Much attention has been recently drawn to studying melatonin – a hormone whose synthesis was first found in the epiphysis (pineal gland). This interest can be due to discovering the role of melatonin in numerous physiological processes. It was the discovery of melatonin synthesis in endocrine organs (pineal gland), neural structures (Purkinje cells in the cerebellum, retinal photoreceptors), and immunocompetent cells (T lymphocytes, NK cells, mast cells) that triggered the evolution of new approaches to the unifield signal regulation of homeostasis, which, at the turn of the 21st century, lead to the creation of a new integral biomedical discipline — neuroimmunoendocrinology. While numerous hormones have been verified over the last decade outside the “classical” locations of their formation, melatonin occupies an exclusive position with regard to the diversity of locations where it is synthesized and secreted. This review provides an overview and discussion of the major data regarding the role of melatonin in various physiological and pathological processes, which affords grounds for considering melatonin as the “cornerstone” on which neuroimmunoendocrinology has been built as an integral concept of homeostasis regulation.

Embryogenesis is a complex multi-stage process regulated by various signaling molecules including pineal and extrapineal melatonin (MT). Extrapineal MT is found in the placenta and ovaries, where it carries out local hormonal regulation. MT is necessary for normal development of oocytes, fertilization and subsequent development of human, animal and avian embryos. This review discusses the role of MT as a regulator of preimplantation development of the embryo and its implantation into endometrial tissue, followed by histo-, morpho- and organogenesis. MT possesses pronounced antioxidant properties and helps to protect the embryo from oxidative stress by regulating the expression of the NFE2L2, SOD1, and GPX1 genes. MT activates the expression of the ErbB1, ErbB4, GJA1, POU5F1, and Nanog genes which are necessary for embryo implantation and blastocyst growth. MT induces the expression of vascular endothelial growth factor (VEGF) and its type 1 receptor (VEGF-R1) in the ovaries, activating angiogenesis. Given the increased difficulties in successful fertilization and embryogenesis with age, it is of note that MT slows down ovarian aging by increasing the transcription of sirtuins. MT administration to patients suffering from infertility demonstrates an increase in the effectiveness of in vitro fertilization. Thus, MT may be viewed as a key factor in embryogenesis regulation, including having utility in the management of infertility.

There is a growing awareness that pregnancy can set the foundations for an array of diverse medical conditions in the offspring, including obesity. A wide assortment of factors, including genetic, epigenetic, lifestyle, and diet can influence foetal outcomes. This article reviews the role of melatonin in the prenatal modulation of offspring obesity. A growing number of studies show that many prenatal risk factors for poor foetal metabolic outcomes, including gestational diabetes and night-shift work, are associated with a decrease in pineal gland-derived melatonin and associated alterations in the circadian rhythm. An important aspect of circadian melatonin’s effects is mediated via the circadian gene, BMAL1, including in the regulation of mitochondrial metabolism and the mitochondrial melatoninergic pathway. Alterations in the regulation of mitochondrial metabolic shifts between glycolysis and oxidative phosphorylation in immune and glia cells seem crucial to a host of human medical conditions, including in the development of obesity and the association of obesity with the risk of other medical conditions. The gut microbiome is another important hub in the pathoetiology and pathophysiology of many medical conditions, with negative consequences mediated by a decrease in the short-chain fatty acid, butyrate. The effects of butyrate are partly mediated via an increase in the melatoninergic pathway, indicating interactions of the gut microbiome with melatonin. Some of the effects of melatonin seem mediated via the alpha 7 nicotinic receptor, whilst both melatonin and butyrate may regulate obesity through the opioidergic system. Oxytocin, a recently recognized inhibitor of obesity, may also be acting via the opioidergic system. The early developmental regulation of these processes and factors by melatonin are crucial to the development of obesity and many diverse comorbidities.

The review summarizes the results of experimental and clinical studies aimed at elucidating the causes and pathophysiological mechanisms of the development of endocrine pathology in children. The modern data on the role of epigenetic influences in the early ontogenesis of unfavorable factors that violate the patterns of the formation of regulatory mechanisms during periods of critical development of fetal organs and systems and contribute to the delayed development of pathological conditions are considered. The mechanisms of the participation of melatonin in the regulation of metabolic processes and the key role of maternal melatonin in the formation of the circadian system of regulation in the fetus and in the protection of the genetic program of its morphofunctional development during pregnancy complications are presented. Melatonin, by controlling DNA methylation and histone modification, prevents changes in gene expression that are directly related to the programming of endocrine pathology in offspring. Deficiency and absence of the circadian rhythm of maternal melatonin underlies violations of the genetic program for the development of hormonal and metabolic regulatory mechanisms of the functional systems of the child, which determines the programming and implementation of endocrine pathology in early ontogenesis, contributing to its development in later life. The significance of this factor in the pathophysiological mechanisms of endocrine disorders determines a new approach to risk assessment and timely prevention of offspring diseases even at the stage of family planning.

In the Russian Federation, the proportion of children among all cases of new coronavirus infection is up to 8.6%. Mild forms are registered in 80% of cases, severe – 0.2%, as a rule, in children of the first year of life. The majority of deaths were recorded in children with an unfavorable background: 75% of those who died had one concomitant pathology, 45% – two or more. The problem of severe course and fatal outcomes from COVID-19 in children with comorbid pathology, for example, with various forms of leukemia, remains relevant. Severe infectious complications of bacterial nature are observed in 70–80% of sick children, viral and fungal genesis, respectively, in 4–12% and 18–20%. Myeloblastic leukemia is one of the factors that predispose to a severe course of COVID-19 and an unfavorable outcome. The article presents a clinical observation of the course of a critical form of a new coronavirus infection in a young child with acute myeloblastic leukemia. The layering of COVID-19 contributed to a sharp deterioration of the underlying disease. Despite the highly organized treatment process with the use of modern technologies, the child had a rapid deterioration of the condition with a fatal outcome. Key words: COVID-19, children, acute myeloblastic leukemia, pancytopenia, fatal outcome

: Aging is a complex biological process, a major aspect of which is the accumulation of somatic changes throughout life. Cellular senescence is a condition in which cells undergo an irreversible cell cycle arrest in response to various cellular stresses. Once the cells begin to senesce, they become more resistant to any mutagens, including oncogenic factors. Inflammaging (inflammatory aging) is an age-related, chronic, and systemic inflammatory condition realized by cells with the Senescence-Associated Secretory Phenotype (SASP). These recently recognized senescent phenotypes associated with aging have been reported to promote better wound healing, embryonic development, as well as stimulation and extension of the tumor process. It is assumed that cellular senescence contributes to the age-related decline of reproductive function due to the association of senescent cells with aging and age-related diseases. Thus, SASPs have both positive and negative effects, depending on the biological context. SASP cell accumulation in tissues contributes to an age-related functional decline of the tissue and organ state. In this review, the term “cellular senescence” is used to refer to the processes of cells irreversible growth inhibition during their viable state, while the term “aging” is used to indicate the deterioration of tissues due to loss of function. Late reproductive age is associated with infertility and possible complications of the onset and maintenance of pregnancy. Senescent cells express pro-inflammatory cytokines, growth factors, and matrix metalloproteinases and some other molecules collectively called the Senescence-Associated Secretory Phenotype (SASP).