Nervous System Regulation Research Articles

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).

MMiKG: a knowledge graph-based platform for path mining of microbiota-mental diseases interactions.

The microbiota-gut-brain axis denotes a two-way system of interactions between the gut and the brain, comprising three key components: (1) gut microbiota, (2) intermediates and (3) mental ailments. These constituents communicate with one another to induce changes in the host's mood, cognition and demeanor. Knowledge concerning the regulation of the host central nervous system by gut microbiota is fragmented and mostly confined to disorganized or semi-structured unrestricted texts. Such a format hinders the exploration and comprehension of unknown territories or the further advancement of artificial intelligence systems. Hence, we collated crucial information by scrutinizing an extensive body of literature, amalgamated the extant knowledge of the microbiota-gut-brain axis and depicted it in the form of a knowledge graph named MMiKG, which can be visualized on the GraphXR platform and the Neo4j database, correspondingly. By merging various associated resources and deducing prospective connections between gut microbiota and the central nervous system through MMiKG, users can acquire a more comprehensive perception of the pathogenesis of mental disorders and generate novel insights for advancing therapeutic measures. As a free and open-source platform, MMiKG can be accessed at http://yangbiolab.cn:8501/ with no login requirement.

Autonomic nervous system and postural control regulation during orthostatic test as putative markers of physical resilience among community-dwelling older adults

IntroductionWe examined whether autonomic nervous system (ANS) and postural control regulation during orthostatic test reflect physical resilience by studying their associations with maximal walking speed and mortality. MethodsThe participants were community-dwelling Finnish men (n = 303) and women (n = 386) aged 75, 80, and 85 years at baseline. Systolic and diastolic blood pressure (BP), heart rate, heart rate variability (HRV), respiratory rate, and postural sway were obtained using a digital sphygmomanometer, a single-channel ECG, and thigh- and chest-worn accelerometers. Linear and Cox regression models were used to estimate the associations of the physiological indices with maximal 10-m walking speed and 5-year mortality separately for sexes. ResultsBetter maintenance of BP under orthostatic stress was associated with faster walking speed in women and lower mortality hazard in men. Greater HRV in terms of low frequency power and lower respiration rate in supine position and smaller orthostatic changes in these were associated with faster walking speed especially in women. Less postural sway after standing up was associated with faster walking speed in women (−0.057, SE 0.022, p = 0.011) and more postural sway with increased mortality hazard in men (HR 1.71, 95 % CI 1.20–2.43) even after controlling for BP responses. ConclusionsIn addition to ANS regulation at rest and under stress, adaptation of postural control system to orthostasis may be used in quantifying older adults' physical resilience. Wearable sensors capturing stimulus-response patterns and natural fluctuations of body functions may provide opportunities to monitor and incorporate different subsystems' resilience also in free-living conditions.

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.

Treatment of hypothalamic obesity in people with hypothalamic injury: new drugs are on the horizon.

Hypothalamic obesity (HO) is a complex and rare disorder affecting multiple regulatory pathways of energy intake and expenditure in the brain as well as the regulation of the autonomic nervous system and peripheral hormonal signaling. It can be related to monogenic obesity syndromes which often affect the central leptin-melanocortin pathways or due to injury of the hypothalamus from pituitary and hypothalamic tumors, such as craniopharyngioma, surgery, trauma, or radiation to the hypothalamus. Traditional treatments of obesity, such as lifestyle intervention and specific diets, are still a therapeutic cornerstone, but often fail to result in meaningful and sustained reduction of body mass index. This review will give an update on pharmacotherapies of HO related to hypothalamic injury. Recent obesity drug developments are promising for successful obesity intervention outcomes.

Mechanisms underlying probiotic effects on neurotransmission and stress resilience in fish via transcriptomic profiling

In recent years, studies have highlighted the significant impact of probiotic treatment on the central nervous system (brain) and stress regulation through the microbiota-gut-brain axis, yet there have been limited knowledge on this axis in fish. Therefore, this study aimed to enhance the current understanding of the mechanisms underlying probiotic effects on neurotransmission and stress alleviation in fish through transcriptomic profiling. In this study, olive flounders (Paralichthys olivaceus) were subjected to two trial setups: a 1-month lab-scale trial and a 6-month field-scale trial, with and without the probiotic strain Lactococcus lactis WFLU12. RNA-Seq analysis was performed using liver samples collected from fish at one-month post-feeding (mpf) in both trials. Additionally, fish growth was monitored monthly, and serological parameters were measured at one mpf in the field-scale experiment. The results of the lab-scale trial showed that probiotic administration significantly upregulated genes related to neurotransmission, such as htr3a, mao, ddc, ntsr1, and gfra2. These findings highlight the impact of probiotics on modulating neurotransmission via the microbiota-gut-brain axis. In the field-scale experiment, fish growth was significantly promoted and the sera levels of AST, LDH, and cortisol were significantly higher in the control group compared to the probiotics group. Furthermore, genes involved in stress responses (e.g. hsp70, hsp90B1, hspE1, prdx1, and gss) and transcriptional regulators (e.g. fos, dusp1, and dusp2) exhibited significant upregulation in the control group compared to the probiotics group, indicating that probiotic administration can alleviate stress levels in fish. Overall, this study provides valuable insights into the mechanisms underlying the beneficial effects of probiotics in fish, specifically regarding their impact on neurotransmission and stress alleviation.

The choroidal nervous system: a link between mineralocorticoid receptor and pachychoroid.

Central serous chorioretinopathy (CSCR) belongs to the pachychoroid spectrum, a pathological phenotype of the choroidal vasculature, in which blood flow is under the choroidal nervous system (ChNS) regulation. The pathogenesis of CSCR is multifactorial, with the most recognised risk factor being intake of glucocorticoids, which activate both the gluco- and the mineralocorticoid (MR) receptors. As MR over-activation is pathogenic in the retina and choroid, it could mediate the pathogenic effects of glucocorticoids in CSCR. But the role of MR signalling in pachychoroid is unknown and whether it affects the ChNS has not been explored. Using anatomo-neurochemical characterisation of the ChNS in rodents and humans, we discovered that beside innervation of arteries, choroidal veins and choriocapillaris are also innervated, suggesting that the entire choroidal vasculature is under neural control. The numerous synapses together with calcitonin gene-related peptide (CGRP) vesicles juxtaposed to choroidal macrophages indicate a neuro-immune crosstalk. Using ultrastructural approaches, we show that transgenic mice overexpressing human MR, display a pachychoroid-like phenotype, with signs of choroidal neuropathy including myelin abnormalities, accumulation and enlargement of mitochondria and nerves vacuolization. Transcriptomic analysis of the RPE/choroid complex in the transgenic mice reveals regulation of corticoids target genes, known to intervene in nerve pathophysiology, such as Lcn2, rdas1/dexras1, S100a8 and S100a9, rabphilin 3a (Rph3a), secretogranin (Scg2) and Kinesin Family Member 5A (Kif5a). Genes belonging to pathways related to vasculature development, hypoxia, epithelial cell apoptosis, epithelial mesenchymal transition, and inflammation, support the pachychoroid phenotype and highlight downstream molecular targets. Hypotheses on the imaging phenotype of pachychoroid in humans are put forward in the light of these new data. Our results provide evidence that MR overactivation causes a choroidal neuropathy that could explain the pachychoroid phenotype found in transgenic mice overexpressing human MR. In patients with pachychoroid and CSCR in which systemic dysautonomia has been demonstrated, MR-induced choroidal neuropathy could be the missing link between corticoids and pachychoroid.

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.

Interaction of Orexin and Bone Morphogenetic Proteins in Steroidogenesis by Human Adrenocortical Cells.

Orexins are neuropeptides that play important roles in sleep-wake regulation and food intake in the central nervous system, but their receptors are also expressed in peripheral tissues, including the endocrine system. In the present study, we investigated the functions of orexin in adrenal steroidogenesis using human adrenocortical H295R cells by focusing on its interaction with adrenocortical bone morphogenetic proteins (BMPs) that induce adrenocortical steroidogenesis. Treatment with orexin A increased the mRNA levels of steroidogenic enzymes including StAR, CYP11B2, CYP17, and HSD3B1, and these effects of orexin A were further enhanced in the presence of forskolin. Interestingly, orexin A treatment suppressed the BMP-receptor signaling detected by Smad1/5/9 phosphorylation and Id-1 expression through upregulation of inhibitory Smad7. Orexin A also suppressed endogenous BMP-6 expression but increased the expression of the type-II receptor of ActRII in H295R cells. Moreover, treatment with BMP-6 downregulated the mRNA level of OX1R, but not that of OX2R, expressed in H295R cells. In conclusion, the results indicate that both orexin and BMP-6 accelerate adrenocortical steroidogenesis in human adrenocortical cells; both pathways mutually inhibit each other, thereby leading to a fine-tuning of adrenocortical steroidogenesis.

The Effect of Dexamethasone on Lipopolysaccharide-induced Inflammation of Endothelial Cells of the Blood-brain Barrier/Brain Capillaries.

A protective and regulatory barrier between the blood and the brain is constituted by the blood-brain barrier (BBB), which comprises microvascular endothelial cells providing homeostatic regulation of the central nervous system (CNS). Inflammation compromises the BBB and contributes to many CNS disorders. Anti-inflammatory effects are exerted by glucocorticoids (GCs) on a variety of cells. These GCs include dexamethasone (Dex), which is used for the treatment of inflammatory diseases and recently for the treatment of COVID-19. The purpose of this study was to determine whether low or high concentrations of Dex can attenuate the inflammatory response induced by lipopolysaccharide (LPS) in the in vitro BBB model. Brain endothelial cells (bEnd.5) were cultured and exposed to LPS (100ng/ml) and subsequently co-treated with Dex to investigate whether selected concentrations of Dex (0.1, 5, 10, 20μM) can modulate the inflammatory effects of LPS on bEnd.5 cells. Cell viability, cell toxicity, and cell proliferation were investigated, as well as the monitoring of membrane permeability (Trans Endothelial Electrical Resistance-TEER), and Enzyme-Linked Immune Assay (ELISA) kits were used to identify and quantify the presence of inflammatory cytokines (TNF-α and IL-1β). Dex, at a lower dosage (0.1μM, but not higher doses), was able to attenuate the inflammatory effects of LPS on bEnd.5 cells. Lower doses of Dex (0.1μM) had no detrimental effects on bEnd.5 cells, while higher Dex doses (5-20μM) decreased bEnd.5 viability, increased bEnd.5 cell toxicity, increased bEnd.5 cell monolayer permeability, and increased proinflammatory cytokine secretion. These results indicate that treatment of brain vascular inflammation with low doses of Dex should be advocated, while higher doses promote vascular inflammation.

Mindfulness-Based Intervention Effect on the Psychophysiological Marker of Self-Regulation in Women With Endometriosis-Related Chronic Pain

Endometriosis is a gynecological disease that involves a broad biopsychosocial compromise with the potential to create a negative vicious cycle. Despite the complexity of factors influencing women's improvement, most interventions investigated target just the peripheral nociceptive sources of endometriosis-related pain. An alternative is intervening in self-regulation, which can potentially influence multiple domains of the illness experience. The present study examines the effect of a brief Mindfulness-Based Intervention (bMBI) on attention and autonomic nervous system regulation in women with endometriosis-related pain. Also, explore the interaction between these self-regulation domains and the affective pain dimension. An exploratory analysis of the secondary outcomes of a pilot randomized controlled trial was performed. The vagally-mediated Heart Rate Variability (vmHRV) at rest, cognitive stress, and recovery was employed to measure autonomic regulation. The Flanker and Stroop tasks were used to estimate the attention domains. Results showed that bMBI (n = 26) significantly improved Flanker accuracy and Flanker and Stroop reaction time compared to the control group (n = 28). bMBI significantly increased vmHRV at rest and recovery after cognitive stress. Attention mediated the bMBI effect on affective pain improvement. Results suggest that bMBI improves self-regulation domains with the potential to develop a broad biopsychosocial benefit in the endometriosis context. PerspectiveThis article demonstrates the positive impact of a brief Mindfulness-Based Intervention on attention and parasympathetic regulation in women suffering from endometriosis-related pain. This mindfulness-induced self-regulation improvement can benefit affective pain and potentially multiple psychophysiological processes relevant to endometriosis.

Synthesis and anti-cancer potential of potent peripheral MAOA inhibitors designed to limit blood:brain penetration

Monoamine oxidases (MAOA/MAOB) are enzymes known for their role in neurotransmitter regulation in the central nervous system (CNS). Irreversible and non-selective MAO inhibitors (MAOi’s) were the first class of antidepressants, thus subsequent work on drugs such as the selective MAOA inhibitor clorgyline has focussed on selectivity and increased CNS penetration. MAOA is highly expressed in high grade and metastatic prostate cancer with a proposed effect on prostate cancer growth, recurrence, and drug resistance. A Phase II Clinical Trial has demonstrated the therapeutic effects of the irreversible nonselective MAOi phenelzine for prostate cancer. However, neurologic adverse effects led to early withdrawal in 25% of the enrolled patient-population. In this work, we revised the clorgyline scaffold with the goal of decreasing CNS penetration to minimize CNS-related side effects while retaining or enhancing MAOA inhibition potency and selectivity. Using the known co-crystal structure of clorgyline bound with FAD co-factor in the hMAOA active site as a reference, we designed and synthesized a series of compounds predicted to have lower CNS penetration (logBB). All synthesized derivatives displayed favorable drug-like characteristics such as predicted Caco-2 permeability and human oral absorption, and exhibited highly selective hMAOA binding interactions. Introduction of an HBD group (NH2 or OH) at position 5 of the phenyl ring clorgyline resulted in 3x more potent hMAOA inhibition with equivalent or better hMAOB selectivity, and similar prostate cancer cell cytotoxicity. In contrast, introduction of larger substituents at this position or at the terminal amine significantly reduced the hMAOA inhibition potency, attributed in part to a steric clash within the binding pocket of the MAOA active site. Replacement of the N-methyl group by a more polar, but larger 2-hydroxyethyl group did not enhance potency. However, introduction of a polar 2-hydroxy in the propyl chain retained the highly selective MAOA inhibition and cancer cell cytotoxicity of clorgyline while reducing its CNS score from 2 to 0. We believe that these results identify a new class of peripherally directed MAOIs that may allow safer therapeutic targeting of MAOA for a variety of anti-cancer and anti-inflammatory indications.

Human Breast Milk microRNAs, Potential Players in the Regulation of Nervous System.

Human milk is the biological fluid with the highest exosome amount and is rich in microRNAs (miRNAs). These are key regulators of gene expression networks in both normal physiologic and disease contexts, miRNAs can influence many biological processes and have also shown promise as biomarkers for disease. One of the key aspects in the regeneration of the nervous system is that there are practically no molecules that can be used as potential drugs. In the first weeks of lactation, we know that human breast milk must contain the mechanisms to transmit molecular and biological information for brain development. For this reason, our objective is to identify new modulators of the nervous system that can be used to investigate neurodevelopmental functions based on miRNAs. To do this, we collected human breast milk samples according to the time of delivery and milk states: mature milk and colostrum at term; moderate and very preterm mature milk and colostrum; and late preterm mature milk. We extracted exosomes and miRNAs and realized the miRNA functional assays and target prediction. Our results demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function. We found 132 different miRNAs were identified across all samples. Sixty-nine miRNAs had significant differential expression after paired group comparison. These miRNAs are implicated in gene regulation of dopaminergic/glutamatergic synapses and neurotransmitter secretion and are related to the biological process that regulates neuron projection morphogenesis and synaptic vesicle transport. We observed differences according to the delivery time and with less clarity according to the milk type. Our data demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function.

Unraveling the mystery of Takutsubo cardiomyopathy: a descendant of COVID-19 heart syndrome

Takutsubo, or stress cardiomyopathy (TCM) is one of the important cardiovascular disorders encountered during the COVID-19 pandemic. We performed a PubMed search of relevant articles and presented this review which included epidemiology, etiopathogenesis, diagnosis and treatment of this clinical disorder. Takutsubo is usually more common in women than men. COVID-19 infection or vaccination can incite severe emotional disorders such as anxiety and depression, which flames up impaired neural networks in the limbic system. This stirs up disorganized regulation of autonomic nervous system with predominance and excessive firing of sympathetic nervous system to the ventricular myocardium. Moreover, direct invasion and systemic effects of COVID-19 infection including hormonal influences, autoimmunity, cytokine storm and neighboring infections might also play a significant role in the manifestation of this disorder. It commonly presents signs and symptoms of left ventricular dysfunction. Although most cases are undergoing remission within a few weeks, complications such as LV outflow tract obstruction, thromboembolism and arrhythmias were also reported. Since clinical symptoms are non-specific, a high degree of clinical suspicion is warranted particularly with the co-existing COVID-19 infections. Clinicians often leaned upon battery of tests including ECG, echocardiography and CMR to rule out myocarditis and coronary artery disease. Supportive management including treatment of heart failure and any associated arrhythmias and thromboembolism. Recurrences are common, but the treatment of underlying psychiatric disorders, including relaxation techniques, is the key strategy to avoid future occurrences.

Expert consensus on the prevention and treatment of heatstroke in children (2023)

Due to the immature development of temperature regulation in the central nervous system, children have a weakened ability to regulate heat and are susceptible to heatstroke, which can lead to organ damage. Based on the evidence evaluation criteria of the Oxford Centre for Evidence-Based Medicine, this expert consensus group evaluated the current evidence on heatstroke in children, and formed this consensus through thorough discussion with the aim of providing reference for the prevention and treatment of heatstroke in children. This consensus includes classifications, pathogenesis, prevention measures, as well as pre-hospital and in-hospital treatment plans for heatstroke in children.

Regulation of enteric nervous system via sacral nerve stimulation in opioid-induced constipated rats.

Sacral nerve stimulation (SNS) has been employed for treating constipation. However, its mechanisms involving enteric nervous system (ENS) and motility are largely unknown. In this study, we investigated the possible ENS involvement of SNS in treating Loperamide-induced constipation in rats. Experiment-1 was designed to study the effects of acute SNS on whole colon transit time (CTT). In experiment-2, we induced constipation by Loperamide and then applied daily SNS or sham-SNS for 1 week. Choline acetyltransferase (ChAT), nitric oxide synthase (nNOS), and PGP9.5 in colon tissue were examined at the end of the study. Moreover, survival factors such as phosphorylated AKT (p-AKT) and Glial cell-derived neurotrophic factor (GDNF) were measures by immunohistochemistry (IHC) and western blot (WB). (1) SNS with one set of parameters shortened CTT starting at 90 min after phenol red administration (p < 0.05). (2) While Loperamide induced slow transit constipation with a significant reduction in fecal pellet number and feces wet weight, daily SNS for a week resolved constipation. (3) Moreover, SNS was able to shorten whole gut transit time comparing to sham-SNS (p = 0.01). (4) Loperamide reduced the number of PGP9.5 and ChAT positive cells, and downregulated ChAT protein expression and upregulated nNOS protein expression, whereas these detrimental effects were significantly reversed by SNS. (5) Furthermore, SNS increased expressions of both GDNF and p-AKT in colon tissue. (6) Vagal activity was reduced following Loperamide (p < 0.01); yet SNS normalized vagal activity. SNS with appropriate parameters improves opioid-induced constipation and reversed the detrimental effects of Loperamide on enteric neurons possibly via the GDNF-PI3K/Akt pathway.GRAPHICAL ABSTRACT.

Gene co-expression network and differential expression analyses of subcutaneous white adipose tissue reveal novel insights into the pathological mechanisms underlying ketosis in dairy cows

Ketosis is a common nutritional metabolic disease during the perinatal period in dairy cows. Although various risk factors have been identified, the molecular mechanism underlying ketosis remains elusive. In this study, subcutaneous white adipose tissue (sWAT) was biopsied for transcriptome sequencing on 10 Holstein cows with type II ketosis [blood β-hydroxybutyric acid (BHB) >1.4 mmol/L; Ket group] and another 10 cows without type II ketosis (BHB ≤1.4 mmol/L; Nket group) at d 10 after calving. Serum concentrations of nonesterified fatty acids (NEFA) and BHB, as indicators of excessive fat mobilization and circulating ketone bodies, respectively, were significantly higher in the Ket group than in the Nket group. Aspartate transaminase (AST) and total bilirubin (TBIL), as indicators of liver damage, were higher in the Ket group than in the Nket group. Weighted gene co-expression network analysis (WGCNA) of the sWAT transcriptome revealed modules significantly correlated with serum BHB, NEFA, AST, TBIL, and total cholesterol. The genes in these modules were enriched in the regulation of the lipid biosynthesis process. Neurotrophic tyrosine kinase receptor type 2 (NTRK2) was identified as the key hub gene by intramodular connectivity, gene significance, and module membership. Quantitative reverse transcription PCR analyses for these samples, as well as a set of independent samples, validated the downregulation of NTRK2 expression in the sWAT of dairy cows with type II ketosis. NTRK2 encodes tyrosine protein kinase receptor B (TrkB), which is a high-affinity receptor for brain-derived neurotrophic factor, suggesting that abnormal lipid mobilization in cows with type II ketosis might be associated with impaired central nervous system regulation of adipose tissue metabolism, providing a novel insight into the pathogenesis underlying type II ketosis in dairy cows.

Вплив об’ємного пневмопресингу низької інтенсивності в осіб з різним типом регуляції автономної нервової системи на центральну гемодинаміку

The purpose of our study was to determine changes in central hemodynamics under the condition of exposure to low-intensity IPC on the lower limbs in individuals with different types of regulation of the autonomic nervous system. The group of 62 participants in age of 18-22 years were investigated. Testing session that included pressure of 40 mmHg and 20-minute period of temporary occlusion of the lower extremities was performed by intermittent pneumatic compression with Recovery Pump PRX device (“Mego Aftek AC Ltd”, Israel). Before, during the exposure and recovery period of the procedure arterial blood pressure was recorded with Korotkov’s auscultative method by mercury tonometer (“Dr.Frei”A-10, Switzerland). For monitoring hemodynamic changes impedance cardiography (ICG) method was applied (“ХАІ-medica”, Kharkiv, Ukraine), by 15 sec. Based on the spectrum power values in the range of 0.15-0.4 (HFnorm), which was calculated according to the formula HFnorm = HF/(HF+LF)∙100%, 3 groups of volunteers were determined by method of sigma deviations. The 1st group included 29 people with a predominance of the sympathetic link of regulation of the autonomic nervous system, HF norm at rest is less than 40 nu. The 2nd - 19 people with a normotonic type of regulation, HFnorm from 40 to 60 nu. The 3rd - 14 people with a predominance of the parasympathetic link, HF norms higher than 60 nu. It has been established that in persons of the 1st group blood pressure maintenance is a result of complex neurohumoral interactions, in the 3rd group - due to vascular components. The decrease in the heart rate and cardiac index in the 1st and 2nd groups is caused by a decrease in venous return to the heart, and in the 3rd group - by contractile function of the heart. The proven impact of non-invasive IPC on peripheral blood circulation improving supports the concept of orthostatic tolerance. Future long-term studies are needed to evaluate the further long-term efficacy of IPC, safety and tolerability of this approach in clinical practice.

Cardiac Rhythms and Variation in Hibernating Arctic Ground Squirrels.

AbstractThe dramatic decrease in heart rate (HR) during entrance into hibernation is not a mere response to the lowering of core body temperature (Tb) but a highly regulated fall, as the decrease in HR precedes the drop in Tb. This regulated fall in HR is thought to be mediated by increased cardiac parasympathetic activity. Conversely, the sympathetic nervous system is thought to drive the increase of HR during arousal. Despite this general understanding, we lack temporal information on cardiac parasympathetic regulation throughout a complete hibernation bout. The goal of this study was to fill this gap in knowledge by using Arctic ground squirrels implanted with electrocardiogram/temperature telemetry transmitters. Short-term HR variability (root mean square of successive differences [RMSSD]), an indirect measure of cardiac parasympathetic regulation, was calculated in 11 Arctic ground squirrels. RMSSD, normalized as RMSSD/RR interval (RRI), increased fourfold during early entrance (from to , ). RMSSD/RRI peaked after HR dropped by over 90% and Tb fell by 70%. Late entrance was delineated by a decline in RMSSD/RRI while Tb continued to decrease. During arousal, HR started to increase 2 h before Tb, with a concurrent decrease in RMSSD/RRI to a new minimum. As Tb increased to a maximum during interbout arousal, HR declined, and RMSSD/RRI increased. These data suggest that activation of the parasympathetic nervous system initiates and regulates the HR decrease during entrance into hibernation and that withdrawal of parasympathetic activation initiates arousal. We conclude that cardiac parasympathetic regulation persists throughout all phases of a hibernation bout-a feature of the autonomic nervous system's regulation of hibernation that was not appreciated previously.

Gut microbiota and cardiac arrhythmia.

One of the most prevalent cardiac diseases is cardiac arrhythmia, however the underlying causes are not entirely understood. There is a lot of proof that gut microbiota (GM) and its metabolites have a significant impact on cardiovascular health. In recent decades, intricate impacts of GM on cardiac arrythmia have been identified as prospective approaches for its prevention, development, treatment, and prognosis. In this review, we discuss about how GM and its metabolites might impact cardiac arrhythmia through a variety of mechanisms. We proposed to explore the relationship between the metabolites produced by GM dysbiosis including short-chain fatty acids(SCFA), Indoxyl sulfate(IS), trimethylamine N-oxide(TMAO), lipopolysaccharides(LPS), phenylacetylglutamine(PAGln), bile acids(BA), and the currently recognized mechanisms of cardiac arrhythmias including structural remodeling, electrophysiological remodeling, abnormal nervous system regulation and other disease associated with cardiac arrythmia, detailing the processes involving immune regulation, inflammation, and different types of programmed cell death etc., which presents a key aspect of the microbial-host cross-talk. In addition, how GM and its metabolites differ and change in atrial arrhythmias and ventricular arrhythmias populations compared with healthy people are also summarized. Then we introduced potential therapeutic strategies including probiotics and prebiotics, fecal microbiota transplantation (FMT) and immunomodulator etc. In conclusion, the GM has a significant impact on cardiac arrhythmia through a variety of mechanisms, offering a wide range of possible treatment options. The discovery of therapeutic interventions that reduce the risk of cardiac arrhythmia by altering GM and metabolites is a real challenge that lies ahead.