examined.While an increase in MDA, TOS, and DNA damage was observed in the deltamethrin-administered groups of hepatocytes, a decrease in TAC level was noted. It was determined that the applied deltamethrin had no effect on cell viability throughout the application period.Furthermore, it was observed that melatonin, when administered concurrently with deltamethrin, reduced the toxic effect of deltamethrin. This study suggests that melatonin has a protective effect against deltamethrin-induced damage in mouse hepatocyte cells. [ABSTRACT FROM AUTHOR]

The Institute of Physiology of the Czech Academy of Sciences (CAS) has been involved in the field of chronobiology, i.e., in research on temporal regulation of physiological processes, since 1970. The review describes the first 35 years of the research mostly on the effect of light and daylength, i.e., photoperiod, on entrainment or resetting of the pineal rhythm in melatonin production and of intrinsic rhythms in the central biological clock. This clock controls pineal and other circadian rhythms and is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. During the early chronobiological research, many original findings have been reported, e.g. on mechanisms of resetting of the pineal rhythm in melatonin production by short light pulses or by long exposures of animals to light at night, on modulation of the nocturnal melatonin production by the photoperiod or on the presence of high affinity melatonin binding sites in the SCN. The first evidence was given that the photoperiod modulates functional properties of the SCN and hence the SCN not only controls the daily programme of the organism but it may serve also as a calendar measuring the time of a year. During all the years, the chronobiological community has started to talk about “the Czech school of chronobiology”. At present, the today´s Laboratory of Biological Rhythms of the Institute of Physiology CAS continues in the chronobiological research and the studies have been extended to the entire circadian timekeeping system in mammals with focus on its ontogenesis, entrainment mechanisms and circadian regulation of physiological functions. [ABSTRACT FROM AUTHOR]

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Melatonin, the 'hormone of darkness' is a neuronal hormone secreted by the pineal gland and other extra pineal sites. Responsible for the circadian rhythm and seasonal behaviour of vertebrates and mammals, melatonin is responsible for regulating various physiological conditions and the maintenance of sleep, body weight and the neuronal activities of the ocular sites. With its unique amphiphilic structure, melatonin can cross the cellular barriers and elucidate its activities in the subcellular components, including mitochondria. Melatonin is a potential scavenger of oxygen and nitrogen-reactive species and can directly obliterate the ROS and RNS by a receptor-independent mechanism. It can also regulate the pro- and anti-inflammatory cytokines in various pathological conditions and exhibit therapeutic activities against neurodegenerative, psychiatric disorders and cancer. Melatonin is also found to show its effects on major organs, particularly the brain, liver and heart, and also imparts a role in the modulation of the immune system. Thus, melatonin is a multifaceted candidate with immense therapeutic potential and is still considered an effective supplement on various therapies. This is primarily due to rectification of aberrant circadian rhythm by improvement of sleep quality associated with risk development of neurodegenerative, cognitive, cardiovascular and other metabolic disorders, thereby enhancing the quality of life. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) is commonplace in today's fast-paced society. SD is a severe public health problem globally since it may cause cognitive decline and even neurodegenerative disorders like Alzheimer's disease. Melatonin (MT) is a natural chemical secreted by the pineal gland with neuroprotective effects. The purpose of this study was to investigate the protective effect and mechanism of MT on chronic sleep deprivation-induced cognitive impairment. A 3-week modified multi-platform method was used to create the SD rat model. The Morris water maze test (MWM), Tissue staining (including Hematoxylin and Eosin (H & E) staining, Nissl staining, and immunofluorescence), Western blot, Enzymelinked immunosorbent assay (ELISA), and Quantitative real-time polymerase chain reaction (qPCR) were used to investigate the protective effect and mechanism of MT in ameliorating cognitive impairment in SD rats. The results showed that MT (50 and 100 mg/kg) significantly improved cognitive function in rats, as evidenced by a shortening of escape latency and increased time of crossing the platform and time spent in the quadrant. Additionally, MT therapy alleviated hippocampus neurodegeneration and neuronal loss while lowering levels of pathogenic factors (LPS) and inflammatory indicators (IL-1ß, IL-6, TNF-a, iNOS, and COX2). Furthermore, MT treatment reversed the high expression of Aß42 and Iba1 as well as the low expression of ZO-1 and occludin, and inhibited the SD-induced TLR4/MyD88/NF-κB signaling pathway. In summary, MT ameliorated spatial recognition and learning memory dysfunction in SD rats by reducing neuroinflammation and increasing neuroprotection while inhibiting the TLR4/MyD88/NF-κB signaling pathway. Our study supports the use of MT as an alternate treatment for SD with cognitive impairment. [ABSTRACT FROM AUTHOR]

• prenatal LPS and early-life LL affect the expression profiles of genes at P30. • impact of combined interventions is smaller than that of individual interventions. • combined interventions increase the amplitude of expression rhythms in some genes. Exposure to lipopolysaccharide (LPS) during prenatal development leads to various changes in neurobiological and behavioural patterns. Similarly, continuous exposure to constant light (LL) during the critical developmental period of the circadian system affects gene expression in various tissues in adulthood. Given the reciprocal nature of the interaction between the circadian and the immune systems, our study primarily investigated the individual effects of both interventions and, more importantly, their combined effect. We aimed to explore whether there might be a potential synergistic effect on circadian rhythms and their parameters, focussing on the expression of clock genes, immune-related genes, and specific genes in the hippocampus, pineal gland, spleen and adrenal gland of rats at postnatal day 30. Our results show a significant influence of prenatal LPS and postnatal LL on the expression profiles of all genes assessed. However, the combination of prenatal LPS and postnatal LL only revealed an enhanced negative effect in a minority of the comparisons. In most cases, it appeared to attenuate the changes induced by the individual interventions, restoring the measured parameters to values closer to those of the control group. In particular, genes such as Nr1d1 , Aanat and Tph1 showed increased amplitude in the pineal gland and spleen, while the kynurenine enzymes Kynu and KatII developed circadian rhythmicity in the adrenal glands only after the combined interventions. Our data suggest that a mild immunological challenge during prenatal development may play a critical role in triggering an adaptive response of the circadian clock later in life. [ABSTRACT FROM AUTHOR]

Plasmodium, a digenetic parasite, requires a host and a vector for its life cycle completion. Most Plasmodium species display circadian rhythmicity during their intraerythrocytic cycle within the host, aiding in immune evasion. This rhythmicity, however, diminishes in in vitro cultures, highlighting the importance of host-derived signals for synchronizing the parasite's asexual cycle. Studies indicate a species–specific internal clock in Plasmodium, dependent on these host signals. Melatonin, a hormone the pineal gland produces under circadian regulation, impacts various physiological functions and is extensively reviewed as the primary circadian marker affecting parasite rhythms. Research suggests that melatonin facilitates synchronization through the PLC-IP3 signaling pathway, activating phospholipase C, which triggers intracellular calcium release and gene expression modulation. This evidence strongly supports the role of melatonin as a key circadian marker for parasite synchronization, presenting new possibilities for targeting the melatonin pathway when developing novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Primary brain tumors are a heterogeneous group of neoplasms, originating from glial and other cell types in the central nervous system (CNS). Despite advancements in technology and medicine, the prognosis for malignant brain tumors remains poor. This situation requires novel therapeutic approaches. Melatonin, a hormone produced by the pineal gland, regulates sleep and circadian rhythms. It also possesses various biological functions, such as antioxidant properties, immune modulation, and tumor suppression. This review analyzes existing research on the effects of melatonin on brain tumors, focusing on its therapeutic potential and mechanisms of action, and highlights melatonin’s promise as a complementary therapy against adult and pediatric high-grade gliomas. [ABSTRACT FROM AUTHOR]

Pineal gland tumors are significant despite being rare (<1%) among all brain tumors. Germ cell tumors are the most common among the pineal gland tumors. Often affecting young adults, pineal gland germ cell tumors are hard to diagnose due to different symptoms and potential spread. But they rarely show leptomeningeal spread and extracranial metastases. Other differentials include primary tumors of the pineal region, Pineal gliomas, and metastases. The leptomeningeal spread of these tumors has not been studied so far. Conventional radiological imaging modalities are routinely used to diagnose and evaluate these tumors. We report a case here showing a pineal gland tumor with leptomeningeal spread detected by 18F-FDG PET/CT. Our case shows how pineal gland tumors can behave unusually and how 18F-FDG PET/CT can be crucial for accurately assessing the extent of the disease in the body to provide effective treatment. This case report illustrates the rare type of spread of pineal gland tumor and how 18F-FDG PET/CT helps detect this rare type of metastasis, thereby helping in prognostication and deciding further treatment of the patient. [ABSTRACT FROM AUTHOR]

An innovative pharmaceutical form for administering melatonin, based on starch orodispersible film (ODF), was designed and prepared. The composition of the ODF included starch as the polymer matrix, the active drug melatonin, and a plasticizer. Melatonin, a natural hormone produced by the pineal gland in the brain, can be absorbed by passive diffusion across the mucous membrane, resulting in improved bioavailability when compared to conventional oral administration. This study shows a simple and efficient method for preparing melatonin-loaded orodispersible films with a physically stable and commercially viable matrix, suitable for use in the pharmaceutical industry. The films were prepared by treating the starch with microwave irradiation, followed by plasticization with glycerol, melatonin loading and drying by solvent casting. Mechanical tests showed the films' robustness, with a modulus of approximately 97 MPa, indicating good handling properties. Moisture uptake analysis showed fast water absorption, reaching about 150% within 2 min, indicating its fast oral disintegration potential. Disintegration tests in artificial saliva and dissolution studies indicated the release of the drug in minutes, indicating the potential properties of the film for oral drug delivery. To the best of our knowledge, there is no melatonin ODF based on starch described in the literature. [ABSTRACT FROM AUTHOR]

Disruptions of the circadian rhythm have shown that it can lead to significant health risks. Factors such as rapid travel across different time zones, increased exposure to artificial light, and the consumption of substances like caffeine contribute to this disruption. Understanding these disruptions and its causes is crucial for improving our health and in finding solutions. [ABSTRACT FROM AUTHOR]

Pineal-region tumors are a histologically heterogeneous group of tumors and represent a rare occurrence, accounting for less than 1% of all adult intracranial tumors. Among these, primary pineal malignant melanomas (PPM) represent an even rarer entity, with only twenty-five cases being reported in the literature to date. We present the case of a 65-year-old patient who presented in our department for progressive headache, gait disturbance and memory impairment. Magnetic resonance imaging (MRI) of the brain revealed a solid mass in pineal region, measuring 2.2 × 1.2 × 2.0 cm and causing obstructive hydrocephalus. He underwent a third ventriculostomy, but we failed to obtain a sample for diagnostic purposes. The intraoperative surprise was the presence, at the level of the third ventricle, of multiple melanin deposits, which were not picked up by the MRI. Although the biopsy could not be performed and had to be obtained by stereotactic biopsy in a second intervention, the endoscopy findings allowed for the correct staging of the intracranial disease and appropriate treatment management. [ABSTRACT FROM AUTHOR]

The origin of biological rhythms goes back to the very beginning of life. They are observed in the animal and plant world at all levels of organization, from cells to ecosystems. As early as the 18th century, plant scientists were the first to explain the relationship between flowering cycles and environmental cycles, emphasizing the importance of daily light-dark cycles and the seasons. Our temporal structure is controlled by external and internal rhythmic signals. Light is the main synchronizer of the circadian system, as daily exposure to light entrains our clock over 24 hours, the endogenous period of the circadian system being close to, but not exactly, 24 hours. In 1960, a seminal scientific meeting, the Cold Spring Harbor Symposium on Biological Rhythms, brought together all the biological rhythms scientists of the time, a number of whom are considered the founders of modern chronobiology. All aspects of biological rhythms were addressed, from the properties of circadian rhythms to their practical and ecological aspects. Birth of chronobiology dates from this period, with the definition of its vocabulary and specificities in metabolism, photoperiodism, animal physiology, etc. At around the same time, and right up to the present day, research has focused on melatonin, the circadian neurohormone of the pineal gland, with data on its pattern, metabolism, control by light and clinical applications. However, light has a double face, as it has positive effects as a circadian clock entraining agent, but also deleterious effects, as it can lead to chronodisruption when exposed chronically at night, which can increase the risk of cancer and other diseases. Finally, research over the past few decades has unraveled the anatomical location of circadian clocks and their cellular and molecular mechanisms. This recent research has in turn allowed us to explain how circadian rhythms control physiology and health. [ABSTRACT FROM AUTHOR]

Melatonin (5-methoxy-acetyl tryptamine) is a sleep-inducing hormone, and the pineal gland produces it in response to the circadian clock of darkness. In the body, MT1 and MT2 receptors are mostly found, having an orthosteric pocket and ligand binding determinants. Melatonin acts by binding on melatonin receptors, intracellular proteins, and orphan nuclear receptors. It inhibits adenyl cyclase and activates phospholipase C, resulting in gene expression and an intracellular alteration environment. Melatonin signaling pathways are also associated with other intracellular signaling pathways, i. e., cAMP/PKA and MAPK/ERK pathways. Relative expression of different proteins depends on the coupling profile of G protein, accounting pharmacology of the melatonin receptor bias system, and mediates action in a Gi-dependent manner. It shows antioxidant, antitumor, antiproliferative, and neuroprotective activity. Different types of melatonin agonists have been synthesized for the treatment of sleeping disorders. Researchers have developed therapeutics that target melatonin signaling, which could benefit a wide range of medical conditions. This review focuses on melatonin receptors, pharmacology, and signaling cascades; it aims to provide basic mechanical aspects of the receptor's pharmacology, melatonin's functions in cancer and neurodegenerative diseases, and any treatments and drugs designed for these diseases. This will allow a basic comparison between the receptors in question, highlighting any parallels and differences that may exist and providing fundamental knowledge about these receptors to future researchers. [ABSTRACT FROM AUTHOR]

Purpose The biodistribution of gallium-68-dotatate (Ga-68-dotatate) and standardized uptake values (SUVs) using non-time-of-flight (TOF) positron emission tomography/computed tomography (PET/CT) cameras is well established. However, with the eventual retirement of older PET cameras and their replacement with newer, highly sensitive TOF PET/CT cameras, where SUV max measurements are reportedly higher, updated knowledge of normal SUV max range is needed and, to our knowledge, not previously reported. Our objectives are as follows: To establish normal Ga-68-dotatate TOF SUV max database for common structures and to aid the visual detection of abnormalities objectively. To compare SUV max values using the TOF and non-TOF algorithms. Methods Fifty consecutive patients referred routinely to our nuclear medicine service (20 men, 30 women; median age 55 years) with presumed neuroendocrine tumors underwent Ga-68-dotatate scans on a PET-CT camera having capability of reconstructing both TOF/non-TOF images. Region of interests (ROIs) were drawn around 24 normal structures as well as the primary lesion with abnormal radiotracer uptake and SUV max was measured. The same ROI was analyzed using both algorithms simultaneously and both TOF and non-TOF SUV max values were compared. Results Twelve hundred ROIs were evaluated. Non-TOF Ga-68-dotatate uptake in normal structures was in alignment with previously published studies. As compared to non-TOF, TOF images had better target to background ratios visually. TOF SUV max was higher for all structures except for lung and brain. TOF SUV max was more than double in adrenals/uncinate process of the pancreas; approximately 1.8 times in abnormal lesions, lymph nodes, pineal gland; and greater than 1.5 times in thyroid, breast, and pancreatic head. Conclusion Normal database of Ga-68-dotatate TOF SUV max is provided for common structures to aid visual detection of abnormalities objectively. Overall, TOF SUV max measures higher in identical ROIs, with abnormal lesions measuring approximately 1.8 times higher versus non-TOF technology. These findings need to be taken in consideration when comparing patient scans imaged on different PET/CT technologies. [ABSTRACT FROM AUTHOR]

Purpose: Pineal Gland (PG) is a midline brain structure and part of the epithalamus, a dorsal posterior segment of the diencephalon. Most findings on the role of this structure in brain function are relevant to melatonin secretion, and only a few reports are available on its involvement in brain cognition. Materials and Methods: Due to some suggestions on the role of the diencephalon areas, including the PG, in the human memory system, we used data from two previous MRI studies on 32 and 295 healthy individuals, in order to identify first, if the PG shows activations in fMRI and during a memory retrieval task as well as showing functional connectivity with other brain structures, and second, if there are any associations between the PG volume and the memory scores of the individuals. Results: Using a standard PG atlas, our results showed significant activations in PG during memory retrieval, with the strength of these activations increasing with the increment of the cognitive load of the task. Also, PG showed functional connectivity with other brain structures during fMRI, the pattern of which also changed with the cognitive load of the retrieval. Finally, the volume of the PG showed significant associations with the scores of the memory tests. Conclusion: Our knowledge of the PG still needs improvement, and we hope our findings here could be a help for that as well as a help to better understand the mechanisms of memory storage and retrieval in humans.

Purpose: Pineal Gland (PG) is a midline brain structure and part of the epithalamus, a dorsal posterior segment of the diencephalon. Most findings on the role of this structure in brain function are relevant to melatonin secretion, and only a few reports are available on its involvement in brain cognition. Materials and Methods: Due to some suggestions on the role of the diencephalon areas, including the PG, in the human memory system, we used data from two previous MRI studies on 32 and 295 healthy individuals, in order to identify first, if the PG shows activations in fMRI and during a memory retrieval task as well as showing functional connectivity with other brain structures, and second, if there are any associations between the PG volume and the memory scores of the individuals. Results: Using a standard PG atlas, our results showed significant activations in PG during memory retrieval, with the strength of these activations increasing with the increment of the cognitive load of the task. Also, PG showed functional connectivity with other brain structures during fMRI, the pattern of which also changed with the cognitive load of the retrieval. Finally, the volume of the PG showed significant associations with the scores of the memory tests. Conclusion: Our knowledge of the PG still needs improvement, and we hope our findings here could be a help for that as well as a help to better understand the mechanisms of memory storage and retrieval in humans. [ABSTRACT FROM AUTHOR]

Papillary tumor of the pineal region (PTPR) is an infrequent neoplasm arising from the ependymal cells of the sub-commissural organ. This tumor entity was incorporated into the World Health Organization (WHO) classification of central nervous system tumors in 2007. Given the propensity for local recurrence observed in PTPR cases and the documented instances of leptomeningeal seeding in previous case reports, it presents a substantial risk of significant morbidity. Due to its rarity, there is no established standard for its management. Surgical intervention constitutes the primary treatment modality, while the role of adjuvant radiotherapy remains ambiguous. In this case report, we present the clinical course of a 46-year-old male diagnosed with PTPR who underwent surgical resection followed by adjuvant radiotherapy. 14 months post-initial treatment, the patient manifested intracranial and spinal metastases in the form of leptomeningeal dissemination. Subsequently, systemic chemotherapy utilizing vincristine and carboplatin was initiated, and the patient exhibited no evidence of disease progression over the last six months.

Objective: To identify the differences between trilateral and quadrilateral retinoblastoma based on radiologic imaging. Case: We found three cases of retinoblastoma at Sanglah General Hospital. The retinoblastoma patients we found were boys under the age of 5. The first patient presented with swelling, pain, and impaired vision in the right eye. The second and third patients presented with eye protrusion and leukocoria. Computed tomography (CT) imaging revealed a calcified mass in the intraorbital region that extended to the cerebral hemispheres. It may be accompanied by hair-on-end periosteal reaction. In the first patient, the mass extended to the pineal gland. In the second and third patients, the mass extended to the suprasellar and pineal regions. Trilateral retinoblastoma consists of a primordial midline neuroectodermal tumor that originates in the pineal or suprasellar region. It is an uncommon combination of unilateral or bilateral retinoblastomas. Quadrilateral retinoblastoma, on the other hand, presents with bilateral retinoblastoma and tumors in both the suprasellar and pineal regions. The histopathology of trilateral and quadrilateral retinoblastoma shows a different pattern from retinoblastoma. Conclusion: Retinoblastoma poses one of the most challenging problems due to its distinct patterns of growth, extension, and recurrence. Intracranial metastasis of trilateral and quadrilateral retinoblastoma exhibits a different pattern. The prognosis and diagnosis of retinoblastoma are significantly influenced by clinical examination, radiologic imaging, and histopathology.