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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]

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]

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]

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]

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]

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]

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]

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]

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 (

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]

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.

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]

Introduction: Multiple sclerosis has a complex pathophysiology, and numerous risk factors can contribute to its development, like exposure to sunlight that is associated with serum levels of melatonin. The aim of this study was to determine whether the volume of the pineal gland, assessed by magnetic resonance imaging (MRI), correlated with the presence of multiple sclerosis. Methods: This retrospective study included a total of 394 patients. Subjects were divided into two groups: the first group consisted of 188 patients with a definite diagnosis of multiple sclerosis (based on revised McDonald criteria) and the second group consisted of 206 healthy controls. To examine the influence of age on pineal gland volume, we stratified the whole sample into three age groups: first involved patients under 20 years, second patients between 20 and 40 years, and third group included patients over 40 years. The maximum length (L) and height (H) of the pineal gland were measured on the T1-weighted sagittal images, and the width (W) was measured on the T2-weighted coronal or axial images. The volume of the gland was calculated as an approximation to an ellipse, according to the formula V = (L × H × W)/2. Results: Pineal gland volume of female multiple sclerosis (MS) patients (N = 129) was significantly lower than in healthy females (N = 123) (p = 0.013; p < 0.05), unlike in males where there is not such difference. Also, pineal gland volume is not age-dependent, and the observed smaller pineal gland in MS patients can reliably be attributed to the disease itself. Additionally, large pineal gland size, especially over 62.83 mm³ when compared to pineal gland volume below 31.85mmmm³ is associated with more than double reduced risk of multiple sclerosis (OR 0.42; p = 0.003). Discussion: Our results suggest that women with multiple sclerosis have smaller pineal glands that can theoretically be explained by a lack of input stimuli and the resultant decrease in gland volume. Additionally, the risk of multiple sclerosis is reduced in larger pineal gland volumes. [ABSTRACT FROM AUTHOR]

This article discusses data showing that mammals, including humans, have two sources of melatonin that exhibit different functions. The best-known source of melatonin, herein referred to as Source #1, is the pineal gland. In this organ, melatonin production is circadian with maximal synthesis and release into the blood and cerebrospinal fluid occurring during the night. Of the total amount of melatonin produced in mammals, we speculate that less than 5% is synthesized by the pineal gland. The melatonin rhythm has the primary function of influencing the circadian clock at the level of the suprachiasmatic nucleus (the CSF melatonin) and the clockwork in all peripheral organs (the blood melatonin) via receptor-mediated actions. A second source of melatonin (Source # 2) is from multiple tissues throughout the body, probably being synthesized in the mitochondria of these cells. This constitutes the bulk of the melatonin produced in mammals and is concerned with metabolic regulation. This review emphasizes the action of melatonin from peripheral sources in determining re-dox homeostasis, but it has other critical metabolic effects as well. Extrapineal melatonin synthesis does not exhibit a circadian rhythm and it is not released into the blood but acts locally in its cell of origin and possibly in a paracrine matter on adjacent cells. The factors that control/influence melatonin synthesis at extrapineal sites are unknown. We propose that the concentration of melatonin in these cells is determined by the subcellular redox state and that melatonin synthesis may be inducible under stressful conditions as in plant cells. [ABSTRACT FROM AUTHOR]

Stroke and Alzheimer's disease (AD) are prevalent age-related diseases; however, the relationship between these two diseases remains unclear. In this study, we aimed to investigate the ability of melatonin, a hormone produced by the pineal gland, to alleviate the effects of ischemic stroke leading to AD by observing the pathogenesis of AD hallmarks. We utilized SH-SY5Y cells under the conditions of oxygen–glucose deprivation (OGD) and oxygen-glucose deprivation and reoxygenation (OGD/R) to establish ischemic stroke conditions. We detected that hypoxia-inducible factor-1α (HIF-1α), an indicator of ischemic stroke, was highly upregulated at both the protein and mRNA levels under OGD conditions. Melatonin significantly downregulated both HIF-1α mRNA and protein expression under OGD/R conditions. We detected the upregulation of β-site APP-cleaving enzyme 1 (BACE1) mRNA and protein expression under both OGD and OGD/R conditions, while 10 µM of melatonin attenuated these effects and inhibited beta amyloid (Aβ) production. Furthermore, we demonstrated that OGD/R conditions were able to activate the BACE1 promoter, while melatonin inhibited this effect. The present results indicate that melatonin has a significant impact on preventing the aberrant development of ischemic stroke, which can lead to the development of AD, providing new insight into the prevention of AD and potential stroke treatments. [ABSTRACT FROM AUTHOR]

Melatonin is a neurohormone synthesized from dietary tryptophan in various organs, including the pineal gland and the retina. In the pineal gland, melatonin is produced at night under the control of the master clock located in the suprachiasmatic nuclei of the hypothalamus. Under physiological conditions, the pineal gland seems to constitute the unique source of circulating melatonin. Melatonin is involved in cellular metabolism in different ways. First, the circadian rhythm of melatonin helps the maintenance of proper internal timing, the disruption of which has deleterious effects on metabolic health. Second, melatonin modulates lipid metabolism, notably through diminished lipogenesis, and it has an antidiabetic effect, at least in several animal models. Third, pharmacological doses of melatonin have antioxidative, free radical‐scavenging, and anti‐inflammatory properties in various in vitro cellular models. As a result, melatonin can be considered both a circadian time‐giver and a homeostatic monitor of cellular metabolism, via multiple mechanisms of action that are not all fully characterized. Aging, circadian disruption, and artificial light at night are conditions combining increased metabolic risks with diminished circulating levels of melatonin. Accordingly, melatonin supplementation could be of potential therapeutic value in the treatment or prevention of metabolic disorders. More clinical trials in controlled conditions are needed, notably taking greater account of circadian rhythmicity. [ABSTRACT FROM AUTHOR]

Background: Melatonin is synthesized from the tryptophan amino acid in the pineal gland. Its role in sleep has been confirmed in other studies. Several studies have also shown the effect of melatonin on postoperative pain and sedation. This study aimed to evaluate the effect of melatonin on postoperative pain in patients undergoing appendectomy. Methods: In a double-blind clinical trial, 64 patients aged 18–50 years with ASA I/II anesthesia class who were candidates for appendectomy with general anesthesia were enrolled. The patients were randomly divided into two groups: melatonin and placebo (32 people in each group). The first group received 6 mg of oral melatonin one hour before sleep, while the second group received a placebo. Before surgery and 2, 12, and 24 hours after surgery, patients’ pain was measured using the Visual Analogue Scale (VAS). The Ramsay sedation score measured the patients’ sedation, and rescue analgesia was measured at the above time points. SPSS software was used to analyze the data, and P-values<0.05 were considered significant. Results: Our study showed that pain levels in the melatonin group were lower at the 2nd, 12th, and 24th hours after the appendectomy surgery than in the placebo group. Sedation rates were not significantly different between the two groups. Analgesic consumption was lower in the melatonin group than in the placebo group. Conclusion: Melatonin can reduce the degree of pain (VAS) after appendectomy. [ABSTRACT FROM AUTHOR]

Background: Pure germinomas account for 40% of pineal tumors and are characterized by the lack of appreciable tumor markers, thus requiring a tumor biopsy for diagnosis. MicroRNAs (miRNA) have emerged as potential noninvasive biomarkers for germ cell tumors and may facilitate the non-invasive diagnosis of pure pineal germinomas. Material and methods: A retrospective chart review was performed on all patients treated at the Children’s Cancer Hospital Egypt diagnosed with a pineal region tumor between June 2013 and March 2021 for whom a research blood sample was available. Plasma samples were profiled for miRNA expression, and DESeq2 was used to compare between pure germinoma and other tumor types. Differentially expressed miRNAs were identified. The area under the curve of the receive;r operating characteristic curve was constructed to evaluate diagnostic performance. Results: Samples from 39 pediatric patients were available consisting of 12 pure germinomas and 27 pineal region tumors of other pathologies, including pineal origin tumors [n = 17; pineoblastoma (n = 13) and pineal parenchymal tumors of intermediate differentiation (n = 4)] and others [n = 10; low-grade glioma (n = 6) and atypical teratoid rhabdoid tumor (n = 4)]. Using an adjusted p-value <0.05, three miRNAs showed differential expression (miR-143-3p, miR-320c, miR-320d; adjusted p = 0.0058, p = 0.0478, and p = 0.0366, respectively) and good discriminatory power between the two groups (AUC 90.7%, p < 0.001) with a sensitivity of 25% and a specificity of 100%. Conclusion: Our results suggest that a three-plasma miRNA signature has the potential to non-invasively identify pineal body pure germinomas which may allow selected patients to avoid the potential surgical complications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Periprosthetic osteolysis is the most common long-term complication of total joint arthroplasty. Many studies suggest that the inflammasome may play an important role during the osteolysis. Melatonin is a rhythm-regulated hormone secreted by the pineal gland with many functions including antiinflammatory, anti-oxidation, and antitumor, but its effects on osteolysis and inflammasome have yet to be explored. OBJECTIVE: To explore the effect of melatonin on the osteolysis induced by wear particles and the role of melatonin on the activation of NLRP3 inflammasome. METHODS: (1) In vivo test: Fifteen C57BL/6 mice were randomly divided into sham operation group, osteolysis group and melatonin group by random number table method, with 5 mice in each group. The osteolysis model of the osteolysis group and the melatonin group was established by injecting cobalt-chromiummolybdenum (CoCrMo) particles into the sagittal suture of the skull. After injection, the melatonin group was intraperitoneally injected with 50 mg/(kg•d) of melatonin for 14 consecutive days. After drug intervention, the mouse calvarium was collected for micro-CT analysis to observe the micro-structural changes around the sagittal suture. (2) In vitro test: Mouse bone marrow-derived macrophages and THP-1 cells (which had been induced to differentiate into macrophages) were taken and divided into seven groups: normal group, lipopolysaccharide group, lipopolysaccharide+CoCrMo group and melatonin 0.5, 1, 1.5, 2 mmol/L groups (lipopolysaccharide and CoCrMo were added to the melatonin intervention groups). After the intervention for 6 hours, the expression of related proteins (NLRP3, Caspase-1, interleukin-1β, and gasdermin D, gasdermin D-N terminal) in the inflammasome of cell lysate or cell culture supernatant was detected by western blot assay. Cytotoxicity and cell death were observed through lactate dehydrogenase release and live-dead fluorescence staining. RESULTS AND CONCLUSION: (1) In vivo test: Micro-CT scanning 3D reconstruction images showed that the bone mass around the sagittal suture of the skull of mice in the osteolysis group was significantly reduced, and the bone tissue structure was severely damaged. Compared with the osteolysis group, the bone mass around the sagittal suture of the skull in the melatonin group was significantly increased, and the destruction of tissue structure was reduced. (2) In vitro test: For mouse bone marrow-derived macrophages, lipopolysaccharide significantly up-regulated NLRP3 protein expression in cell lysate, and melatonin intervention could reduce NLRP3 protein expression in a dose-dependent manner. CoCrMo particles significantly up-regulated the protein expressions of the gasdermin D-N terminal in cell lysate and Caspase-1 and interleukin-1β in the supernatant of cell culture, while melatonin intervention could reduce the expression of these proteins in a dose-dependent manner. For THP-1 cells, the protein expressions of Caspase-1 and interleukin-1β in the supernatant of cell culture were significantly up-regulated by CoCrMo particles, and the expression of these proteins was decreased dose-dependent by melatonin intervention. Lactate dehydrogenase release and live-dead fluorescence staining showed that CoCrMo particles significantly increased the release of lactate dehydrogenase and cell death in the supernatant of mouse bone marrow-derived macrophage culture, and melatonin intervention could reduce the release of lactate dehydrogenase and cell death. (3) The results show that melatonin can inhibit particle-induced inflammasome activation and pyroptosis to suppress periprosthetic osteolysis. [ABSTRACT FROM AUTHOR]

Introduction: Melatonin (MEL) is a crucial neuroendocrine hormone primarily produced by the pineal gland. Pinealectomy (PINX) has been performed on an endogenous MEL deficiency model to investigate the functions of pineal MEL and its relationship with various diseases. However, the eect of PINX on the gastrointestinal tract (GIT) MEL levels and gut microbiome in pigs has not been previously reported. Methods: By using a newly established pig PINX model, we detected the levels of MEL in the GIT by liquid chromatography–tandem mass spectrometry. In addition, we examined the eects of PINX on the expression of MEL synthesis enzymes, intestinal histomorphology, and the intestinal barrier. Furthermore, 16S rRNA sequencing was performed to analyze the colonic microbiome. Results: PINX reduced serum MEL levels but did not aect GIT MEL levels. Conversely, MEL supplementation increased MEL levels in the GIT and intestinal contents. Neither PINX nor MEL supplementation had any effect on weight gain, organ coefficient, serum biochemical indexes, or MEL synthetase arylalkyl amine N-acetyltransferase (AANAT) expression in the duodenum, ileum, and colon. Furthermore, no significant dierences were observed in the intestinal morphology or intestinal mucosal barrier function due to the treatments. Additionally, 16S rRNA sequencing revealed that PINX had no significant impact on the composition of the intestinal microbiota. Nevertheless, MEL supplementation decreased the abundance of Fibrobacterota and increased the abundance of Actinobacteriota, Desulfobacterota, and Chloroflexi. Conclusion: We demonstrated that synthesis of MEL in the GIT is independent of the pineal gland. PINX had no influence on intestinal MEL level and microbiota composition in pigs, while exogenous MEL alters the structure of the gut microbiota. [ABSTRACT FROM AUTHOR]

Objective: The bibliometric perspective examines publications using a quantitative way and statistics to analyze them. The purpose of the current study was to perform a comprehensive overview of the research on the pineal gland through bibliometric methods to determine the trends and rare topics related to the gland. Methods: The Web of Science database was used to identify the publications associated with the gland. The literature review exposed a total of 8719 publications. The identified publications were analyzed using the bibliometric approaches (VOSviewer Version 1.6.13). Results: The first studies on the pineal gland were in the 1970s. The most prolific country is the United States (2451). It was seen that most of the articles were published in Journal of Pineal Research. The majority of publications (97.09%) were written in English. The most prolific author is Reiter, Russel J. Moreover, the most prolific institute is the Centre National De La Recherche Scientifique (France). The most popular keywords in the articles were pineal gland, melatonin, circadian rhythm, rat, retina, photoperiod, circadian, aging, serotonin, oxidative stress, and brain. Conclusion: The results indicated the researchers’ interest in the gland and provided quantitative data about the place of the gland in the scientific area. Studies on this subject have tended to increase in recent years. As far as we know, this research is the first bibliometric study to provide a comprehensive analysis of scientific publications with an emphasis on the pineal gland since 1976. [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. [ABSTRACT FROM AUTHOR]

Melatonin is a pleiotropic neurohormone found in different animal, plant, and microorganism species. It is a product resulting from tryptophan metabolism in the pineal gland and is widely known for its ability to synchronize the circadian rhythm to antitumor functions in different types of cancers. The molecular mechanisms responsible for its immunomodulatory, antioxidant and cytoprotective effects involve binding to high-affinity G protein-coupled receptors and interactions with intracellular targets that modulate signal transduction pathways. In vitro and in vivo studies have reported the therapeutic potential of melatonin in different infectious and parasitic diseases. In this review, the protective and pathophysiological roles of melatonin in fighting protozoan and helminth infections and the possible mechanisms involved against these stressors will be discussed. • Melatonin is an indole hormone with different functions, from antioxidant activity to immunomodulation. • Melatonin has activity against protozoa by acting, above all, directly and indirectly in the infectious process. • Melatonin reduces the impact of the infectious process caused by helminths, especially by inducing protection against oxidative stress. [ABSTRACT FROM AUTHOR]

Acute HSV-1 infection is associated with mild symptoms, such as fever and lesions of the mouth, face and skin. This phase is followed by a latency period before reactivation, which is associated with symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, the development of new antiviral agents is sought due to the presence of resistant viruses. Melatonin, a molecule secreted by the pineal gland, has been shown to be an antioxidant, inducer of antioxidant enzymes, and regulator of various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. This study focuses on melatonin's role in HSV-1 replication and the underlying mechanisms. Melatonin was found to decrease the synthesis of HSV-1 proteins in infected Vero cells measured by immunofluorescence, indicating an inhibition of HSV-1 replication. Additionally, it regulates the activities of antioxidant enzymes and affects proteasome activity. Melatonin activates the unfolded protein response (UPR) and autophagy and suppresses apoptosis in HSV-1-infected cells. In summary, melatonin demonstrates an inhibitory role in HSV-1 replication by modulating various cellular responses, suggesting its potential utility in the treatment of viral infections. [ABSTRACT FROM AUTHOR]

Homeobox genes encode transcription factors that are widely known to control developmental processes. This is also the case in the pineal gland, a neuroendocrine brain structure devoted to nighttime synthesis of the hormone melatonin. Thus, in accordance with high prenatal gene expression, knockout studies have identified a specific set of homeobox genes that are essential for development of the pineal gland. However, as a special feature of the pineal gland, homeobox gene expression persists into adulthood, and gene product abundance exhibits 24 h circadian rhythms. Recent lines of evidence show that some homeobox genes even control expression of enzymes catalyzing melatonin synthesis. We here review current knowledge of homeobox genes in the rodent pineal gland and suggest a model for dual functions of homeobox gene‐encoded transcription factors in developmental and circadian mature neuroendocrine function. [ABSTRACT FROM AUTHOR]

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.

A rare type of brain tumor, pineoblastoma (PNET) is found in young adults and children. PNETs are rarest representing under 1% of all cerebrum cancers. The most common type of this type of tumor starts at the pineal glands, a small gland located at the base of the brain. Pineoblastomas make up approximately 50% of all pineal gland tumors. These tumors can be challenging to treat because of their location in the brain. The five-year endurance of patients of PNETs or pineoblastoma is around 50-60%. Infants and children who have had partial surgical removal and a poor response to radiation therapy have less favorable outcomes.

Background. Involved in many cascades of biological regulatory reactions, calcium, vitamin D and melatonin create a single metabolic pattern, maintaining the dynamic balance of bone tissue homeostasis. Nevertheless, these regulatory molecules, as structural and functional elements of bone tissue, play a crucial role in various cellular processes associated with oncogenesis and tumor progression. Synthetic peptide dalargin has wound healing, reparative, anti-inflammatory, antioxidant, immunomodulatory, anticarcinogenic, antitumor, and antimetastatic effects. The purpose of the study was to investigate the synthetic neuropeptide dalargin influence on the dynamics of vitamin D and melatonin blood serum le­vels as part of the treatment algorithm of patients with bone malignant tumors of the lower extremities and pelvis with polymorbidity and endoprosthetics. Materials and methods. The study inclu­ded a control (first) group and a main (second) group of clinical observation of patients with malignant bone lesions. The serum melatonin content was measured by enzyme immunoassay using reagent kits (No. RE54021) from IBL-Hamburg GmbH (Germany). Serum levels of 25-hydroxycalciferol (25(OH)D) were determined by the immunochemiluminescent method on an ARCHITECT 25-OH Vitamin D Controls automatic analyzer. Results. In patients who received dalargin, more pronounced positive dynamics were established in the normalization of 25(ОН)D and melatonin levels, and there was no exacerbation of concomitant diseases. In contrast to the data of patients who did not receive dalargin, in the group where it was used, there were no relapses or metastases of the tumor du­ring 14 months. A comparison of the 25(ОН)D and melatonin le­vels in patients 6–7 months and 12–14 months after treatment shows a tendency to recovery of indicators only in patients who were additionally treated with dalargin (p < 0.01). Conclusions. The study showed the possibility of using the neuropeptide dalargin to increase the effectiveness of the treatment of patients with primary malignant tumors with the burden of polymorbidity by influencing the levels of vitamin D and melatonin in the blood serum.