Over last years, the world’s aging populations are rising rapidly, and the phenotypes of cognitive insufficiency, such as old age, depression and dementia, are increasing. Search for approaches to discrimination between such phenotypes is extremely relevant. Current studies present compelling evidence of the key role of immune system (its peripheral compartment), and the stress response system in physiological brain health. Therefore, assessment of complex interactions between immune and neuroendocrine systems may be an effective way to differentiate between depression and early stages of dementia in elderly people. Our purpose was to reveal peripheral molecular messages, e.g., cytokines and stress hormones, in the context of cognitive impairment phenotypes: healthy old age/old age depression/dementia. Eighty elderly people were included into groups as follows: “Healthy ageing”, “Dementia”, “Depression”. Levels of certain cytokines: IL-6, IL-1β, TNFα, IFNγ, IL-10, and stress hormones (cortisol, ACTH, dopamine, noradrenaline, and adrenaline) were determined in blood plasma by ELISA. The intergroup differences were evaluated by the Kruskal-Wallis test with Conover-Inman post-hoc pairwise comparisons. For differential diagnostics between the groups of elderly people with varying grades of cognitive impairment, we used linear canonical discriminant analysis performed on the ranks. It has been shown that cognitive insufficiency phenotypes—old age depression and dementia—differ from the healthy ageing phenotype with their high peripheral levels of TNFα cytokine and low levels of IL-1β. The differences between depression in elderly and dementia included lower level of IL-10 in depression (lower than in “Healthy ageing”), and high IL-6 in dementia (compared to “Healthy ageing”). Evaluation of the hypothalamic-pituitary and sympatho-adreno-medullary axes hormones showed hyporesponsiveness of hypothalamic-pituitary axis, regardless of cognitive insufficiency phenotypes, along with activation of sympatho-adreno-medullary axis, i.e., high dopamine level in old age depression with dementia, and high adrenaline level in dementia, than in depression of elderly phenotype and healthy ageing. Such significant differences in the levels of molecular messages, i.e., cytokines and stress hormones among the old age person groups, enabled diagnostic efficacy of 87.5% to differentiate cognitive phenotypes of aging: healthy ageing, old age depression, and dementia.
Due to the steady increase in the number of children with autism and the high heterogeneity of clinical groups, the diagnosis of these disorders and their severity is an urgent problem in modern medicine. In the course of the work, 126 children from 3 to 13 years old with typical neurodevelopment and with severe and mild autism spectrum disorders (ASD) were examined. Disease severity was determined according to the Childhood Autism Rating Scale (CARS). The levels of pro-/anti-inflammatory cytokines and neurotrophic factors (nerve growth factor beta and brain-derived neurotrophic factor) in blood plasma were assessed by enzyme immunoassay. Associations between indicators in each group of patients were assessed using the Spearman test and visualized as a heatmap of correlations. Statistical data processing was carried out in the R software. Significantly high levels of IL-4 in blood plasma and a decrease in the number of significant correlations within/between systems were revealed in children with mild autism compared with children with typical neurodevelopment. Such data can probably reflect the theory that some children with ASD are characterized by slow brain development, as a variant of the evolutionary norm. On the contrary, in children with severe ASD, high systemic levels of IL-6 and IFNg are shown against the background of low values of IL-10, IL-1β, TNFα and NGFβ, supported by the almost complete absence of intra/ and intersystem interactions. This may act as an indicator of maladaptation of the immune and nervous systems in severe autism, which contributes to the pathogenesis of the disease. Thus, a set of indicators: high levels of key pro-inflammatory cytokines - IL-6 and IFNg, low levels of IL-10, NGFβ and disintegration of the cytokine and nervous systems in the periphery can be proposed as an approach to indicate the severity of the condition in children with ASD.
Chronic low-level inflammation during the aging process is a key risk factor for the activation of resident cells of the brain innate immune system of the (microglia and astrocytes). Such activation leads to the development of neuroinflammation and cognitive impairment which are typical to neurodegenerative diseases such as Alzheimers disease, vascular dementia, Parkinson disease etc. Currently, there is a lack of minimally invasive, affordable methods for diagnosing age-related neurodegenerative diseases and drugs that could slow down or prevent their progression. Hence, a search for new peripheral biomarkers is required, both for diagnostics and monitoring the efficiency of drug therapy. The option of using microRNAs as such biomarkers is under discussion. Our goal was to identify a leukocyte microRNA signature in vascular dementia as compared with healthy aging and reproductive age, in view of inflammation and cognitive deficits. We have examined 54 persons from young to senile age who were classified into the following groups: Vascular dementia, Healthy aging and Reproductive age. Expression of miRNAs known as regulators of communications between the immune and nervous systems (let-7d, let-7g, miR-21, miR-124, miR-146a, miR-155, miR-342-3p) was measured in peripheral blood leukocytes. The decision to study leukocytes was made, since these blood cells are responsible for immune functions, and, especially, cytokine production during aging. Total RNA was isolated by phenol-chloroform technique. The microRNA expression was determined by quantitative polymerase chain reaction with SYBRGreen. The U6 gene of small nuclear DNA was used as a reference housekeeping gene. The differences between groups were determined using the KruskalWallis test with post hoc pairwise comparisons according to ConoverInman. As a result of the study, it was found that the expression of microRNA-21 and microRNA-342 in leukocytes of elderly/senile people, both in healthy aging and in vascular dementia, was increased when compared to the persons in their reproductive age. In the persons with vascular dementia, the expression level of miRNA-124 and miRNA-342 in peripheral blood leukocytes was higher than in healthy aging group. Hence,, microRNA-124 and microRNA-342 may be informative biomarkers for the diagnostics of vascular dementia. However, large-scale studies of their biomarker potential are warranted.
Представлен анализ лекарственной формы «Эликсиры» в отечественной и зарубежных фармакопеях. Приведен перечень зарегистрированных в настоящий момент лекарственных препаратов отечественного и зарубежного производства в данной лекарственной форме. На основе анализа и обобщения информации, приведенной в нормативной документации отечественных и зарубежных производителей лекарственных препаратов, приведен перечень показателей качества, по которым необходимо стандартизовать лекарственные препараты в лекарственной форме «Эликсиры».
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