Nervous Regulation Research Articles

A review of dolutegravir-associated weight gain and secondary metabolic comorbidities.

Dolutegravir is an integrase inhibitor and is recommended by the World Health Organization as the preferred first-line and second-line human immunodeficiency virus treatment in all populations. Excessive weight gain associated with dolutegravir-based regimens is an emerging issue; however, the long-term metabolic consequences of this effect have not been fully understood. Growing evidence shows that this leads to a higher incidence of hyperglycemia, hypertension, and metabolic syndrome, along with elevated cardiovascular risk. Dolutegravir-based regimens, also associated with greater adipocyte differentiation and greater expression of markers associated with lipid storage, continue to be a problem among patients living with human immunodeficiency virus. The mechanisms by which certain antiretroviral therapy agents differentially contribute to weight gain remain unknown. Some clinical investigators speculate that dolutegravir could interfere with central nervous system appetite regulation (melanocortin-4 receptor) and insulin signaling, or may have better penetration of adipose tissue where they could exert a direct impact on adipose tissue adipogenesis, fibrosis, and insulin resistance. This review summarizes our current understanding of weight gain and fat changes associated with dolutegravir and its possible secondary metabolic comorbidities.

Profiling Novel Quinuclidine-Based Derivatives as Potential Anticholinesterase Drugs: Enzyme Inhibition and Effects on Cell Viability.

The cholinergic system, relying on the neurotransmitter acetylcholine (ACh), plays a significant role in muscle contraction, cognition, and autonomic nervous system regulation. The enzymes acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, responsible for hydrolyzing ACh, can fine-tune the cholinergic system's activity and are, therefore, excellent pharmacological targets to address a range of medical conditions. We designed, synthesized, and profiled 14 N-alkyl quaternary quinuclidines as inhibitors of human AChE and BChE and analyzed their impact on cell viability to assess their safety in the context of application as potential therapeutics. Our results showed that all of the 14 tested quinuclidines inhibited both AChE and BChE in the micromolar range (Ki = 0.26 - 156.2 μM). The highest inhibition potency was observed for two bisquaternary derivatives, 7 (1,1'-(decano)bis(3-hydroxyquinuclidinium bromide)) and 14 (1,1'-(decano)bis(3-hydroxyiminoquinuclidinium bromide)). The cytotoxic effect within 7-200 μM was observed only for monoquaternary quinuclidine derivatives, especially those with the C12-C16 alkyl chain. Further analysis revealed a time-independent mechanism of action, significant LDH release, and a decrease in the cells' mitochondrial membrane potential. Taking all results into consideration, we can confirm that a quinuclidine core presents a good scaffold for cholinesterase binding and that two bisquaternary quinuclidine derivatives could be considered as candidates worth further investigations as drugs acting in the cholinergic system. On the other hand, specific cell-related effects probably triggered by the free long alkyl chain in monoquaternary quinuclidine derivatives should not be neglected in future N-alkyl quaternary quinuclidine derivative structure refinements. Such an effect and their potential to interact with other specific targets, as indicated by a pharmacophore model, open up a new perspective for future investigations of these compounds' scaffold in the treatment of specific conditions and diseases other than cholinergic system-linked disorders.

The gut microbiome - an essential role for human health

The complex and vast ecosystem of microorganisms within the gut, known as the gut microbiome, plays an important role in regulating numerous biological systematics. From immune system function and metabolism to brain health and enteric nervous system regulation, dysbiosis or changes in its composition can have significant impacts on human wellbeing such as autoimmune diseases, metabolic disorders, neurological and psychiatric disorders, and enteric neuropathies. Fortunately, research has uncovered the potential for targeting and manipulating the gut microbiome as a strategy in managing a wide variety of human ailments. By focusing on promoting a healthy balance within the guts microbial community, experts believe that theoretically curative treatments could arise related to the reduction/prevention of many diverse conditions which affect overall health. Through advances in understanding this crucial mechanism, we may be able to develop more effective therapies to promote optimal human health. As genetic sequencing technology continues expanding our knowledge in the field, future breakthroughs await those who patiently continue studying the fascinating world of the gut microbiome.

Application of artificial hibernation technology in acute brain injury.

Controlling intracranial pressure, nerve cell regeneration, and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury. There is currently a lack of effective treatment methods. Hibernation has the characteristics of low temperature, low metabolism, and hibernation rhythm, as well as protective effects on the nervous, cardiovascular, and motor systems. Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body's metabolism, lowering the body's core temperature, and allowing the body to enter a state similar to hibernation. This review introduces artificial hibernation technology, including mild hypothermia treatment technology, central nervous system regulation technology, and artificial hibernation-inducer technology. Upon summarizing the relevant research on artificial hibernation technology in acute brain injury, the research results show that artificial hibernation technology has neuroprotective, anti-inflammatory, and oxidative stress-resistance effects, indicating that it has therapeutic significance in acute brain injury. Furthermore, artificial hibernation technology can alleviate the damage of ischemic stroke, traumatic brain injury, cerebral hemorrhage, cerebral infarction, and other diseases, providing new strategies for treating acute brain injury. However, artificial hibernation technology is currently in its infancy and has some complications, such as electrolyte imbalance and coagulation disorders, which limit its use. Further research is needed for its clinical application.

COMPARATIVE CHARACTERISTICS OF AUTONOMIC IMBALANCE DIAGNOSTIC METHODS IN SCHOOL-AGE CHILDREN

Introduction. An imbalance in the autonomic nervous system regulation, known as dysautonomia, is one of the most common clinical syndromes that accompany several diseases. The balance between sympathetic and parasympathetic influences on the body can rapidly change during dynamic processes, especially in cases of infectious and acute diseases, where autonomic regulation plays an active role in shaping the immune response. In children with respiratory diseases, the influence of the vagus nerve (n.vagus) on the frequency and depth of breathing is also important but remains relatively understudied. Assessment of vegetative balance in pediatrics is carried out using various methods depending on the child's age and condition, with commonly used approaches including questionnaires, calculation of the Kerdo autonomic index, and orthostatic testing.
 The aim. To compare the diagnostic capabilities of different methods for assessment of the autonomic nervous system state in school-age children on the model of acute bronchitis.
 Materials and methods. The paper presents data from a study that assessed the state of the autonomic nervous system in 52 school-age children (12-16 years old) divided into two groups: 30 children with acute bronchitis in the convalescent period and 22 clinically healthy individuals. Three different methods were used: the A.M. Wayne scale, the Kerdo index, and the orthostatic test.
 Results. The survey based on Wayne's questionnaire did not reveal a significant difference between the groups of healthy children and those affected by bronchitis. Dynamic tests proved to be more suitable for assessing acute pathology, such as Kerdo's autonomic index and the orthostatic test. The autonomic Kerdo index in children with bronchitis was significantly higher (14.2±2.38 points) than in healthy children (6.4±3.18 points, p<0.05). In children with acute bronchitis, dysautonomia with a predominance of sympathicotonia was recorded, which may be attributed to insufficient vagal innervation and a decrease in parasympathetic influence on the formation of an adequate immune response to the inflammatory process in the respiratory tract.
 Conclusions. Determining the autonomic Kerdo index and conducting the orthostatic test is suitable for diagnosing dysautonomia in children with acute respiratory pathology. These tests are dynamic, functionally based, and easy to perform and evaluate.

Anthracycline's Effects on Heart Rate Variability in Children with Acute Lymphoblastic Leukemia: Early Toxicity Signs-Pilot Study.

Anthracycline treatments are known to cause cardiotoxic long-term side effects in cancer survivors. Recently, a decrease in heart rate variability (HRV) has been identified in these patients, signaling autonomic dysfunction and altered cardiac fitness. This study aimed at evaluating changes in HRV in children treated with anthracyclines. A total of 35 pediatric patients with acute lymphoblastic leukemia were evaluated by means of a 24 h Holter ECG, at baseline and after reaching half the total cumulative dose of doxorubicin equivalent (120 mg/m2). Parameters of HRV were assessed, as well as any arrhythmic episodes, bradycardia and tachycardia percentages. The results showed a significant decrease in both time-domain and frequency-domain HRV parameters, following anthracycline treatment. The low-frequency (LF) to high-frequency (HF) parameters' ratio also displayed a significant difference (p = 0.035), suggestive of early cardiac autonomic dysfunction. Of note, none of the patients presented symptoms of heart disease or elevated troponins, and only two patients presented echocardiographic signs of diastolic dysfunction. The present study showed that cardiac autonomic nervous system regulation is compromised in children treated with anthracyclines even before reaching the total cumulative dose. Therefore, HRV parameters could be the first indicators of subclinical cardiac toxicity, making Holter ECG monitoring of the oncological patient a necessity.

Machine Learning Analysis of Alzheimer's Disease Single-Cell RNA-Sequencing Data across Cortex and Hippocampus Regions.

Advancements in molecular biology have revolutionized our understanding of complex diseases, with Alzheimer's disease being a prime example. Single-cell sequencing, currently the most suitable technology, facilitates profoundly detailed disease analysis at the cellular level. Prior research has established that the pathology of Alzheimer's disease varies across different brain regions and cell types. In parallel, only machine learning has the capacity to address the myriad challenges presented by such studies, where the integration of large-scale data and numerous experiments is required to extract meaningful knowledge. Our methodology utilizes single-cell RNA sequencing data from healthy and Alzheimer's disease (AD) samples, focused on the cortex and hippocampus regions in mice. We designed three distinct case studies and implemented an ensemble feature selection approach through machine learning, also performing an analysis of distinct age-related datasets to unravel age-specific effects, showing differential gene expression patterns within each condition. Important evidence was reported, such as enrichment in central nervous system development and regulation of oligodendrocyte differentiation between the hippocampus and cortex of 6-month-old AD mice as well as regulation of epinephrine secretion and dendritic spine morphogenesis in 15-month-old AD mice. Our outcomes from all three of our case studies illustrate the capacity of machine learning strategies when applied to single-cell data, revealing critical insights into Alzheimer's disease.

Sex Differences in Autonomic Blood Pressure Regulation: Sex Chromosome Complement and Hormonal Involvement

Although several lines of evidence from different studies highlight sex differences in cardiovascular diseases, to date, most studies have been focused on males, with the idea that males and females are similar, differing only in the magnitude of the response. However, the principles learned in male models cannot and should not be extrapolated to women and, therefore, it is important to study in greater detail not only the differences between the sexes but also the physiological intertwining of the underlying genetic and hormonal mechanisms of sexual dimorphism. This review explores the sex disparities in the autonomic nervous system regulation of blood pressure (particularly baroreceptor function), with special emphasis on sex hormones and sex chromosome complement factors involved in sexually dimorphic autonomic blood pressure regulation. A more detailed understanding of the sources of physiological disparities between the sexes may also help in understanding the differences between the sexes in rates of cardiovascular disease and may also aid in designing future improvements for sex-tailored therapeutic treatments.

Sublethal concentrations of pymetrozine reduce Sogatella furcifera transmission of Southern rice black-streaked dwarf virus.

The transmission of plant viruses is closely associated with the specific probing behaviors of the vectors. Pymetrozine is a pyridine azomethine insecticide that interferes with nervous regulation of feeding behavior of piercing-sucking insects. This study aimed to evaluate the potential of sublethal concentrations of pymetrozine in reducing the transmission of Southern rice black-streaked dwarf virus (SRBSDV) by the planthopper Sogatella furcifera. Laboratory assays showed that both acquisition and inoculation rates of SRBSDV decreased significantly in the planthoppers feeding on plants treated with lethal concentrations 10% and 50% (LC10 and LC50 ) pymetrozine compared with the insects feeding on the control plants, for which significant effects of pymetrozine concentration and time post-treatment were detected. Honeydew excretion of the planthoppers showed significant reduction with increasing concentration of the insecticide but no significant association with time post-treatment. Electrical penetration graph recordings revealed that total durations of each waveform in both acquisition and inoculation were significantly affected by pymetrozine treatment, with total durations of non-probing (NP), penetration initiation (N1), and extracellular activity (N3) elongated whereas those of salivation (N2) and phloem-related activities (N4-a and N4-b) shortened. Additionally, both acquisition and inoculation rates were significantly lower at 168 h than at 6 h post-treatment. The results indicate that sublethal concentrations of pymetrozine reduce SRBSDV transmission, which is associated with reduction in feeding and alteration in probing behaviors characterized by the prolonged non-probing, penetration initiation and extracellular activity and shortened salivation and phloem-related activities. © 2023 Society of Chemical Industry.

The history of the Department of Pharmacology, Institute of Experimental Medicine (to the 100th anniversary of the department)

The Department of Pharmacology of the Institute of Experimental Medicine was established in the autumn of 1923 on the initiative of the institutes leadership. Professor Nikolai Pavlovich Kravkov (18651924), the most respected domestic pharmacologist at that time and the head of the Department of Pharmacology of the Military Medical Academy, was invited as the alleged head of the department. However, N.P. Kravkovs untimely death in April 1924 precluded the department from developing extensive research in Pharmacology. Professor Vladimir Vasilyevich Savich (18741936), a student of I.P. Pavlov who focused his main research on the effect of medicinal substances on the nervous regulation of the cardiovascular system, gastrointestinal tract, endocrine system, and water metabolism, led the department from 1924 to 1936. The mechanism of the direct impact of drugs and poisons on organs and tissues was studied using both isolated organs, notably endocrine glands, and classical conditioned reflex techniques. In 1936, the department was disbanded in connection with the death of the head (V.V. Savich) and the reorganization of the institutes structure. Professor S.V. Anichkov (18921981), who later became the Hero of Socialist Labor, laureate of the Lenin and State Prizes of the USSR, and academician of the USSR Academy of Medical Sciences, revived the department in 1948 and remained its permanent head until his death (in July 1981). Along with him were well-known researchers Professors V.M. Karasik, N.V. Khromov-Borisov, I.S. Zavodskaya (who led the department from 1981 to 1984), Y.S. Borodkin (who led the department from 1984 to 1992), N.A. Kharauzov, V.E. Ryzhenkov, N.S. Sapronov (who led the department from 1992 to 2011), P.P. Denisenko, and N.A. Losev. The main focus of the department from 1948 to 1984 was the integration of fundamental pharmacological advancements with the introduction of drugs into healthcare practice. Currently, the Department of Neuropharmacology. S.V. Anichkova is one of the largest research centers in Russia, focusing on fundamental research in Pharmacology. Professor P.D. Shabanov has been the head of the department since 2011. The department divided into four laboratories: the Laboratory of Chemistry and Pharmacology of Medicinal Products (led by Doctor of Medical Sciences, E.R. Bychkov), the Laboratory of General Pharmacology (led by Doctor of Biological Sciences, Prof. A.A. Lebedev), the Laboratory of Biochemical Pharmacology (led by Doctor of Medical Sciences, Prof. P.D. Shabanov), and the Laboratory of Synthesis and Nanotechnology of Medicinal Substances (led by Doctor of Biological Sciences, Prof. L.B. Piotrovsky).

The Nervous System Development Regulator Neuropilin-1 as a Potential Prognostic Marker and Therapeutic Target in Brain Cancer.

Neuropilins are transmembrane glycoproteins that regulate developmental processes in the nervous system and other tissues. Overexpression of neuropilin-1 (NRP1) occurs in many solid tumor types and, in several instances, may predict patient outcome in terms of overall survival. Experimental inhibition of NRP1 activity can display antitumor effects in different cancer models. Here, we review NRP1 expression and function in adult and pediatric brain cancers, particularly glioblastomas (GBMs) and medulloblastomas, and present analyses of NRP1 transcript levels and their association with patient survival in GBMs. The case of NRP1 highlights the potential of regulators of neurodevelopment as biomarkers and therapeutic targets in brain cancer.

Health implications forecast for electronic cigarette users

Electronic cigarettes have rapidly gained popularity in the tobacco market, primarily among young adults. Marketers exploit the lack of evidence regarding their health effects and label them as a safe alternative to traditional cigarettes. Our study aims to expand the existing body of evidence on their impact on the human body. Objective: To identify the most significant characteristics of individuals using electronic cigarettes based on statistical analysis of clinical and laboratory examination data. Materials and Methods. The study included 102 participants (main group – 66 individuals using electronic cigarettes as an alternative form of smoking; control group – 36 individuals who did not use electronic or industrial cigarettes) aged 20 to 35 years. Each participant provided written informed consent to participate. Patient examinations included the following parameters: height, weight, body mass index (BMI) calculation; measurement of blood pressure, heart rate, pulse, and respiratory rate; throat swab collection. Results. According to our data, individuals in the main group had higher height, weight, and BMI values. A higher BMI may be associated with excessive stimulation of salivary glands and, consequently, increased gastric secretion and appetite stimulation. Electronic cigarette users had significantly higher blood pressure levels compared to the control group. Users of nicotine delivery systems in throat swabs had significantly higher levels of mucus, coccal flora, and neutrophil percentage, indicating the presence of bacterial agents in the oral cavity mucosa. This may be related to bacterial agents’ dissemination through nicotine delivery devices. We conducted multiple logistic regression analysis with potential patient characteristics. Conclusions. Electronic cigarette users are characterized by higher height, weight, BMI, blood pressure levels compared to non-smoking peers, as well as reduced adaptation potential and a prevalence of parasympathetic nervous system regulation. It was found that a typical electronic cigarette user is a male (OR = 15.9364) with reduced IFZ – adaptive potential of functional abilities (OR = 7.8128) and an abnormal amount of oral cavity flora (OR = 1.7748).

The value of some indices of heart rate variability in the diagnosis of fetal growth retardation

Fetal growth retardation (FGR) is one of the most serious problems in current perinatology. This pathology leads not only to the deterioration of perinatal outcomes but also significantly increases morbidity during adult life. FGR is known to be featured by its delayed “neurological maturation”. This is manifested in a decrease in autonomic nervous regulation according to the fetal heart rate variability (HRV) scores and indices. The objective: to study HRV in fetuses with normal biometric indices compared to similar parameters of growth retarded fetuses. Materials and methods. The 47 pregnant women who had fetuses with normal biometric indices (I group) and 33 patients with fetal growth retardation (II group) were included in the study. The investigation of the fetal HRV was performed by processing the R–R intervals obtained via non-invasive electrocardiogram (ECG) and involved the following indices: STV (short term variations), LTV (long term variations), AC/DC (acceleration capacity/deceleration capacity), TP (total power), SI (stress index), SDNN (standard deviation of normal to normal intervals), EnRE (entropy of the time series), D2 (correlation dimension of the time series), Z (temporary irreversibility) і FL (measure of fuzzy logic, integrated measure of HRV). Results. The obtained data indicated that the indices of fetal HRV were reduced in the patients with FGR. These indices have utility in screening programs for the detection of fetal intrauterine nutrition and growth disturbances. The results of the study allow us to believe that the ability to accelerate heart rate patterns is partly preserved even during FGR. This may indicate a very ancient phylogenetic nature of the reaction of the heart system of the fetus to its motile activity. However, decelerations according to the DC were typical for FGR. A non-invasive fetal ECG could become a useful supplementary method in the current methods’ spectrum used in perinatal medicine. Conclusions. Therefore, the development of algorithms for the diagnosis of FGR requires the inclusion of the following HRV indices: STV, LTV, DC, TP, SI, SDNN, D2, Z, and FL. These biophysical markers of FGR can be used as a screening program in conditions of lack of access to high-quality ultrasound diagnostics or be a valuable addition to existing perinatal strategies.

Lifetide biofeedback intervention in type 2 diabetic patients: a pilot observation

To evaluate the therapeutic efficacy of lifetide biofeedback intervention in patients with type 2 diabetes mellitus (T2DM). We analyzed the changes in average blood glucose, estimated glycosylated hemoglobin (HbA1c), fasting blood glucose and HbA1c levels in 5 patients with T2DM undergoing lifetide biofeedback intervention without the use of hypoglycemic drugs. A transient blood glucose monitoring system was used for drug withdrawal management during the intervention. Compared with those before the intervention, the average blood glucose and fasting blood glucose and HbA1c levels showed no significant changes after the intervention without using hypoglycemic drugs (P>0.05), but the estimated HbA1c was significantly decreased after the intervention (P<0.05). Two patients achieved complete remission, two showed partial remission, and one had substantially improved blood glucose levels. One patient showed a marked increase in extremity temperature after the intervention (P<0.05). Another patient had a significantly increased heart rate variability index (P<0.05) without obvious changes in heart rate after the intervention (P>0.05). By reestablishing the balance in autonomic nervous system regulation and enhancing peripheral microcirculation, lifetide biofeedback intervention helps to maintain stable blood glucose levels, achieve disease remission, and reduce the occurrence of complications in T2DM patients after discontinuation of hypoglycemic drugs without changing their lifestyles.

Neural control of the circulation during exercise in heart failure with reduced and preserved ejection fraction.

Patients with heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF) exhibit severe exercise intolerance that may be due, in part, to inappropriate cardiovascular and hemodynamic adjustments to exercise. Several neural mechanisms and locally released vasoactive substances work in concert through complex interactions to ensure proper adjustments to meet the metabolic demands of the contracting skeletal muscle. Specifically, accumulating evidence suggests that disease-related alterations in neural mechanisms (e.g., central command, exercise pressor reflex, arterial baroreflex, and cardiopulmonary baroreflex) contribute to heightened sympathetic activation and impaired ability to attenuate sympathetic vasoconstrictor responsiveness that may contribute to reduced skeletal muscle blood flow and severe exercise intolerance in patients with HFrEF. In contrast, little is known regarding these important aspects of physiology in patients with HFpEF, though emerging data reveal heightened sympathetic activation and attenuated skeletal muscle blood flow during exercise in this patient population that may be attributable to dysregulated neural control of the circulation. The overall goal of this review is to provide a brief overview of the current understanding of disease-related alterations in the integrative neural cardiovascular responses to exercise in both HFrEF and HFpEF phenotypes, with a focus on sympathetic nervous system regulation during exercise.

Determination of heart rate variability as an indicator of the influence of the tone of the autonomic nervous system in goats

The relevance of the topic lies in the studied role of the autonomic nervous system in regulating the cardiovascular system in goats. The variability of the heart rate is a good indicator in the study of the animal's health quality and the analysis of its psychophysiological state in the farm. The purpose of the study is to establish the influence of the tone of autonomous nervous regulation on the body of goats, which is reflected in changes in the sympatho-vagal balance. Experimental studies were carried out on goats of the Zaanenska breed. A cardiograph was used to diagnose the variability of the heart rate, followed by the determination of the main indicators according to Baevsky's method, which included the determination of mode, mode amplitude, variation range, autonomic balance index, autonomic rhythm index, and stress index. Based on the results of the study, three research groups were formed: normotonics, vagotonics, and sympathotonics. Sympathotonic animals had high values of heart rate 96.80 ± 6.62, intensity of the R-R interval 35.30 ± 1.18, and low values of the value of the R-R interval 0.63 ± 0.04 (Р ≤ 0.05; Р ≤ 0.001). Vagotonic goats had the opposite features, characterized by a decrease in heart rate 58.4 ± 2.21, the intensity of the R-R interval 12.44 ± 1.11, and an increase in the value of the R-R interval 1.03 ± 0.04 (Р ≤ 0.01; Р ≤ 0.001). Normotonic animals, compared to other experimental groups, had average values. Based on the obtained results, goats, depending on the influence of the tone of the autonomic nervous system, have differences in the activity of the cardiovascular system. Due to this, their response to the stress factor will differ, which in turn will affect productivity. Determination of heart rate variability can become one of the indispensable indicators in the analysis of animal health on dairy farms. Therefore, this question is quite relevant, especially when studying the metabolic processes of the body of goats, to improve the efficiency of productivity while preserving the physiological state of the animal.

INDICATORS OF CIRCUITAL HEART RHYTHM IN SCHOOLCHILDREN WITH CARDIAC NEUROCERCULATORY DYSTONIA RESIDING IN THE ANDIJAN REGION

Annotation. According to the international systematization of diseases (10th revision), neurocirculatory dystonia (NCD) refers to somatoform autonomic dysfunction that occurs with a violation of the nervous regulation of the circulatory system. Among non-infectious diseases of childhood and adolescence, vegetative-vascular dystonia is considered the most common pathology with a frequency of 4.8 to 29.1%. It is known that vegetative-vascular dystonia or its variant neurocircular dystonia is considered a predictor of arterial hypertension, atherosclerosis and coronary heart disease at a young age. Currently, determination of heart rate variability (HRV) is recognized as the most informative non-invasive method for quantitative assessment of the autonomic regulation of heart rate. The purpose of the study was a comparative assessment of the variability of circadian rhythm and heart rate in adolescents with similar neurocirculatory dystonia living in urban and rural areas. Materials and methods. We examined 77 adolescents aged 12 to 17 years (average age 14.5±0.35 years, boys -31, girls -46), hospitalized with a diagnosis of somatoform autonomic dysfunction, cardiac type NCD, from January 2022 to February 2023. Information is classified by age and place of residence (urban, rural). Taking into account the mechanisms of development of the autonomic nervous system, 2 age groups were identified. 1st age group - children 12-14 years old 49.5±4.99% (average age 13.4±0.24 years), of which 62.5±8.83% lived in Andijan (group IA), 37.5±11.74% of adolescents - in rural areas of Andijan region (group IB). 2nd age group - teenagers 15-17 years old 50.5±4.99% (average age 16.5±0.29), of which 61.2±8.89% of young people lived in Andijan (group IIA), 38.8±11.49% - in rural areas (group IIB). All teenagers live in the Andijan region every day. Results. Among the examined adolescents with NCD of the heart, complaints of pain in the heart area were similar (in age group I - 70.8±6.56%, in age group II - in 83.7±5.28% of those examined). The pain was mostly temporary (lasting a few seconds) and stabbing in nature. Interruptions in heart function were noted by 43.8±7.16% of young people in group I and 55.1±7.11% of young people in age group II. In addition, 31.3±6.69% of adolescents in age group I and 36.7±6.89% of young people in group II complained of headache, dizziness, impotence, and excessive fatigue. Conclusions. When examining adolescents with neurocirculatory dystonia, it is necessary to conduct not only a normal ECG at rest, but also Holter ECG monitoring with determination of heart rate variability; the examination will ensure adequate treatment and monitoring of this group of patients. The detected changes in the circadian rhythm and rhythm variability in urban adolescents compared to rural ones are probably associated with living in an industrial zone, environmental criteria, nutrition, and an even greater information load, which urgently requires further research.

Adaptation of functional systems in different generations of Caucasians in the North-East of Russia

BACKGROUND: A substantial body of research has focused on adaptation of the new residents of the European and Asian Far North. However, these publications fail to address the changes occurring in successive generations of native Caucasians who migrated to the regions with harsh climatic conditions.&#x0D; AIM: To study functional adaptations exhibited by individuals born in the Magadan Region to various generations of Caucasians permanently living in the area.&#x0D; METHODS: A total of 1632 male volunteers, all students aged 181.1 years, and of Caucasian ethnicity, participated in this study. These individuals were either migrants or residents of Russia's North-East, born within the first to third generations. We investigated anthropometric characteristics, cardiohemodynamic parameters, and gas exchange to understand the adaptive readjustments that take place within the body's functional systems.&#x0D; RESULTS: Migrants and first-generation residents in the Magadan region experience constant stress and inadequate functioning of their cardiohemodynamic and energy exchange systems under extreme conditions. However, the third-generation subjects exhibited optimal performance of the cardiovascular system. Remarkably, the third-generation residents demonstrate an increased systolic volume at lower arterial pressure and lower total peripheral resistance. Furthermore, they had elevated proportion of the high frequency component and total power of the heart rhythm spectrum. This represents a new level of changed influence on the heart rhythm, as seen in the altered balance of its statistical and spectral wave characteristics. Moreover, the adaptability of the cardiovascular system to the harsh conditions of the North is reflected not only in the physiological indicators of the body but also in the integral structure of their correlations. This includes the magnitude and sign of the correlation coefficients and their significance.&#x0D; CONCLUSIONS: Our main findings suggest that adaptive changes in cardiohemodynamic and gas exchange exhibited by the migrants and several generations of residents of the Far North-East of Russia are directed to minimization of the total energy expenditure in functional systems. Additionally, the parasympathetic contribution increases fostering a novel interaction between the components of autonomic nervous regulation reflected by both qualitative and quantitative alterations in the structure and patterns of correlation clusters. These findings contribute to our understanding of the physiological mechanisms behind the morphofunctional readjustments of Caucasian men in the process of adaptation to the harsh climatic conditions of the Russian North-East.

Polysaccharide from Paris polyphylla improves learning and memory ability in D-galactose-induced aging model mice based on antioxidation, p19/p53/p21, and Wnt/β-catenin signaling pathways

The current study aimed to investigate the effects and mechanisms of Paris polyphylla polysaccharide component 1 (PPPm-1) to improve learning and memory in D-galactose-induced aging model mice. We determined the effects of PPPm-1 on the brain, organ index, and behavior in the aging model mice induced by D-galactose to study learning and memory improvement. UV–Vis spectrophotometry helped determine the PPPm-1 effect on antioxidant parameters associated with learning and memory in the brain and related organs of aging mice. Moreover, in the hippocampi of aging model mice, PPPm-1 effect on the mRNA and protein expressions of p19, p53, p21, P16, Rb, Wnt/1, β-catenin, CyclinD1, TCF-4, and GSK-3β were detected using the quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The results indicated that PPPm-1 could increase the brain and organ indexes, the avoidance latency, the total distance and average speed in the water maze, and the SOD and GSH-PX activities in the brain, liver tissues, and plasma. Moreover, the mRNA and protein expressions of Wnt/1, β-catenin, CyclinD1, and TCF-4 were also elevated in the hippocampi of aging model mice. However, the error times in step-through tests, the MDA content in the brain and liver tissues, the AChE activity in the brain tissue, the protein expressions of P16, Rb in the hippocampi, and the mRNA and protein expressions of p19, p53, p21, and GSK-3β in the hippocampi of aging model mice were significantly decreased. Thus, PPPm-1 significantly enhanced the learning and memory impairment induced by D-galactose in mice. The action mechanisms were associated with anti-oxidative stress, cholinergic nervous system function regulation, LTP enhancement in long-term memory, down-regulated expression of p19/p53/p21 signaling pathway factors, and Wnt/β-catenin signaling pathway activation.

Tributyl phosphate can inhibit the feeding behavior of rotifers by altering the axoneme structure, neuronal coordination and energy supply required for motile cilia

Organophosphorus flame retardants (OPFRs) are frequently detected in aquatic environments and can potentially amplify the food chain, posing a potential risk to organisms. Marine invertebrates have primitive nervous systems to regulate behavior, but how they respond to OPFRs that are potentially neurotoxic substances is unclear. This study assessed changes in the feeding behavior of rotifer Brachionus plicatilis exposed to alkyl OPFRs tributyl phosphate (TnBP) (0.376 nM, 3.76 and 22.53 µM) to elucidate the mechanism of behavioral toxicity. TnBP at 22.53 μM reduced the ingestion and filtration rates of rotifers for Chlorella vulgaris and Phaeocystis globosa in a 24-h test and altered rotifer-P. globosa population dynamics in 15-d coculture. Ciliary beat frequency was also reduced, and the expression of genes encoding the cilia axoneme was downregulated. TnBP could inhibit rotifer acetylcholinesterase activity by binding this protein and reduce the expression of the exocytotic membrane protein syntaxin-4, suggesting a disorder in nervous regulation of cilia beat. Moreover, TnBP induced abnormal shape and dysfunction of mitochondria, which caused insufficient energy required for ciliary movement. This study revealed diverse neurotoxicity mechanisms of TnBP, particularly as a potentially competing acetylcholinesterase ligand for aquatic invertebrates. Our research also provides a meaningful reference for OPFR-induced behavioral toxicity assessments.