Metabolic System Research Articles

Maternal under-nutrition during pregnancy alters the molecular response to over-nutrition in multiple organs and tissues in nonhuman primate juvenile offspring.

Previous studies in rodents suggest that mismatch between fetal and postnatal nutrition predisposes individuals to metabolic diseases. We hypothesized that in nonhuman primates (NHP), fetal programming of maternal undernutrition (MUN) persists postnatally with a dietary mismatch altering metabolic molecular systems that precede standard clinical measures. We used unbiased molecular approaches to examine response to a high fat, high-carbohydrate diet plus sugar drink (HFCS) challenge in NHP juvenile offspring of MUN pregnancies compared with controls (CON). Pregnant baboons were fed ad libitum (CON) or 30% calorie reduction from 0.16 gestation through lactation; weaned offspring were fed chow ad libitum. MUN offspring were growth restricted at birth. Liver, omental fat, and skeletal muscle gene expression, and liver glycogen, muscle mitochondria, and fat cell size were quantified. Before challenge, MUN offspring had lower body mass index (BMI) and liver glycogen, and consumed more sugar drink than CON. After HFCS challenge, MUN and CON BMIs were similar. Molecular analyses showed HFCS response differences between CON and MUN for muscle and liver, including hepatic splicing and unfolded protein response. Altered liver signaling pathways and glycogen content between MUN and CON at baseline indicate in utero programming persists in MUN juveniles. MUN catchup growth during consumption of HFCS suggests increased risk of obesity, diabetes, and cardiovascular disease. Greater sugar drink consumption in MUN demonstrates altered appetitive drive due to programming. Differences in blood leptin, liver glycogen, and tissue-specific molecular response to HFCS suggest MUN significantly impacts juvenile offspring ability to manage an energy rich diet.

Transcriptome analysis of mammary epithelial cell between Sewa sheep and East FriEsian sheep from different localities.

Mammary epithelial cells, the only milk-producing cell type in the mammary gland, undergo dynamic proliferation and differentiation during pregnancy, culminating in lactation postpartum. The East FriEsian sheep ranks among the world's most prolific dairy breeds, while the Sewa sheep, a unique dual-purpose breed autochthonous to the Qinghai-Tibet Plateau, exhibits significantly lower milk production. Employing tissue culture methods, we successfully established mammary epithelial cell lines from both breeds. Morphological assessment of mammary epithelial cells and immunofluorescence identification of Cytokeratin 7 and Cytokeratin 8 confirmed the epithelial identity of the isolated cells. Subsequent RNA-seq analysis of these in vitro epithelial cell lines revealed 1813 differentially expressed genes (DEGs). Among these, 1108 were significantly up-regulated and 705 were down-regulated in Sewa epithelial sheep cells compared to East FriEsian epithelial cells. KEGG enrichment analysis identified cellular processes, environmental information processing, human diseases, metabolism, and organismal systems as the primary functional categories associated with DEGs. Gene ontology (GO) terms annotation, categorized into molecular function, biological processes, and cellular component, yielded "binding and catalytic activity," "molecular function regulator activity," and "cellular process," "biological regulation," and "regulation of biological process" as the top three terms within each domain, respectively. Clusters of Orthologous Groups of proteins (KOG) classification further revealed that "signal transduction mechanisms" accounted for the largest proportion of DEGs among all KOG categories. Finally, based on these analyses, ATF3 and MPP7 were identified as promising candidate genes for regulating lactation.

Incidence, risk factors for metabolic syndrome and health systems capacity for its management amongst people living with HIV, Accra-Ghana: A study protocol.

Metabolic syndrome (MetS) refers to the clustering of three or more metabolic disorders including high blood pressure, glucose impairment, abdominal obesity, high triglycerides, and low high-density lipoproteins. MetS is increasingly being considered an epidemic among People Living With HIV (PLWH) with reports of association between HIV infection and/or antiretroviral therapy (ART) usage and development of MetS. MetS predisposes PLWH to the development of cardiovascular, kidney diseases and diabetes, decreases the quality of life, and burdens the health system. This study aims to establish the incidence, time to development and risk factors for development of MetS and it's components, and to assess the capacity of the health system to manage MetS and it's components among ART naive PLWH in Accra, Ghana. We will conduct a mixed methods study with quantitative and qualitative data collection. Our prospective cohort study would enroll adults of 18 years and above with none or less than three MetS components at baseline and follow them up at six months and one year. Demographic, lifestyle data, anthropometric, and laboratory data will be collected using an adapted WHO Steps Survey questionnaire. The WHO Service Availability and Readiness Questionnaire (SARA) will be adapted to collect information on capacity across the six WHO building blocks. Key informant interviews will be conducted with HIV coordinators at the national, regional, and facility levels. In-depth interviews will be conducted with PLWH from the cohort who develop MetS or MetS components during their follow-up. Data will be analysed using proportions, Kaplan Mier time to event analysis, fitting of Cox proportional hazard regression models for risk factors, and generation of themes from qualitative data. This study will generate data on the incidence, time to development, risk factors for MetS and MetS components development, and health systems capacity for MetS management among PLWH. Findings would inform revisions to the guidelines and policies for HIV care in Ghana, Africa, and beyond, ultimately improving MetS prevention and management among the vulnerable population of PLWH.

Integration and Analysis of Omics Data Using Genome-Scale Metabolic Models

Constraint-based modelling and genome-scale metabolic models (GEMs) have been used extensively to analyze omics data, providing a mechanistic perspective on complex metabolic systems and networks [...]

Glucose Metabolism and Sex Hormones in Male Patients with Medication-naïve First-episode Schizophrenia: A Large-scale Cross-sectional Study.

Schizophrenia (SCZ) usually begins in early adult life. The underlying molecular mechanisms of SCZ remain unclear. There is evidence for the involvement of abnormalities in metabolic and endocrine systems in SCZ, even in drug-naïve first-episode schizophrenia patients (DNFES). However, the association between impaired regulation of glucose metabolism and sex hormones was not studied in SCZ. This study aimed to evaluate the interrelationship between sex hormones and high fasting glucose levels in male DNFES patients. A total of 99 patients with SCZ were recruited, and fasting glucose, fasting insulin, the insulin resistance index (HOMA-IR), and sex hormones were measured. We found that some male patients with SCZ had abnormal levels in glucose metabolism parameters and gonadal hormones that were not within the normal range. Linear regression analysis adjusted for age, waist circumference, and body mass index showed that testosterone levels were negatively associated with fasting insulin in male patients (β = -0.21, t = -2.2, p = 0.03). Our findings confirm the abnormalities in glucose metabolism parameters and gonadal hormones at the onset of the illness in male DNFES patients with SCZ. In addition, there was an interaction effect between abnormal glucose metabolism and sex hormones in male patients.

Exploring the role of genetic variability and exposure to bisphenols and parabens on excess body weight in Spanish children

Gene-environment interaction studies are emerging as a promising tool to shed light on the reasons for the rapid increase in excess body weight (overweight and obesity). We aimed to investigate the influence of several polymorphisms on excess weight in Spanish children according to a short- and long-term exposure to bisphenols and parabens, combining individual approach with the joint effect of them. This case-control study included 144 controls and 98 cases children aged 3-12 years. Thirty SNPs in genes involved in obesity-related pathways, xenobiotic metabolism and hormone systems were genotyped using the GSA microchip technology and qPCRs with Taqman® probes. Levels of bisphenols and parabens in urine and hair were used to assess short- and long-term exposure, respectively, via UHPLC-MS/MS system. LEPR rs9436303 was identified as a relevant risk variant for excess weight (ORDom:AAvsAG+GG=2.65, p<0.001), and this effect persisted across exposure-stratified models. For long-term exposure, GPX1 rs1050450 was associated with increased excess weight at low single paraben exposure (ORGvsA=2.00, p=0.028, p-interaction=0.016), whereas LEPR rs1137101 exhibited a protective function at high co-exposure (ORDom:AAvsAG+GG=0.17, p=0.007, p-interaction=0.043). ESR2 rs3020450 (ORDom:GGvsAG+AA=5.17, p=0.020, p-interaction=0.028) and CYP2C19 rs4244285 (ORDom:GGvsAG+AA=3.54, p=0.039, p-interaction=0.285) were identified as predisposing variants at low and high co-exposure, respectively. In short-term exposure, higher odds were observed for INSIG2 rs7566605 at high bisphenol exposure (ORCvsG=2.97, p=0.035, p-interaction=0.017) and for GSTP1 rs1695 at low levels (ORDom:AAvsAG+GG=5.38, p=0.016, p-interaction=0.016). At low and medium co-exposure, SH2B1 rs7498665 (ORAvsG=0.17, p=0.015, p-interaction=0.085) and MC4R rs17782313 (ORAvsG=0.10, p=0.023, p-interaction=0.045) displayed a protective effect, whereas ESR2 rs3020450 maintained its contributing role (ORGvsA=3.12, p=0.030, p-interaction=0.010). Our findings demonstrate for the first time that understanding the genetic variation in excess weight and how the level of exposure to bisphenols and parabens might interact with it, is crucial for a more in-depth comprehension of the complex polygenic and multifactorial aetiology of overweight and obesity.

Sex dimorphism and tissue specificity of gene expression changes in aging mice

BackgroundAging is a complex process that involves all tissues in an organism and shows sex dimorphism. While transcriptional changes in aging have been well characterized, the majority of studies have focused on a single sex and sex differences in gene expression in aging are poorly understood. In this study, we explore sex dimorphism in gene expression in aging mice across three tissues.MethodsWe collected gastrocnemius muscle, liver and white adipose tissue from young (6 months, n = 14) and old (24 months, n = 14) female and male C57BL/6NIA mice and performed RNA-seq. To investigate sex dimorphism in aging, we considered two levels of comparisons: (a) differentially expressed genes between females and males in the old age group and (b) comparisons between females and males across the aging process. We utilized differential expression analysis and gene feature selection to investigate candidate genes. Gene set enrichment analysis was performed to identify candidate molecular pathways. Furthermore, we performed a co-expression network analysis and chose the gene module(s) associated with aging independent of sex or tissue-type.ResultsWe identified both tissue-specific and tissue-independent genes associated with sex dimorphism in aged mice. Unique differentially expressed genes between old males and females across tissues were mainly enriched for pathways related to specific tissue function. We found similar results when exploring sex differences in the aging process, with the exception that in the liver genes enriched for lipid metabolism and digestive system were identified in both females and males. Combining enriched pathways across analyses, we identified amino acid metabolism, digestive system, and lipid metabolism as the core mechanisms of sex dimorphism in aging. Although the vast majority of age-related genes were sex and tissue specific, we identified 127 hub genes contributing to aging independent of sex and tissue that were enriched for the immune system and signal transduction.ConclusionsThere are clear sex differences in gene expression in aging across liver, muscle and white adipose. Core pathways, including amino acid metabolism, digestive system and lipid metabolism, contribute to sex differences in aging.

The Role of Gut Microbioma in Human Health: Exploring the Impact on Metabolism, Immunity, and Neurological Disorders

Abstract: The human microbiota has been progressively accepted for its role in sustaining overall health and well-being. The gut microflora vigorously communicates with the host metabolic system that exert influence on the progression, maturation, immune cells development and immune homeostasis maintenance. For the proper functioning of the immune system a diversified and steady gut microflora is needed, while “Dysbiosis” or an imbalance in the gut microbioma will lead to autoimmune and inflammatory diseases. The gut microbiota provides shape to our immune response and contribute to host protection against pathogen or bacterium through mechanisms such as the transformation of pro- inflammatory cytokine production, regulatory T-cell inductor and by intestinal mucosaql barrier. In addition to gut microbiota can affect our neurological function and play a key role in the pathogenesis of psychological disorders such as autism, depression, anxiety, Parkinson and Alzheimer’s disease. Gut microbiota can regulate neurological disorders by supplementing them with fecal transplantation, probiotics and antibiotics. An important parameter to consider gut microbioma disorder is Firmicutes/ Bacteroidetes.

Editorial for the Special Issue “Oxidative Stress, Inflammation and Antioxidant Defense System in Psychiatric Disorders” in Antioxidants (2022–2023)

A growing body of evidence indicates that many genetic and environmental factors associated with psychiatric disorders affect redox homeostasis, mitochondria and energy metabolism, and neuroendocrine and immune systems in a complex synergistic manner, leading to oxidative stress and inflammation [...]

Zinc oxide nanoparticles at low dose mitigate lead toxicity in pea (Pisum sativum L.) seeds during germination by modulating metabolic and cellular defense systems

Addressing lead (Pb) pollution and contamination in soil and agriculture is urgent due to its widespread and long-lasting impacts on human health, food safety, and the environment. In the current study, we assessed the potential use of Zinc oxide nanoparticles (ZnONPs) in alleviating Pb toxicity in germinating seedlings. Pea (Pisum sativum L.) seedlings were exposed to Pb (83 mg/L) over a 7-day period, without and with ZnONPs amendment. Our results showed that the application of ZnONPs at 10 mg/L restored the morphological parameters affected by Pb, 34 %, 26 % and 23 %, for the length, fresh, and dry biomass of embryonic axis, respectively. ZnONPs decreased the activities of antioxidative enzymes of catalase (87.5 %), guaiacol peroxidase (60 %), and glutathione peroxidase (25 %), but increased the activities of ascorbate peroxidase (60 %) and glutathione reductase (25 %). These changes were associated with the increase (7 %) in the thiol groups, and reductions in the malondialdehyde (23 %), hydrogen peroxide (33 %), and carbonyl group levels (78 %), in addition to the stimulation of the activities of ROS-associated enzymes, including glycolate oxidase (40 %) and NADPH oxidase (by 89 %). Consequently, cell viability was increased by 66 %, while cellular death was reduced by 10 %, with ZnONPs, relative to the Pb-stressed seedlings. These findings highlight the mechanisms surrounding the ability of nanosized ZnO to mitigate the harmful effects of Pb on the growth and physiology of plants. Further investigation is needed to understand the mitigating effects of ZnONPs on Pb on the molecular and genomic levels in seedlings and plants, and ensure the sustainability of agricultural practices and food safety. Besides, site and source-specific integrated approaches must be practiced to formulate suitable remediation strategies.

Ketogenic Diet and Endocrine and Metabolic Diseases: A Bibliometric Study and Visualization Analysis.

The ketogenic diet, known for its high-fat, low-carbohydrate composition, has been extensively studied in endocrine and metabolic diseases. This study carried out bibliometric analysis to examine the research trends in this field over the past 20 years, aiming to provide insights for future studies. We searched the Web of Science Core Collection for all relevant papers. VOSviewer was used for network visualization, the bibliometrix package of R software (version 4.3.0) was utilized for data analysis, and CiteSpace was employed for mapping and trend analysis. This study encompassed 508 relevant articles spanning from 2003 to 2023, authored by 2827 researchers from 887 institutions across 57 countries/regions. The total number of publications increased from 3 in 2003 to 508 in 2023, showing a steady growth trend. The United States emerged as the predominant contributor in this field, followed by Italy and China. Notably, SAJOUX I consistently exhibited high activity in this field, according to the analysis, with an h-index of 13. The journal Nutrients has consistently made substantial contributions to this field, accounting for 19% of all publications. The keywords "obesity," "ketogenic diet," and "weight loss" appeared most frequently, with "obesity" occurring 163 times. This study used a bibliometric method to analyze the impact of the ketogenic diet on the endocrine metabolic system. The research identifies recent frontiers and trending directions, providing valuable references for scholars in this field.

Age Differences and Prevalence of Comorbidities for Death and Survival in Patients with COVID-19: A Single-Center Observational Study in a Region of Southern Italy

The SARS-CoV-2 outbreak has resulted in a considerable number of deaths worldwide. The virus damages the pulmonary artery endothelium, leading to a condition known as microvascular pulmonary inflammatory thrombotic syndrome (MPITS), which can be fatal and cause multiple organ failure. The presence of preexisting comorbidities has been shown to significantly impact the severity and prognosis of patients with SARS-CoV-2 infection. The objective of this study was to compare the age groups of patients with coronavirus disease 2019 (COVID-19) and to identify the prevalence of comorbidities associated with death and survival in an area of southern Italy. The data set consisted of 1985 patients with confirmed cases of SARS-CoV-2 infection who were admitted to the A.O.U. San Giovanni di Dio e Ruggi d’Aragona Hospital in Salerno between January 2021 and December 2022. The results were presented for the overall population and stratified by outcome and age group. All analyses were performed using the XLSTAT (Lumivero, 2024, Paris, France) and STATA software (release 16.1, StataCorp LLG, College Station, TX, USA, 2019) packages. In the study, population, 636 cases (32%) resulted in death, with a higher prevalence in the 60–79 age group, followed by the ≥80 and 30–59 age groups. The most prevalent diseases among deceased and surviving patients with confirmed cases of SARS-CoV-2 infection were those affecting the circulatory system (61.5% vs. 55.5%), the respiratory system (55.8% vs. 26.2%), and the metabolic system (25.9% vs. 25.4%). In patients aged 30–79, respiratory diseases were the primary cause of mortality, whereas in those aged ≥80, circulatory system diseases were more prevalent. Among survivors, cardiovascular diseases were the most common comorbidities across all age groups, followed by respiratory diseases and endocrine, metabolic, and immune disorders. Moreover, these comorbidities were associated with an elevated risk of mortality. The study emphasizes the substantial influence of age and comorbidities on the mortality associated with SARS-CoC-2 infection. These findings highlight the necessity for targeted interventions to manage comorbid conditions in patients with SARS-CoV-2 infection, particularly in older adults.

Urinary biochemical ecology reveals microbiome-metabolite interactions and metabolic markers of recurrent urinary tract infection.

Recurrent urinary tract infections (rUTIs) are a major clinical challenge in postmenopausal women and their increasing prevalence underscores the need to define interactions between the host and the urinary microbiome that may underlie rUTI susceptibility. A body of work has identified the taxonomic profile of the female urinary microbiome associate with aging, menopause, and urinay disease. However, how this microbial community engages with the host niche, including the local biochemical environment of the urogenital tract, in health and disease is yet to be fully defined. This study directly assesses differences in the biochemical environment of the urine, or biochemical ecology, associated with recurrent urinary tract infection (UTI) and defines a microbe-metabolite association network of the female urinary microbiome. By integrating metagenomic and metabolomic data collected from a controlled cohort of women with rUTI, we find that distinct metabolites, such as methionine sulfoxide (Met-SO) and trimethylamine oxide (TMAO), are associated with differences in urinary microbiome diversity. We observe associations between microbial and biochemical beta diversity and unique metabolic networks of uropathogenic Escherichia coli and uroprotective Lactobacillus species, highlighting potential metabolite-driven ecological shifts that may influence UTI susceptibility. We identify a urinary lipid signature of active rUTI that can accurately distinguish (AUC = 0.987) cases controls. Finally, using time-to-relapse data we identify deoxycholic acid (DCA) as a new prognostic indicator for rUTI recurrence. Together these findings suggest that systemic metabolic processes may influence susceptibility, opening new avenues for therapeutic intervention and the development of more accurate diagnostic and prognostic to improve patient outcomes.

Indices of carbohydrate metabolism and antioxidant system state during germination of aged wheat and triticale seeds treated with H(2)S donor

Hydrogen sulfide is a gasotransmitter molecule involved in the realization of many functions of the plant organism, including seed germination. Aging of seeds is shown to be accompanied by oxidative stress and reduced germination. The effect of exogenous hydrogen sulfide on the germination of aged cereal seeds has not been studied. The aim of the work was to estimate the effect of priming with NaHS as an H2S donor on wheat and triticale seeds previously subjected to natural aging. Seeds of winter wheat (Triticum aestivum) and winter ×Triticosecale were stored indoors for 4 years at fluctuating temperature and humidity. Aged seeds were treated with 0.2-5 mM NaHS solution for 3 h and germinated in Petri dishes for 3 days. The hydropriming­ treatment was used as a control. Amylase activity in grains, the biomass of shoots and roots, the content of total sugars, H2O2, lipid peroxidation products and anthocyanin, and the activity of antioxidant enzymes in seedlings were determined. It was shown that after the treatment with H2S donor, the activities of catalase and guaiacol peroxidase, as well as the content of anthocyanins were increased only in triticale seedlings. Nevertheless, treatment of seeds of both cereal species was followed by enhanced growth of shoots and roots, increase in amylase and superoxide dismutase activities, decrease in H2O2 and MDA contents, and elevated accumulation of sugars in shoots. It is concluded that the increase in germination of aged cereal seeds under the influence of H2S donor is caused by increased mobilization of reserve carbohydrates and modulation of antioxidant system activity. Such treatment can be considered as an effective tool to improve seedling growth. Keywords: amylase, antioxidant system, hydrogen sulfide, oxidative stress, seeds aging, total sugar, Triticosecale, Triticum aestivum

Comparative genomics of the world's smallest mammals reveals links to echolocation, metabolism, and body size plasticity.

Originating 30 million years ago, shrews (Soricidae) have diversified into around 400 species worldwide. Shrews display a wide array-array of adaptations, with some species having developed distinctive traits such as echolocation, underwater diving, and venomous saliva. Accordingly, these tiny insectivores are ideal to study the genomic mechanisms of evolution and adaptation. We conducted a comparative genomic analysis of four shrew species and 16 other mammals to identify genomic variations unique to shrews. Using two existing shrew genomes and two de novo assemblies for the maritime (Sorex maritimensis) and smoky (S. fumeus) shrews, we identified mutations in conserved regions of the genomes, also known as accelerated regions, gene families that underwent significant expansion, and positively selected genes. Our analyses unveiled shrew-specific genomic variants in genes associated with the nervous, metabolic, and auditory systems, which can be linked to unique traits in shrews. Notably, genes suggested to be under convergent evolution in echolocating mammals exhibited accelerated regions in shrews, and pathways linked to putative body size plasticity were detected. These findings provide insight into the evolutionary mechanisms shaping shrew species, shedding light on their adaptation and divergence over time.

Synthetic syntrophy for adenine nucleotide cross-feeding between metabolically active nanoreactors.

Living systems depend on continuous energy input for growth, replication and information processing. Cells use membrane proteins as nanomachines to convert light or chemical energy of nutrients into other forms of energy, such as ion gradients or adenosine triphosphate (ATP). However, engineering sustained fuel supply and metabolic energy conversion in synthetic systems is challenging. Here, inspired by endosymbionts that rely on the host cell for their nutrients, we introduce the concept of cross-feeding to exchange ATP and ADP between lipid-based compartments hundreds of nanometres in size. One population of vesicles enzymatically produces ATP in the mM concentration range and exports it. A second population of vesicles takes up this ATP to fuel internal reactions. The produced ADP feeds back to the first vesicles, and ATP-dependent reactions can be fuelled sustainably for up to at least 24 h. The vesicles are a platform technology to fuel ATP-dependent processes in a sustained fashion, with potential applications in synthetic cells and nanoreactors. Fundamentally, the vesicles enable studying non-equilibrium processes in an energy-controlled environment and promote the development and understanding of constructing life-like metabolic systems on the nanoscale.

Human Breast Milk Exosomes: Affecting Factors, Their Possible Health Outcomes, and Future Directions in Dietetics

Background: Human breast milk is a complex biological fluid containing multifaceted biological compounds that boost immune and metabolic system development that support the short- and long-term health of newborns. Recent literature suggests that human breast milk is a substantial source of nutrients, bioactive molecules, and exosomes. Objectives: This review examines the factors influencing exosomes noted in human milk and the impacts of exosomes on infant health. Furthermore, it discusses potential future prospects for exosome research in dietetics. Methods: Through a narrative review of the existing literature, we focused on exosomes in breast milk, exosome components and their potential impact on exosome health. Results: Exosomes are single-membrane extracellular vesicles of endosomal origin, with an approximate radius of 20–200 nm. They are natural messengers that cells secrete to transport a wide range of diverse cargoes, including deoxyribonucleic acid, ribonucleic acid, proteins, and lipids between various cells. Some studies have reported that the components noted in exosomes in human breast milk could be transferred to the infant and cause epigenetic changes. Thus, it can affect gene expression and cellular event regulation in several tissues. Conclusions: In this manner, exosomes are associated with several pathways, including the immune system, oxidative stress, and cell cycle, and they can affect the short- and long-term health of infants. However, there is still much to learn about the functions, effectiveness, and certain impacts on the health of human breast milk exosomes.

Effect of CAT gene polymorphism on sensitivity of human lymphocytes to genotoxic effect of organochlorine pesticide in vitro

Introduction. Over recent decades, toxicogenetic studies have focused on the issues of genome instability under the action of genotoxicants, taking into account biomarkers of sensitivity. The question about the genotoxic potential of chlorpyrifos remains open, since both positive and negative effects have been revealed in various tests. The aim of the study is the investigation of sensitivity of donor peripheral blood lymphocytes to chlorpyrifos in vitro and evaluation of the contribution of polymorphism of antioxidant defense system genes (CAT (rs1001179), SOD2 (rs4880)) to the response of human cells to the action of genotoxicant. Materials and methods. The DNA damaging effect of chlorpyrifos was assessed on lymphocytes from fifty two donors using DNA-comet assay with metabolic activation (+S9) and without it (–S9). The study of cytotoxic effects of chlorpyrifos on human lymphocytes was carried out using an automatic fluorescent cell analyzer ADAMII LS. Results. Chlorpyrifos had a pronounced cytotoxic effect on lymphocytes in most donors in the absence of metabolic activation system. With increasing concentration of the pesticide in the medium and time of cultivation, the viability of lymphocytes decreased, and the proportion of cells in late apoptosis and necrosis increased. Positive genotoxic effects were found on the cells of 33 donors (-S9). In the presence of the S9, mild but statistically significant effects were detected only on cells from 2 donors. % DNA values in the comet tail after exposure to the pesticide varied for cells from different donors. In the absence of metabolic activation, a statistically significant increase in the level of DNA damage was found in cells of individuals with genotype AA (homozygote for the minor allele) for the CAT G262A catalase gene (rs1001179), compared with homozygote for the dominant GG allele. Limitations. The genotoxicity of chlorpyryfos was studied in vitro. Conclusion. The results of the study shown cytotoxic and genotoxic effects of chlorpyrifos. The sensitivity of lymphocytes from different donors to the pesticide was found to be significantly different. The association of the level of DNA damage under exposure of chlorpyrifos in vitro with the G262A polymorphism of the catalase gene was found. The research also confirms the possibility of using a model test-system with peripheral blood lymphocytes to assess the potential genetic risk for humans and to study the contribution of gene polymorphism to individual sensitivity to the action of genotoxicants.

Gut Bacterial Metabolites from Tryptophan and Phenylalanine Induce Melatonin Synthesis and Extend Sleep Duration in Mice.

The human gut microbiota significantly influences various physiological systems, including immune, nervous, and metabolic systems. Recent studies suggest that gut microbiota may affect sleep quality with certain bacteria and metabolites being linked to sleep patterns. However, the underlying chemical signaling pathway remains unclear. In this study, we investigated the effect of four gut bacteria-derived metabolites, tryptamine (1), indolokine A5 (2), 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE, 3), and phenethylamine (PEA, 4), on sleep characteristics in mice and melatonin biosynthesis pathways in zebrafish. Their sleep-promoting effects were evaluated in a pentobarbital-induced sleep mouse model, revealing significant increases in sleep duration and blood melatonin levels, particularly with ITE (3) and PEA (4). Further tests in zebrafish embryos showed that ITE (3) and PEA (4) increased the expression of genes for melatonin biosynthesis (Aanat1, Aanat2, Tph1a, and Hiomt) in a concentration-dependent manner, indicating their potential as therapeutic agents for sleep disorders.

Interrelation of protein metabolism and autonomic nervous system in laying hens

The study of factors influencing the processes of protein metabolism in the poultry body will help to better balance the diet, which will help to more effectively stimulate the growth of animal productivity. The aim of the work was to investigate the role of the autonomic nervous system in protein metabolism and to take into account the individual characteristics of the poultry organism, characterized by different tone of the autonomic nervous system. The formation of experimental groups of animals was carried out by electrocardiographic examination using the Baevsky method, on the basis of which three experimental groups of animals were formed: normotonics, vagotonics, and sympathotonics. The blood serum was studied using a LabLine-010 spectrophotometer (Austria) and test systems from Laboratory Granum LLC, Kharkiv. Kharkiv. According to the results of the biochemical study, it was found that the content of total protein, which was compared with the experimental group of normotonics (46.10±1.35 g/l) with a balanced sympathovagal balance, was 14.8 % lower than that of the experimental group of sympathotonics (54.10±2.60 g/l) (P&lt;0.01) and 18.1 % lower than that of the experimental group of vagotonics (56.30±1.90 g/l) (P&lt;0.01). The albumin content, which was compared with the experimental group of normotonics (4.56±0.55 g/l) with a balanced sympathovagal balance, was 40.55 % lower than that of the experimental group of sympathotonics (6.96±0.49 g/l) (P&lt;0.001) and 1.5 times lower than that of the experimental group of vagotonics (7.67±0.38 g/l) (P&lt;0.01). The creatinine content compared to the normotonic group (47.12±0.77) with a balanced sympathovagal balance was lower than that of the experimental group by 6.77 % compared to the experimental group of vagotonic poultry (7.67±0.38 g/l) (P&lt;0.001). Taking into account the individual characteristics of the poultry organism and establishing the tone of the autonomic nervous system, it was determined that the autonomic nervous system has an effect on protein metabolism in poultry. The prospect of further research is to study the use of nanoaquahelate preparations to improve productivity and metabolic processes, taking into account the tone of the autonomic nervous system.