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Background: The formation of concrements in human pineal gland (PG) is a physiological process and, according to many researchers, is associated with the involution of PG structures. The majority of scientific publications concern progressive calcification of PG, leaving out studies on the destruction of already formed calcified concrements. Our study fills the gap in knowledge about calcified zones destruction in PG in normal aging and neuropathological conditions, which has not been addressed until now. Purpose: Our objective is to gain insight into human PG tissue impairment in both normal aging and neurodegenerative conditions. X-ray phase-contrast tomography (XPCT) allowed us to study PG tissue degeneration at high spatial resolution and, for the first time, to examine the damaged PG concrements in detail. Our research finding could potentially enhance the understanding of the PG involvement in the process of aging as well as in Alzheimer’s disease (AD) and vascular dementia (VD). Methods: The research was carried out on human PG autopsy material in normal aging, VD, and AD conditions. Laboratory-based micro-computed tomography (micro-CT) was used to collect and evaluate samples of native, uncut, and unstained PG with different degrees of pineal calcification. The detailed high-resolution 3D images of the selected PGs were produced using synchrotron-based XPCT. Histology and immunohistochemistry of soft PG tissue confirmed XPCT results. Results: We performed via micro-CT the evaluation of the morphometric parameters of PG such as total sample volume, calcified concrements volume, and percentage of concrements in the total volume of the sample.XPCT imaging revealed high-resolution details of age-related PGalteration.In particular,we noted signs of moderate degradation of concrements in some PGs from elderly donors. In addition, our analysis revealed noticeable degenerative change in both concrements and soft tissue of PGs with neuropathology. In particular, we observed a hollow core and separated layers as well as deep ragged cracks in PG concrements of AD and VD samples. In parenchyma of some samples,we detected wide pinealocyte-free fluid-filled areas adjacent to the calcified zones. Conclusion: The present work provides the basis for future scientific research focused on the dynamic nature of PG calcium deposits and PG soft tissue in normal aging and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive type of skin cancer, with a greater risk of metastasis and a higher prevalence and mortality rate. This cancer type has been demonstrated to develop resistance to the known treatment options such as conventional therapeutic agents and targeted therapy that are currently being used as the standard of care. Drug repurposing has been explored as a potential alternative treatment strategy against disease pathophysiologies, including melanoma. To that end, multiple studies have suggested that melatonin produced by the pineal gland possesses anti-proliferative and oncostatic effects in experimental melanoma models. The anticarcinogenic activity of melatonin is attributed to its ability to target a variety of oncogenic signaling pathways, including the MAPK pathways which are involved in regulating the behavior of cancer cells, including cell survival and proliferation. Additionally, preclinical studies have demonstrated that melatonin in combination with chemotherapeutic agents exerts synergistic effects against melanoma. The goal of this review is to highlight the mechanistic insights of melatonin as a monotherapy or combinational therapy for melanoma treatment. [ABSTRACT FROM AUTHOR]

Background: Several experimental intents require pineal gland removal. The main challenge of the pinealectomy surgical procedure is the hemorrhage due to the transverse sinus torn. The study aimed to modify the rat pinealectomy surgical procedure to reduce the risk of bleeding and the mortality rate. Methods: Adult male rats experienced pinealectomy surgery. A mini-drill was used to remove a small skull area in the junction of the lambda and sagittal sutures. The pineal gland was removed using a curved-head hook. Animals experienced intensive post-surgical care. Locomotion, cerebellar motor function, working memory, and anxiety were evaluated 2 weeks after pinealectomy by the open field, rotarod, Y maze, and the elevated plus maze, respectively. Results: Surgical modification reduced the bleeding risk and animal mortality rate. No significant alteration was found in locomotion and working memory. However, the pinealectomy was anxiogenic and decreased entry to the open arm. The cerebellar motor performance did not change in the rotarod test. Hematoxylin–Eosin staining of removed tissue confirmed the histology of the pineal gland. Conclusion: Advantages of this technique were removing a small skull area, modifying the hook insertion point to prevent damaging the brain veins, reducing the bleeding risk and the mortality rate. Surgery modification was associated with a decreased final number of animals used. Regardless of the melatonin shortage, pinealectomy affects different organs, which should be considered in the research study design. [ABSTRACT FROM AUTHOR]

In this work, we report preliminary results about the involution of the human pineal gland involution. The detailed analysis of pineal structure was done on autopsy material of 77 persons in age 27–96 using x-ray phase-contrast tomography, histology, and immunohistochemistry. Our study suggests that the pineal gland alteration in older adults may be more profound than has been reported to date. We identified and described a new form of pineal gland involution that eventually led to the total degradation of the pineal gland. To our knowledge, this study is the first to report on the complete replacement of pineal gland parenchyma with connective tissue in older adults. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Psychosomatische Medizin und Psychotherapie is the property of Vandenhoeck & Ruprecht GmbH & Co. KG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ABSTRACT The pineal is a neuroendocrine gland responsible for the synthesis and release of melatonin. It is present in the brain of vertebrates, but its morphology and location vary considerably among species. For the species Alouatta belzebul, although some anatomical aspects of the nervous system have been described, there is no information on the morphology and histological composition of this gland. Thus, the present study aimed to describe the morphological, morphometric, and histological aspects of the pineal of Alouatta belzebul. Seven adult specimens were dissected from which the location of the gland in relation to the surrounding brain structures was described, and its length and width were measured. Histological slides were then prepared and stained using hematoxylin-eosin and PAS techniques. It was observed that the pineal of Alouatta belzebul is located superior and cranial to the cerebellum, superior to the superior colliculi and below the splenium of the corpus callosum and was classified as sub-callosal. It had an average length of 2.6mm and an average width of 1.14mm. Histologically the gland is composed of irregular strands of pinealocytes and gliocytes. The pinealocytes showed pigments similar to melanin.

This article discusses the use of oral melatonin as a treatment for recalcitrant melasma, a common hyperpigmentary disorder. The study reports on a series of seven cases in which patients with melasma were treated with a 3mg melatonin tablet once daily for 12 weeks, along with the use of broad-spectrum sunscreen. After the treatment period, all patients reported lightening of pigmentation and a decrease in the severity of melasma. No side effects were reported. The article concludes that melatonin is a safe and effective treatment option for melasma, but further research is needed to fully understand its potential. [Extracted from the article]

Introduction: Melatonin is a well-known drug and dietary supplement that is steadily growing in popularity on the pharmaceutical market. This indolamine, which has been known for more than 50 years, is produced by the pineal gland depending on the circadian rhythm. Also referred to as the "darkness hormone" and secreted mainly during nighttime hours, it is primarily associated with the treatment of sleep-wake rhythm disorders or disorders associated with sudden shifting time zones (jet lag). However, many scientific studies have shown that melatonin has multidirectional effects. It is used both as a chronobiotic, i.e., a drug that regulates circadian rhythms, as well as having anti-inflammatory, anti-oxidative, and anti-carcinogenic properties, regulating mitochondrial function, and affecting many systems and organs, keeping the organism in a state of homeostasis. Purpose: This review article aims to provide an overview of the mechanism of action of melatonin, its current indications in clinical practice, and potential future directions for therapy use. Materials and methods: A summary of reports available in publications and scientific studies posted in medical information databases: Pubmed, CrossRef, Google Scholar, and book positions. Results: The pleiotropic effect of melatonin can be used as an supportive drug in the treatment of sleep disorders, disorders of the central nervous system, the cardiovascular system, the gastrointestinal system, and many oncological diseases. Conclusions: Despite a number of important reports on the positive effects of melatonin in the treatment of disorders in many areas of medicine, it is necessary to deepen research with its participation and the emergence of recommendations for its use in order to safely introduce the drug into common clinical practice.

Spinal cord injury (SCI) damages multiple structures at the lesion site, including ascending, descending, and propriospinal axons; interrupting the conduction of information up and down the spinal cord. Additionally, axons associated with the autonomic nervous system that control involuntary physiological functions course through the spinal cord. Moreover, sympathetic, and parasympathetic preganglionic neurons reside in the spinal cord. Thus, depending on the level of an SCI, autonomic function can be greatly impacted by the trauma resulting in dysfunction of various organs. For example, SCI can lead to dysregulation of a variety of organs, such as the pineal gland, the heart and vasculature, lungs, spleen, kidneys, and bladder. Indeed, it is becoming more apparent that many disorders that negatively affect quality-of-life for SCI individuals have a basis in dysregulation of the sympathetic nervous system. Here, we will review how SCI impacts the sympathetic nervous system and how that negatively impacts target organs that receive sympathetic innervation. A deeper understanding of this may offer potential therapeutic insight into how to improve health and quality-of-life for those living with SCI. [ABSTRACT FROM AUTHOR]

The Pineal gland (PG) is the site of production of melatonin as an important central hormone in the body. It is not known yet whether PG calcification (PGC) is an age-associated physiological process or a pathologic condition caused by lifestyle-factors and metabolic-dysregulations. Here, we performed a cross-sectional analysis on 586 patients referred to have Computed Tomographic (CT) scans (above 15 years old), in the Ali Ebne Abi Taleb hospital radiology center in 2017–2018. Based on the CT-scans of the brain, the presence of PGC was recorded and a score of scale 0 to 6 (PGC_score) was calculated for its intensity based on the volume and the Hounsfield units of the calcified pineal. Logistic and ordered logistic regression tests were employed to determine potential risk factor of PGC and higher PGC_score, respectively, testing the factors age, sex, history of cardiovascular and metabolic diseases, smoking and opioid use. We found male sex (OR: 2.30 (95% CI:1.39–3.82) and smoking cigarettes (OR: 4.47 (95% CI:1.01–19.78)) as the main potential risk factors for the pineal gland calcification. For PGC_score, we found age to be dose-dependently associated with PGC_score only in patients aged below 63 (p-trend < 0.001). Stratifying for age, in patients < 63 years old, we found age, male sex (positive association) and dyslipidemia (negative association) as the main significantly associated factors of PGC_score. On the contrary, in patients aged > = 63, cigarette smoking was the only significantly associated factor of higher PGC_score. In conclusion, our results indicate that at ages below 63, age, male sex and blood lipid are the main associated factors of higher PGC, but at ages above that, the lifestyle factor smoking is significantly associated with higher pineal gland calcification. [ABSTRACT FROM AUTHOR]

To investigate the utility of melatonin supplementation as a treatment option for individuals with sleep disturbance after traumatic brain injury (TBI). A systematic search was conducted in 6 electronic databases (Medline, AMED, CINAHL, Embase, Scopus, and SPORTDiscus) from earliest records to April 2022. Studies were eligible for inclusion if they met the following criteria: a) human participants with sleep disturbance after TBI, b) melatonin or melatonergic agent used as an intervention to treat sleep disturbance, and c) outcomes of melatonin administration reported. All TBI severity types (mild, moderate, and severe) were eligible. The initial search retrieved a total of 595 articles, with 9 studies meeting the eligibility criteria. Two reviewers independently extracted data from eligible studies and assessed methodological quality. Extracted data consisted of participant and injury characteristics, melatonin interventional properties, and sleep outcome. Methodological quality was assessed via the Downs and Black checklist. A total of 251 participants with TBI-induced sleep disturbance (mean age range: 14.0-42.5 years) were included. Melatonin, Circadin (prolonged-release melatonin), or Ramelteon (melatonin receptor agonist) were administered. Dosages and intervention duration ranged from 2 to 10 mg and 3 to 12 weeks, respectively. Eight out of 9 studies reported positive outcomes after melatonin treatment. Significant improvements in subjective sleep quality, objective sleep efficiency, and total sleep time were found with melatonin. Reductions in self-reported fatigue, anxiety, and depressive symptoms were also observed with melatonin treatment. No serious adverse events were reported after melatonin administration. Melatonin has good tolerability after short-term use and the potential to be a therapeutic agent for those with sleep disturbance after TBI. Melatonin was shown to be beneficial to sleep quality, sleep duration, and sleep efficiency. Additional clinically relevant outcomes of improved mental health suggest that melatonin use may be a promising treatment option for individuals experiencing co-occurring disorders of mood and sleep disturbance post-injury. [ABSTRACT FROM AUTHOR]

Circadian rhythmicity is an autonomous period of organ cells’ functioning that is controlled by feedback mechanisms and specific genes. The thyroid gland, as a peripheral organ of the endocrine system, is subordinate to the adenohypophysis and pineal gland. Melatonin, as one of the main mediators of circadian influence, is well known for its antitumor and regulatory effects on a number of tissues, but its relationship with the hormone-producing activity of the thyroid gland has not been sufficiently studied. The purpose of the work was to analyze the current data on circadian regulation of the thyroid gland by examining evidence-based scientific publications from open databases over the past five years. Melatonin-producing pineal cells possess the homeotic genes Otx2 and Crx whose deactivation leads to a significant decrease in melatonin production by the pineal gland. In addition to pineal cells, melatonin can be synthesized by adenohypophysis-independent parafollicular cells. The effect of melatonin on thyrocytes is provided by binding to MT1 receptors and affecting the expression of thyroglobulin, RX-8, and TTF-1 (NKX2-1) genes. Under conditions of short photoperiod, melatonin inhibits the production of thyroid-stimulating hormone (TSH) β, which, in turn, acts on hypothalamic tanycytes by regulating the balance of deiodinase (Dio2/Dio3). This leads to a well-regulated seasonal control of the release of the thyroid hormone triiodothyronine. Conclusions. Circadian regulation of thyrocyte activity occurs under the influence of melatonin, which is secreted by pinealocytes and sometimes by parafollicular cells. TSH is secreted with a certain circadian periodicity under the influence of the activation of chronorhythmic genes. Hormone replacement therapy should be aimed not only at restoring the levels of pituitary hormones, but also at restoring the biological rhythm of TSH secretion. Melatonin affects the circadian work of thyrocytes, which is proven by determining the expression of the chronorhythm genes Bmal-1, Dio2, TTF-1. In thyroid pathology, there is a violation of circadian rhythms, a decrease in melatonin levels, and a decrease in the expression of Clock genes. [ABSTRACT FROM AUTHOR]

As people age, their risks of developing degenerative diseases such as cancer, diabetes, Parkinson's Disease (PD), Alzheimer's Disease (AD), rheumatoid arthritis, and osteoporosis are generally increasing. Millions of people worldwide suffer from these diseases as they age. In most countries, neurodegenerative diseases are generally recognized as the number one cause afflicting the elderly. Endoplasmic reticulum (ER) stress has been suggested to be associated with some human neurological diseases, such as PD and AD. Melatonin, a neuroendocrine hormone mainly synthesized in the pineal gland, is involved in pleiotropically biological functions, including the control of the circadian rhythm, immune enhancement, and antioxidant, anti-aging, and anti-tumor effects. Although there are many papers on the prevention or suppression of diseases by melatonin, there are very few papers about the effects of melatonin on ER stress in neurons and neurodegenerative diseases. This paper aims to summarize and present the effects of melatonin reported so far, focusing on its effects on neurons and neurodegenerative diseases related to ER stress. Studies have shown that the primary target molecule of ER stress for melatonin is CHOP, and PERK and GRP78/BiP are the secondary target molecules. Therefore, melatonin is crucial in protecting neurons and treating neurodegeneration against ER stress. [ABSTRACT FROM AUTHOR]

The circadian clock is a regulatory system, with a periodicity of approximately 24 h, that generates rhythmic changes in many physiological processes. Increasing evidence links chronodisruption with aberrant functionality in clock gene expression, resulting in multiple diseases, including cancer. In this context, tumor cells have an altered circadian machinery compared to normal cells, which deregulates the cell cycle, repair mechanisms, energy metabolism and other processes. Melatonin is the main hormone produced by the pineal gland, whose production and secretion oscillates in accordance with the light:dark cycle. In addition, melatonin regulates the expression of clock genes, including those in cancer cells, which could play a key role in the numerous oncostatic effects of this hormone. This review aims to describe and clarify the role of clock genes in cancer, as well as the possible mechanisms of the action of melatonin through which it regulates the expression of the tumor's circadian machinery, in order to propose future anti-neoplastic clinical treatments. [ABSTRACT FROM AUTHOR]

Intracranial and spinal epidermoids are benign slow‐growing congenital lesions. They are predominantly intradural, extra‐axial in location, with intra‐axial locations (intra‐parenchymal and spinal intramedullary) being rare. The most common locations of intradural epidermoids are cerebellopontine angle cistern followed by supra‐ and para‐sellar regions, and fourth ventricle. Less common locations include inter‐hemispheric fissure, sylvian fissure, lateral ventricle, intracerebral, velum interpositum cistern, superior cerebellar cistern and pineal gland. They can also be extradural, usually arising in the diploic space of the calvaria, though they are less common. Magnetic resonance imaging is the primary modality for diagnosis and knowing the extent of the lesion. In this pictorial review, we intend to illustrate their classical and unusual locations, atypical imaging findings including calcifications, rare complications like haemorrhage or spontaneous rupture. [ABSTRACT FROM AUTHOR]

The Mediterranean diet (MD) has beneficial effects on human health, which is evidenced by the observation of lower incidence rates of chronic diseases in Mediterranean countries. The MD dietary pattern is rich in antioxidants, such as melatonin, which is a hormone produced mainly by the pineal gland and controls several circadian rhythms. Additionally, melatonin is found in foods, such as fruit and vegetables. The purpose of this systematic review was to assess the melatonin content in Mediterranean foods and to evaluate the influence of the MD on melatonin levels in both humans and model organisms. A comprehensive search was conducted in four databases (PubMed, Scopus, Cochrane Library and Web of Science) and data were extracted. A total of 31 records were chosen. MD-related foods, such as tomatoes, olive oil, red wine, beer, nuts, and vegetables, showed high melatonin contents. The consumption of specific MD foods increases melatonin levels and improves the antioxidant status in plasma. [ABSTRACT FROM AUTHOR]

The pineal gland is integral to the circadian timing system due to its role in nightly melatonin production. Retinoic acid (RA) is a potent regulator of gene transcription and has previously been found to exhibit diurnal changes in synthesis and signalling in the rat pineal gland. This study investigated the potential for the interaction of these two systems. PCR was used to study gene expression in mouse and human pineal glands, ex-vivo organotypic cultured rat pineal gland and cell lines. The mouse and human pineal glands were both found to express the necessary components required for RA signalling. RA influences the circadian clock in the brain, therefore the short-term effect of RA on clock gene expression was determined in ex vivo rat pineal glands but was not found to rapidly regulate Per1, Per2, Bmal1, or Cry1. The interaction between RA and melatonin was also investigated and, unexpectedly, melatonin was found to suppress the induction of gene transcription by RA. This study demonstrates that pineal expression of the RA signalling system is conserved across mammalian species. There is no short-term regulation of the circadian clock but an inhibitory effect of melatonin on RA transcriptional activity was demonstrated, suggesting that there may be functional cross-talk between these systems. [ABSTRACT FROM AUTHOR]

Copyright of Brazilian Journal of Biology is the property of Instituto Internacional de Ecologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Environmental light exposure is an important factor for human health that impacts the biological clock of organisms. Melatonin usually serves as a chemical expression of darkness since light exposure suppresses its synthesis. The low level of melatonin is associated with a spectrum of disorders since melatonin is a potent endogenous antioxidant; therefore, individuals should avoid visible light exposure at night. However, evidence also shows that near infrared radiation (NIR), which occupies a major portion of the wavelengths of sunlight, promotes melatonin production and the beneficial effects of sun baths or photobiomodulation therapy may be, at least, partially mediated by the increased local melatonin production induced by NIR. Unlike visible light, NIR can penetrate deep into the human body including the muscle, brain, and even the bones, and its effects on human biology remain to be clarified. Thus, the avoidance of light at night and exposure to sun during the day are equally important to improve melatonin production and human well-being. Throughout the history of melatonin research, almost exclusive focus has been on nocturnally-generated pineal melatonin production, which accounts for its circadian rhythm in the blood and cerebrospinal fluid; these light/dark melatonin cycles drive the daily and seasonal photoperiodic alterations in organismal physiology. Because pineal melatonin is produced and secreted primarily at night, it is referred to as the chemical expression of darkness. The importance of the other sources of melatonin has almost been ignored. Based on current evidence, there are at least four sources of melatonin in vertebrates that contribute to the whole-body melatonin pool. These include melatonin produced by (1) the pineal gland; (2) extrapineal cells, tissues, and organs; (3) the microbiota of the skin, mouth, nose, digestive tract, and vagina as well as (4) melatonin present in the diet. These multiple sources of melatonin exhibit differentially regulated mechanisms for its synthesis. Visible light striking the retina or an intense physical stimulus can suppress nocturnal pineal melatonin levels; in contrast, there are examples where extrapineal melatonin levels are increased during heavy exercise in daylight, which contains the whole range of NIR radiation. The cumulative impact of all cells producing augmented extrapineal melatonin is sufficient to elevate sweat concentrations, and potentially, if the exposure is sustained, to also increasing the circulating values. The transient increases in sweat and plasma melatonin support the premise that extrapineal melatonin has a production capacity that exceeds by far what can be produced by the pineal gland, and is used to maintain intercellular homeostasis and responds to rapid changes in ROS density. The potential regulatory mechanisms of near infrared light (NIR) on melatonin synthesis are discussed in detail herein. Combined with the discovery of high levels of melanopsin in most fat cells and their response to light further calls into question pineal centric theories. While the regulatory processes related to microbiota-derived melatonin are currently unknown, there does seem to be crosstalk between melatonin derived from the host and that originating from microbiota. [ABSTRACT FROM AUTHOR]

Endometriosis is a benign gynecological disease characterized by abnormal growth of endometrial‐like cells outside the uterus. Melatonin, a hormone secreted by the pineal gland, has been shown to have therapeutic effects in various diseases, including endometriosis. However, the underlying molecular mechanisms are yet to be elucidated. The results of this study demonstrated that melatonin and dienogest administration effectively reduced surgically induced endometriotic lesions in a mouse model. Melatonin suppressed proliferation, induced apoptosis, and dysregulated calcium homeostasis in endometriotic cells and primary endometriotic stromal cells. Melatonin also caused mitochondrial dysfunction by permeating through the mitochondrial membrane to disrupt redox homeostasis in the endometriotic epithelial and stromal cells. Furthermore, melatonin affected oxidative phosphorylation systems to decrease ATP production in End1/E6E7 and VK2/E6E7 cells. This was achieved through messenger RNA‐mediated downregulation of respiratory complex subunits. Melatonin inhibited the PI3K/AKT and ERK1/2 pathways and the mitochondria‐associated membrane axis and further suppressed the migration of endometriotic epithelial and stromal cells. Furthermore, we demonstrated that tiRNAGluCTC and tiRNAAspGTC were associated with the proliferation of endometriosis and that melatonin suppressed the expression of these tiRNAs in primary endometriotic stromal cells and lesions in a mouse model. Thus, melatonin can be used as a novel therapeutic agent to manage endometriosis. [ABSTRACT FROM AUTHOR]

Melatonin (N-acetyl-5-methoxytryptamine, MEL), secreted by the pineal gland, plays an important role in regulation of various functions in the human body. There is evidence that MEL exhibits antitumor effect in various types of cancer. We studied the combined effect of MEL and drugs from different pharmacological groups, such as cytarabine (CYT) and navitoclax (ABT-737), on the state of the pool of acute myeloid leukemia (AML) tumor cell using the MV4-11 cell line as model. The combined action of MEL with CYT or ABT-737 contributed to the decrease in proliferative activity of leukemic cells, decrease in the membrane potential of mitochondria, and increase in the production of reactive oxygen species (ROS) and cytosolic Ca2+. We have shown that introduction of MEL together with CYT or ABT-737 increases expression of the C/EBP homologous protein (CHOP) and the autophagy marker LC3A/B and decreases expression of the protein disulfide isomerase (PDI) and binding immunoglobulin protein (BIP), and, therefore, could modulate endoplasmic reticulum (ER) stress and initiate autophagy. The findings support an early suggestion that MEL is able to provide benefits for cancer treatment and be considered as an adjunct to the drugs used in cancer therapy. [ABSTRACT FROM AUTHOR]

Purpose: Adolescent idiopathic scoliosis (AIS) is believed to be caused by genetic, neurological, osseous growth anomalies, histological variables including muscle fiber percentage and core structure changes, metabolic and hormonal dysfunction, vestibular dysfunction, and platelet microarchitecture. The objective of this study was to contribute to the determination of the cause of AIS by analyzing the changes in pineal gland volume in AIS cases. Methods: Study (AIS) and control group were each comprised of 26 patients who met the inclusion requirements. Scoliosis radiograph and MRI of the pineal glands were used for radiological examinations. The distribution of age, gender, Risser grading for skeletal radiological development, and sexual maturation according to Tanner categorization were uniform and statistically insignificant between groups. Results: When the pineal gland volumes of the cases were evaluated according to age, the AIS group was found to have significantly reduced pineal gland volumes in all age groups. The pineal gland volume was found to be 38.1% lower in the AIS group compared to the control group (p˂0.001). In the AIS group, patients aged 13 years had the lowest pineal gland volume (77.2 ± 13.86 mm3), while patients aged 15 years had the highest volume (97.9 ± 16.47 mm3). Conclusion: Changes in pineal gland volume support the role of the pineal gland in the etiopathogenesis of AIS. [ABSTRACT FROM AUTHOR]

The pineal gland is a small-sized, photo neuroendocrine organ in the midline of the brain that synthesises and secretes melatonin and serotonin. Chords and islands of pinealocytes constitute the secretory parenchyma, while glial tissue and calcifications represent degenerative changes. This study examined human postmortem pineal glands to microscopically assess morphological changes possibly associated with clinical data, by using digital techniques. A retrospective autopsy study has been performed on 72 paediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with synaptophysin (SYN), neuron-specific enolase (NSE), and neurofilament (NF). Slides were digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. The comorbidities used for correlation with morphometric data were obesity, type 2 diabetes, adrenal gland adenoma, goitre, chronic pancreatitis, arterial hypertension, and mixed dementia. Thirty-three females and 39 males were included in the study. Increased secretory parenchyma was found in patients with chronic pancreatitis, arterial hypertension, and adrenal gland adenoma. Reduced activity was found in patients with type 2 diabetes, obesity, advanced pineal calcification, mixed dementia, and old age. There were no changes associated with goitre, cachexia, or Willis's polygon atherosclerosis. No significant differences between gender were found. The activity of the pineal gland can be assessed by quantitative immunohistochemistry of neuroendocrine and structural pinealocyte markers and observation of glial tissue and calcifications. There is a need for further research to evaluate the clinical impact of these morphological changes on the neuroendocrine systems, with clinical implications in endocrinology, neurology, and even psychiatry. Digital techniques offer a more exact analysis of histological data. [ABSTRACT FROM AUTHOR]

Background: Infertility is the inability of couples to achieve pregnancy after one year of regular unprotected coitus. Infertility is the problem of 15% of young couples in different countries and male factor infertility accounts for 50% of cases. Melatonin or 5-methoxy-N-acetyltryptamine was discovered by Aaron Lerner in 1958 while studying bovine pineal glands. Significant advancements have been made in the research on melatonin, which has revealed its vital roles in regulating sleep-wake cycle rhythms, decelerating the aging process, and functioning as an antioxidant or anti-inflammatory agent. Additionally, melatonin, a critical component in reproductive functions, can eliminate free radicals such as (ROS). Objective: The present study aims to evaluate the impact of Melatonin on male infertility. Materials and methods: Serum melatonin was measured by using the Elabscience ELISA kit. A case-control study included the fertile group as the control (n=40) and the infertile group (n=50). All the subjects were included in this study between October 2022 and June 2023. The diagnosis of the participants was executed by a medical senior based on clinical characteristics, the history of patients, and biochemical tests. Age, family history, and BMI were measured. Blood samples were provided by each participant for the biochemical estimation of serum melatonin, FSH, LH, and testosterone. While semen samples were collected from each participant for the seminal fluid analysis. Results: The results of this study showed a decrease in the level of melatonin in infertile men as compared with fertile men. Moreover, there was no significant correlation between melatonin and FSH, LH, testosterone, and some semen parameters. Conclusions: The study indicated that decreased melatonin levels can be associated with male infertility, but it did not indicate a direct relationship between melatonin and hormone levels or specific semen parameters. [ABSTRACT FROM AUTHOR]

Reproductive seasonality is a limiting factor in sheep production. Sexual behavior is a key element in reproductive efficiency, and this function is regulated by the hypothalamus-pituitary-gonadal (HPG) axis. To understand the mechanisms of sexual behavior, transcriptomic sequencing technology was used to identify differentially expressed genes (DEGs) in the hypothalamus (HT), pars tuberalis (PT) and pineal gland (PG) in Rasa Aragonesa rams with different sexual behavior. Bioinformatics analysis of the 16,401 identified genes by RNA-Seq revealed 103 and 12 DEGs in the HT and the PG, respectively, at a false discovery rate (FDR) of 5% with an absolute value of expression ≥ 1 (log2FC). However, no DEGs were found in the PT. Functional annotation and pathway enrichment analysis showed that DEGs of HT were enriched mainly in neuroactive ligand-receptor interactions and signaling pathways, including notable candidate genes such as MTNR1A, CHRNA2, FSHB, LHB, GNRHR, AVP, PRL, PDYN, CGA, GABRD, and TSHB , which play a crucial role in sexual behavior. The GnRH and cAMP signaling pathways were also highlighted. In addition, gene set enrichment analysis (GSEA) identified potential pathways, dominated mainly by biological process category, that could be responsible for the differences in sexual behavior observed in rams. The intracellular protein transport and pattern specification process were enriched within the PT and the transcription factor binding and protein ubiquitination pathways for the PG. Thus, these pathways together may play an important role in the regulation of the sexual behavior in Rasa Aragonesa rams through the hypothalamic-pituitary-gonadal axis. The validation of 5 DEGs using reverse transcription quantitative polymerase chain reaction (RT-qPCR) showed expression patterns like the found with RNA-Seq. Overall, these results contribute to understanding the genomic basis of sexual behavior in rams. Our study demonstrates that multiple networks and pathways orchestrate sexual behavior in sheep. [ABSTRACT FROM AUTHOR]

We review the literature on the little-known roles of specific CaMKs in regulating endocrine functions of the pineal gland, the pituitary gland, and the hypothalamus. Melatonin activates hippocampal CaMKII, which then influences dendritogenesis. In the pituitary gland, the signal pathways activated by the CaMK in lower vertebrates, such as fishes, differ from those of mammals. In the teleost anterior pituitary, the activation of CaMKII induces the expression of somatolactin by glucagon b. In rats and humans, CaMKIVs have been associated with gonadotropes and thyrotropes and CaMKII with several types of human tumor cells and with a specific signaling pathway. Neuropeptides such as vasopressin and endothelin are also involved in the CaMKII signaling chain, as is the CaMKIIδ isoform which participates in generating the circadian rhythms of the suprachiasmatic nucleus. What arises from this review is that most of the hypothalamic CaMKs are involved in activities of the endocrine brain. Furthermore, among the CaMKs, type II occurs with the highest frequency followed by CaMKIV and CaMKI. [ABSTRACT FROM AUTHOR]

Melatonin, a naturally biosynthesized molecule secreted by the pineal gland, exhibits antitumor activities against several different types of cancer. The mechanisms of action of melatonin against tumor progression involve cellular apoptosis, antimetastatic activity, antioxidant and mutagenic effects, antiangiogenic activity, and the restoration of cancer immune surveillance. Melatonin has anticancer activity when administered alone or in combination with standard chemotherapeutic agents, with measurable improvements seen in the clinical endpoints of tumor regression and patient survival. However, scant clinical evidence supports the use of melatonin in bladder cancer treatment. Our study has found that melatonin treatment suppresses the bladder cancer cell migratory ability by inhibiting the epithelial-mesenchymal transition (EMT) process, which appears to be linked to melatonin-induced decreases in bladder cancer cell autophagy. Finally, an evaluation of in vivo melatonin-induced antitumor effects in an orthotopic animal model of bladder cancer indicated that melatonin treatment slightly prolonged the survival of tumor-bearing mice. Our study offers novel insights into the use of melatonin in bladder cancer treatment. [ABSTRACT FROM AUTHOR]

Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The various manifestations of anxiety, its complex pathophysiological background and the side effects of available treatments underlie the quest for constantly seeking therapies for these conditions. Melatonin, an indolamine produced in the pineal gland and released into the blood on a nightly basis, has been demonstrated to exert anxiolytic action in animal experiments and different clinical conditions. This hormone influences a number of physiological actions either via specific melatonin receptors or by receptor-independent pleiotropic effects. The underlying pathomechanism of melatonin's benefit in anxiety may reside in its sympatholytic action, interaction with the renin–angiotensin and glucocorticoid systems, modulation of interneuronal signaling and its extraordinary antioxidant and radical scavenging nature. Of importance, the concentration of this indolamine is significantly higher in cerebrospinal fluid than in the blood. Thus, ensuring sufficient melatonin production by reducing light pollution, which suppresses melatonin levels, may represent an endogenous neuroprotective and anxiolytic treatment. Since melatonin is freely available, economically undemanding and has limited side effects, it may be considered an additional or alternative treatment for various conditions associated with anxiety. [ABSTRACT FROM AUTHOR]

One of the most common neurological disorders involving oxidative stress is stroke. During a stroke, the balance of redox potential in the cell is disturbed, and, consequently, protein oxidation or other intracellular damage occurs, ultimately leading to apoptosis. The pineal gland hormone, melatonin, is one of the non-enzymatic antioxidants. It not only modulates the perianal rhythm but also has anti-inflammatory properties and protects against stress-induced changes. The focus of this research was to evaluate the concentration of the carbonyl groups and melatonin metabolite in time in patients with acute ischemic stroke that were treated with intravenous thrombolysis. This included a comparison of the functional status of patients assessed according to neurological scales with the control sample comprising healthy people. The studies showed that the serum concentrations of carbonyl groups, which were elevated in patients with ischemic stroke (AIS) in comparison to the control samples, had an impact on the patients' outcome. A urine concentration of the melatonin metabolite, which was lower in patients than controls, was related to functional status after 24 h from cerebral thrombolysis. It shows that determination of carbonyl groups at different time intervals may be an important potential marker of protein damage in patients with AIS treated with cerebral thrombolysis, and that impaired melatonin metabolism induces a low antioxidant protection. Thus, due to the neuroprotective effects of melatonin, attention should also be paid to the design and conduct of clinical trials and hormone supplementation in AIS patients to understand the interactions between exogenous melatonin and its endogenous rhythm, as well as how these relationships may affect patient outcomes. [ABSTRACT FROM AUTHOR]

The circadian rhythm of melatonin secretion in the pineal gland is highly conserved in vertebrates. Melatonin levels are always elevated at night. Acetylserotonin O-methyltransferase (ASMT) is the last enzyme in the regulation of melatonin biosynthesis (N-acetyl-5-hydroxytryptamine-melatonin). S-adenosylmethionine (SAM) is an important methyl donor in mammals and can be used as a substrate for the synthesis of melatonin. Methionine adenosyltransferase (MAT) catalyzes the synthesis of SAM from methionine and ATP and has a circadian rhythm. CircRNA is an emerging type of endogenous noncoding RNA with a closed loop. Whether circRNAs in the pineal gland can participate in the regulation of melatonin synthesis by binding miRNAs to target mat2a as part of the circadian rhythm is still unclear. In this study, we predicted the targeting relationship of differentially expressed circRNAs, miRNAs and mRNAs based on the results of rat pineal RNA sequencing. Mat2a siRNA transfection confirmed that mat2a is involved in the synthesis of melatonin. Circ-ERC2 and miR-125a-5p were screened out by software prediction, dual-luciferase reporter experiments, cell transfection, etc. Finally, we constructed a rat superior cervical ganglionectomy model (SCGx), and the results showed that circ-ERC2 could participate in the synthesis of melatonin through the miR-125a-5p/MAT2A axis. The results of the study revealed that circ-ERC2 can act as a molecular sponge of miR-125a-5p to regulate the synthesis of melatonin in the pineal gland by targeting mat2a. This experiment provides a basis for research on the circadian rhythm of noncoding RNA on pineal melatonin secretion. [ABSTRACT FROM AUTHOR]

Background: Asymmetric pupil reactivity or size can be early clinical indicators of midbrain compression due to supratentorial ischemic stroke or primary intraparenchymal hemorrhage (IPH). Radiographic midline shift is associated with worse functional outcomes and life-saving interventions. Better understanding of quantitative pupil characteristics would be a non–invasive, safe, and cost-effective way to improve identification of life-threatening mass effect and resource utilization of emergent radiographic imaging. We aimed to better characterize the association between midline shift at various anatomic levels and quantitative pupil characteristics. Methods: We conducted a multicenter retrospective study of brain CT images within 75 min of a quantitative pupil observation from patients admitted to Neuro-ICUs between 2016 and 2020 with large (>1/3 of the middle cerebral artery territory) acute supratentorial ischemic stroke or primary IPH > 30 mm³. For each image, we measured midline shift at the septum pellucidum (MLS-SP), pineal gland shift (PGS), the ratio of the ipsilateral to contralateral midbrain width (IMW/CMW), and other exploratory markers of radiographic shift/compression. Pupil reactivity was measured using an automated infrared pupillometer (NeurOptics®, Inc.), specifically the proprietary algorithm for Neurological Pupil Index® (NPi). We used rank-normalization and linear mixed-effects models, stratified by diagnosis and hemorrhagic conversion, to test associations of radiographic markers of shift and asymmetric pupil reactivity (Diff NPi), adjusting for age, lesion volume, Glasgow Coma Scale, and osmotic medications. Results: Of 53 patients with 74 CT images, 26 (49.1%) were female, and median age was 67 years. MLS-SP and PGS were greater in patients with IPH, compared to patients with ischemic stroke (6.2 v. 4.0 mm, 5.6 v. 3.4 mm, respectively). We found no significant associations between pupil reactivity and the radiographic markers of shift when adjusting for confounders. However, we found potentially relevant relationships between MLS-SP and Diff NPi in our IPH cohort (β = 0.11, SE 0.04, P = 0.01), and PGS and Diff NPi in the ischemic stroke cohort (β = 0.16, SE 0.09, P = 0.07). Conclusion: We found the relationship between midline shift and asymmetric pupil reactivity may differ between IPH and ischemic stroke. Our study may serve as necessary preliminary data to guide further prospective investigation into how clinical manifestations of radiographic midline shift differ by diagnosis and proximity to the midbrain. [ABSTRACT FROM AUTHOR]

Physiological intracranial calcifications have an increasing prevalence with the age and can be found in both children and in adults. These calcifications are basically asymptomatic and their presence can only be noticed through neuro-imaging. The aim of the paper was to evaluate physiological intracranial calcifications in children using computed tomography, in our conditions. The study was designed as a retrospective, observational, nonrandomized clinical study. It was conducted at the Department of Radiology, Clinical Center Kragujevac, Serbia. The study included all the patients scanned by CT from 1st October, 2008. to 30th September, 2018.. The criteria for the inclusion were: the patients aged up to 18 years who underwent a non-contrast computed tomography in the observed period, with diagnosed intracranial calcifications that do not have pathological etiology. Our study included 420 patients. Out of them, 213 (50.7%) were boys and 207 (49.3%) were girls. The mean age was 12.47. We divided the patients into two age categories: the first one included the patients aged 1 to 10 years and the other one included the patients aged 11 to 18 years. Our study has demonstrated that physiological intracranial calcifications are the most frequent in habenula (28.1%), followed by the pineal gland (22.6%) and choroid plexus (18.8%). There is a small number of studies with the subject of physiological intracranial calcification distribution, especially in children. It is important to know in which locations we can expect physiological intracranial calcifications, as well as the age in which they become detectable by imaging, in order not to mix them with hemorrhages, pathological tumor or metabolic mineralization. [ABSTRACT FROM AUTHOR]

Melatonin is an endogenous chronobiological regulator secreted mainly from the pineal gland, which has been used as a dietary supplement in the treatment of sleep problems, including insomnia, parasomnia, and circadian rhythm sleep disorders. However, the short half-life and rapid metabolism of melatonin limit its suitability as a drug. There are many melatonergic drugs used in the treatment of sleep disorders and several drugs are under investigation for approval. Ramelteon was the first melatonergic agonist approved as hypnotic agent by U.S. Food and Drug Administration for the treatment of insomnia. It exhibits higher selective affinity for melatonin 1a (MT1) receptor than melatonin 1b (MT2) receptor. This selectivity suggests that it targets sleep onset with no significant adverse effect or dependency. Agomelatin, naphtahalenic compound, act as a potent MT1/MT2 melatonergic receptor agonist and serotonergic receptor antagonist was approved for treatment of depression in 2009. This dual action drug is the first melatonergic agent used in depression. Another melatonergic agonist, tasimelteon has high affinity for the MT1/MT2 receptors in humans. It was approved for the treatment of non-24 hours sleep-wake rhythm disorder. The newly developed melatonin and melatonergic drugs have the potential to be used extensively in various clinical situations and substitute the old benzodiazepine and its derivatives in the treatment of insomnia. However, the efficacy and safety of newly developed melatonergic drugs should be elucidated through long-term clinical trials. [ABSTRACT FROM AUTHOR]

For many years, it was generally accepted that melatonin and somatostatin have intracerebral sources of synthesis. Melatonin is produced in the pineal gland and somatostatin in the hypothalamus. However, there are very informative data regarding the extracerebral sources of melatonin and somatostatin synthesis in numerous literary sources published over the past 60 years. At the same time, the biological purpose of extracerebral somatostatin and melatonin has been insufficiently studied. This article presents the readers with an analysis of modern literature and the results of own researches on the biological role of melatonin and somatostatin produced in the pancreas and intestinal tract. Under experimental conditions on arginine-induced acute pancreatitis model in rats, structural and hormonal changes were studied in the pancreas, mucosa of the small and large intestines in regional pathological process using morphological, morphometric, immunomorphological and enzyme immunoassay methods. According to the morphological and morphometric analysis results, gross dystrophic changes in the pancreas and intestinal mucosa were observed at relatively early stages of the pathological process – in 2 and 24 hours after the arginine administration. Immunomorphological studies established that the content of melatonin-positive secretory cells noticeably decreased, especially in the areas of mucosal damage in this very period of the pathological process in pancreas, in the mucous membrane of the small and large intestines. At the same time, the content of somatotropin in blood serum and pancreas markedly increased during the indicated period of the experiment. Severe dystrophic processes on small intestinal mucosa, which are particularly expressed by inhibition of local melatonin-secreting cell function, apparently exclude the inhibitory effect of melatonin on somatostatin synthesis process in pancreas. It is not excluded that there is a directed activation of pancreatic delta cells responsible for the somatostatin synthesis at relatively early stages of “arginine pancreatitis”. Based on our own researches in context with available very informative literature data, we can conclude that extrapineal melatonin and extrahypothalamic somatostatin should be given an important role in the integrative activity of organ-digestive system – the pancreas and small intestine. [ABSTRACT FROM AUTHOR]

Infertility is a major global health issue and male factors account for half of all infertility cases. One of the causes of male infertility is the loss of spermatogonial stem cells, which may occur because of chemotherapy, radiotherapy or genetic defects. In numerous animal species, the evidence suggests the pineal gland and melatonin secretion in their reproductive activities are involved. Recently, considerable attention has pointed to the usage of melatonin in the treatment of diseases. Melatonin is associated with the regulation of circadian and seasonal rhythmic functions, immune system functions, retinal physiology, spermatogenesis and inhibition of tumour growth in different species. Several studies demonstrated that melatonin acts as an anti‐apoptotic, anti‐inflammatory, anticancer and antioxidant agent. Melatonin can also protect testicles and spermatogonia against oxidative damage, chemotherapy drugs, environmental radiation, toxic substances, hyperthermia, ischemia/reperfusion, diabetes‐induced testicular damage, metal‐induced testicular toxicity, improve sperm quality and it affects the testosterone secretion pathway by affecting Leydig cells. Therefore, the objective of this study is to investigate the biological effects of melatonin as a natural antioxidant on testicles and their disorders. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 virus gains entry to cells by binding to angiotensin-converting enzyme 2 (ACE2). Since circumventricular organs and parts of the hypothalamus lack a blood–brain barrier, and immunohistochemical studies demonstrate that ACE2 is highly expressed in circumventricular organs which are intimately connected to the hypothalamus, and the hypothalamus itself, these might be easy entry points for SARS-CoV-2 into the brain via the circulation. High ACE2 protein expression is found in the subfornical organ, area postrema, and the paraventricular nucleus of the hypothalamus (PVH). The subfornical organ and PVH are parts of a circuit to regulate osmolarity in the blood, through the secretion of anti-diuretic hormone into the posterior pituitary. The PVH is also the stress response centre in the brain. It controls not only pre-ganglionic sympathetic neurons, but is also a source of corticotropin-releasing hormone, that induces the secretion of adrenocorticotropic hormone from the anterior pituitary. It is proposed that the function of ACE2 in the circumventricular organs and the PVH could be diminished by binding with SARS-CoV-2, thus leading to a reduction in the ACE2/Ang (1–7)/Mas receptor (MasR) signalling axis, that modulates ACE/Ang II/AT1R signalling. This could result in increased presympathetic activity/neuroendocrine secretion from the PVH, and effects on the hypothalamic–pituitary–adrenal axis activity. Besides the bloodstream, the hypothalamus might also be affected by SARS-CoV-2 via transneuronal spread along the olfactory/limbic pathways. Exploring potential therapeutic pathways to prevent or attenuate neurological symptoms of COVID-19, including drugs which modulate ACE signalling, remains an important area of unmet medical need. [ABSTRACT FROM AUTHOR]

Surface‐dwelling C. catla were exposed to different photoperiods (8L:16D, 12L:12D, 12D:12L and 16L:8D) and the mRNA level profile of enzymes involved in melatonin synthesis was evaluated in the pineal gland and retina. Furthermore, a comparative analysis of the serum melatonin profile with the mRNA level was also performed. The results indicated diurnal variations in the transcripts of tph1, aanat and hiomt in the pineal organ and retina, and these variations change with the change in lighting regime. The serum melatonin profile showed rhythmicity in the natural photoperiod, but the serum melatonin level increased proportionally with increasing daylength. In short photoperiods, the peak value (though lower than in long photoperiods) of melatonin maintains a longer duration in serum. Moreover, the comparative analysis revealed a similar profile of mRNA of pineal aanat1 and aanat2 with serum melatonin under the same lighting conditions. This indicates that serum melatonin is produced by the pineal gland. Our results specify the importance of day length and the timing of onset or offset of the dark for maintaining the oscillating levels of serum melatonin and mRNA levels of melatonin biosynthesizing enzyme genes in the pineal organ and retina as well. The findings in this study highlight the distinctive pattern of mRNA levels in the pineal organ and retina under different photoperiods. The pineal melatonin biosynthesizing enzyme genes showed a similar pattern with serum melatonin levels while the retinal genes changed dramatically with photoperiod. We also revealed a light‐dependent transcriptional regulation of pineal aanat genes in C. catla. Moreover, our results suggest that ALAN and skyglow can influence the levels of serum melatonin and its biosynthesis, resulting in desynchronization of the entire biological clock as well as the overall physiology of the animal. [ABSTRACT FROM AUTHOR]

The circadian timing system is synchronized by the environmental photic and non-photic signals. Light is the major cue that entrains the master circadian oscillator located in suprachiasmatic nucleus (SCN). With aging condition ocular light impairs because of the age-related deficiencies in the eye as a result the clock becomes less sensitive to light. In such case non-photic cues may play a major role in synchronizing the clock. Earlier studies have linked altered meal timings to induce many physiological changes including serotonin in different brain regions such as hypothalamus, brain stem and striatum. Much is not known about the effect of timed food restriction as a non-photic stimulus on serotonergic system in SCN under aging condition. We report here the synchronizing effects of time-restricted feeding (TRF) as a non-photic stimulus on serotonin and its related metabolites in the SCN and pineal gland of male Wistar rats upon aging. Under food restriction daily rhythmicity of serotonin 5-HT and 5-HTOH was abolished whereas NAS, 5-MIAA and NAT showed a significant decrease in their daily pulses upon food restriction in 3 months (m) old rats. Under forced day time feeding schedule the mean 24 h levels of serotonin have significantly decreased in 12 and 24 m old animals in SCN and pineal gland. Most of the serotonin metabolites in the SCN and pineal gland of 12 and 24 m old ad libitum fed group rats have shown rhythmicity. 5-HT, NAS, MEL and NAT have shown daily rhythm in the SCN of 12 and 24 m old rats whereas 5-MIAA and 5-MTOH did not show daily rhythm in both the age groups. The mean 24 h levels of 5-HTP, 5-HIAA, 5-MIAA, 5-MTOH, MEL and NAT were increased in the pineal gland of 12 and 24 months old rats. This work help demonstrate the role of TRF in synchronising age induced desynchronization in serotonin metabolome. [ABSTRACT FROM AUTHOR]

Lung cancer is the second most common cancer and the most lethal cancer worldwide. Melatonin, an indoleamine produced in the pineal gland, shows anticancer effects on a variety of cancers, especially lung cancer. Herein, we clarify the pathophysiology of lung cancer, the association of circadian rhythm with lung, and the relationship between shift work and the incidence of lung cancer. Special focus is placed on the role of melatonin receptors in lung cancer, the relationship between inflammation and lung cancer, control of cell proliferation, apoptosis, autophagy, and immunomodulation in lung cancer by melatonin. A review of the drug synergy of melatonin with other anticancer drugs suggests its usefulness in combination therapy. In summary, the information compiled may serve as a comprehensive reference for the various mechanisms of action of melatonin against lung cancer, as a guide for the design of future experimental research and for advancing melatonin as a therapeutic agent for lung cancer. [ABSTRACT FROM AUTHOR]

As per vascular engineering, the horizontal ventricle choroid plexus can be parted into three sections: rostral, caudal and center. Under binocular magnifying instrument, the two tight groups that shaped from the choroid plexuses of the sidelong ventricles got through the interventricular foramen, framing the choroid plexus of the third ventricle; each band looked as down collapsing liner tufts arriving at the level of the pineal body. The choroid plexuses of the third and fourth ventricles were comprised of an immense number of foliate-like cycles joined by a stem to a more basal center of the stromal tissue. Essential foliate may create optional leaf-like rises. The stromal tissue choroid plexus became bigger and exceptionally vascular in its construction covered with a solitary layer of ciliated cuboidal epithelium. The veins were isolated from the epithelium by a somewhat high measure of connective tissue. The sidelong ventricle's blood channels were long, expansive, marginally tangled, and reasonably equal. [ABSTRACT FROM AUTHOR]

A photoperiod is the time duration when animals are exposed to light in an entire day. An exposure of 16 hours or more is considered a long-day photoperiod and 8 hours of light is a short-day photoperiod. Exposure to light prevents the secretion of melatonin from the pineal gland. Melatonin can influence the release of several hormones, including prolactin, cortisol, kisspeptin, GnRH and others. Eventually, it can also affect the reproductive performance of the animal. Though cattle are not a seasonal breeder, photoperiod has an indirect role in the onset of puberty, pregnancy and parturition. It can also promote the growth rate of the heifers and enhance their reproductive capabilities, which are very much desired by the producers. Therefore, photoperiod can be used as an effective and non-invasive tool in the reproductive management of cattle. [ABSTRACT FROM AUTHOR]

Background: Based on the effect of seasonal changes on human visceral function, this study investigated the impact of seasonal photoperiod of the pineal body on hypothalamic-pituitary-adrenal axis-hippocampal-receptor in rats, aiming to reveal the mechanism by which pineal gland melatonin regulates the seasonal secretion of hippocampal neurotransmitters. Methods: Vernal equinox, summer solstice, autumn equinox, and winter solstice were selected as four experimental time points, and rats were randomly divided into normal control group, sham operation group, and pinealectomized group. The seasonal changes in corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone, hypothalamic melatonin receptor (MTR), and hippocampal corticosterone receptor (CORTR) were examined by enzyme-linked immunosorbent assay. Results: Comparing the same group between different seasons, we showed that in the normal control group, CRH, ACTH, corticosterone, and MTR were higher, while CORTR was lower in autumn and winter than in spring (all P

Abstract Background The causes of an early onset of puberty are still not clearly defined and may vary from subject to subject. In girls, even if 90% of early puberty is idiopathic, magnetic resonance imaging (MRI) of the brain is performed to exclude secondary causes of precocious puberty, in particular pathological lesions as hypothalamic tumours (hamartoma). In some cases, other intracranial lesions are considered as incidental findings. Aim of the study is evaluating the prevalence of abnormal intracranial lesions detected by brain magnetic resonance imaging MRI with particular focus on the prevalence of pineal gland cysts in the diagnostic work-up of girls with central precocious puberty (CPP) as onset before 8 years and central early puberty (CEP) as onset before 10 years. Material and methods MRI data of girls referred from January 2010 to December 2015 to the Pediatric Endocrinology Unit of University of Pavia for early onset of breast development were collected. Results We collected 123 MRI data of girls referred to the Pediatric Endocrinology Unit of University of Pavia for early onset of breast development in the study period. Out of them, 25 (20.3%) had cerebral abnormalities and 15 (12.2%) had pineal gland cysts. No significant differences were noted in auxological, ultrasound and hormonal parameters at diagnosis among girls with or without pineal cysts. Patients have been observed for at least three years after the discontinuation of therapy. None of our patients had an unfavorable evolution. Conclusions Although pineal cysts seem to be not involved in the onset of puberty, the relevance of the finding remains controversial. Our study wants to provide further insight into the incidence of pineal cysts in pubertal advances. Of note, pineal cysts are often asymptomatic and do not evolve over time.

The pineal gland is a small and poorly studied neuroendocrine gland located in the epithalamus. There is growing interest in the pineal gland due to its role in regulating human biological rhythms, which is associated with melatonin production, and its close neuroendocrine link between the brain's hormonal and neurally mediated activity. The paper examines the anatomical and physiological features of the pineal gland, its structural variations, and the role of the melatonin it produces in the pathogenesis of several mental and neurological disorders.

Microglial cells are one of the interstitial elements of the pineal gland (PG). We recently reported the pattern of microglia colonization and activation, and microglia-Pax6+ cell interactions during normal pineal ontogeny. Here, we describe the dynamics of microglia-Pax6+ cell associations and interactions after surgical or pharmacological manipulation. In adult rats, the superior cervical ganglia (SCG) were exposed, and either bilaterally excised (SCGx) or decentralized (SCGd). In the SCGx PGs, the density of Iba1+ microglia increased after surgery and returned to sham baseline levels 13 days later. Pineal microglia also responded to SCGd, a more subtle denervation. The number of clustered Iba1+ /PCNA+ /ED1+ microglia was higher 4 days after both surgeries compared to the sham-operated group. However, the number of Pax6+ /PCNA- cells and the percentage of Pax6+ cells contacted by and/or phagocytosed by microglia increased significantly only after SCGx. Separate groups of rats were treated with either bacterial lipopolysaccharides (LPS) or doxycycline (DOX) to activate or inhibit pineal microglia, respectively. Peripheral LPS administration caused an increase in the number of clustered Iba1+ /PCNA+ /ED1+ microglial cells, and in the percentage of Pax6+ cells associated with and/or engulfed by microglia. In the LPS-treated PGs, we also noted an increase in the number of PCNA+ cells that were Iba1- within the microglial cell clusters. The density of Pax6+ cells did not change after LPS treatment. DOX administration did not influence the parameters analyzed. These data suggest that pineal microglia are highly receptive cells capable of rapidly responding in a differential manner to surgical and pharmacological stimuli.