Background: Epilepsy is a group of disorders characterized by a cluster of clinical and EEG signs leading to the formation of abnormal synchronous excitation of neurons in the brain. It is one of the most common neurological disorders worldwide; and is characterized by aberrant expression patterns; both at the level of matrix transcripts and at the level of regulatory RNA sequences. Aberrant expression of a number of microRNAs can mark a particular epileptic syndrome; which will improve the quality of differential diagnosis. Materials and Methods: In this work; the expression profile of six microRNAs was analyzed: hsa-miR-106b-5p; hsa-miR-134-5p; hsa-miR-122-5p; hsa-miR-132-3p; hsa-miR-155-5p; and hsa-miR-206-5p in the blood plasma of patients suffering from temporal lobe epilepsy (n = 52) and juvenile myoclonic epilepsy (n = 42); n—amount of participants; in comparison with healthy volunteers. The expression analysis was carried out using RT-PCR. Mathematical processing of the data was carried out according to the Livak method. Results: A statistically significant change in the expression of hsa-miR-106b-5p; hsa-miR-134-5p; hsa-miR-122-5p; and hsa-miR-132-3p was found. An increase in the expression of hsa-miR-134-5p and hsa-miR-122-5p was registered in the group of patients with temporal lobe epilepsy compared to the control; as well as an increase in the expression of hsa-miR-132-3p and hsa-miR-106b-5p in the juvenile myoclonic epilepsy group compared to the control. hsa-miR-122-5p; 106b-5p; 132-3p are also able to discriminate groups with different syndromes. Additionally; a number of microRNAs are able to discriminate patients with drug-resistant and drug-sensitive forms of epilepsy from the control; as well as patients with hippocampal sclerosis and patients without hippocampal sclerosis from the control. Conclusion. Our data allow us to propose these microRNAs as plasma biomarkers of various epileptic syndromes

Epilepsy is a brain disorder characterized by a persistent predisposition to epileptic seizures. With various etiologies of epilepsy, a significant proportion of patients develop pharmacoresistance to antiepileptic drugs, which necessitates the search for new therapeutic methods, in particular, using gene therapy. This review discusses the use of adeno-associated viral (AAV) vectors in gene therapy for epilepsy, emphasizing their advantages, such as high efficiency of neuronal tissue transduction and low immunogenicity/cytotoxicity. AAV vectors provide the possibility of personalized therapy due to the diversity of serotypes and genomic constructs, which allows for increasing the specificity and effectiveness of treatment. Promising orientations include the modulation of the expression of neuropeptides, ion channels, transcription, and neurotrophic factors, as well as the use of antisense oligonucleotides to regulate seizure activity, which can reduce the severity of epileptic disorders. This review summarizes the current advances in the use of AAV vectors for the treatment of epilepsy of various etiologies, demonstrating the significant potential of AAV vectors for the development of personalized and more effective approaches to reducing seizure activity and improving patient prognosis.

Temporal lobe epilepsy has various origins, involving or not involving structural changes in brain tissue. The mechanisms of epileptogenesis are associated with cell regulation and signaling disruptions expressed in varied levels of proteins. The blood plasma proteomic profiling of temporal lobe epilepsy patients (including magnetic resonance imaging (MRI)-positive and MRI-negative ones) and healthy volunteers using mass spectrometry and label-free quantification revealed a list of differently expressed proteins. Several apolipoproteins (APOA1, APOD, and APOA4), serpin protease inhibitors (SERPINA3, SERPINF1, etc.), complement components (C9, C8, and C1R), and a total of 42 proteins were found to be significantly upregulated in the temporal lobe epilepsy group. A classification analysis of these proteins according to their biological functions, as well as a review of the published sources, disclosed the predominant involvement of the processes mostly affected during epilepsy such as neuroinflammation, intracellular signaling, lipid metabolism, and oxidative stress. The presence of several proteins related to the corresponding compensatory mechanisms has been noted. After further validation, the newly identified temporal lobe epilepsy biomarker candidates may be used as epilepsy diagnostic tools, in addition to other less specific methods such as electroencephalography or MRI.

Structural or post-traumatic epilepsy often develops after brain tissue damage caused by traumatic brain injury, stroke, infectious diseases of the brain, etc. Most often, between the initiating event and epilepsy, there is a period without seizures-a latent period. At this time, the process of restructuring of neural networks begins, leading to the formation of epileptiform activity, called epileptogenesis. The prediction of the development of the epileptogenic process is currently an urgent and difficult task. MicroRNAs are inexpensive and minimally invasive biomarkers of biological and pathological processes. The aim of this study is to evaluate the predictive ability of microRNAs to detect the risk of epileptogenesis. In this study, we conducted a systematic search on the MDPI, PubMed, ScienceDirect, and Web of Science platforms. We analyzed publications that studied the aberrant expression of circulating microRNAs in epilepsy, traumatic brain injury, and ischemic stroke in order to search for microRNAs-potential biomarkers for predicting epileptogenesis. Thus, 31 manuscripts examining biomarkers of epilepsy, 19 manuscripts examining biomarkers of traumatic brain injury, and 48 manuscripts examining biomarkers of ischemic stroke based on circulating miRNAs were analyzed. Three miRNAs were studied: miR-21, miR-181a, and miR-155. The findings showed that miR-21 and miR-155 are associated with cell proliferation and apoptosis, and miR-181a is associated with protein modifications. These miRNAs are not strictly specific, but they are involved in processes that may be indirectly associated with epileptogenesis. Also, these microRNAs may be of interest when they are studied in a cohort with each other and with other microRNAs. To further study the microRNA-based biomarkers of epileptogenesis, many factors must be taken into account: the time of sampling, the type of biological fluid, and other nuances. Currently, there is a need for more in-depth and prolonged studies of epileptogenesis.

Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. Tissue reorganization at the site of the epileptogenic focus is accompanied by changes in the expression patterns of protein molecules. The study of mRNA and its corresponding proteins is crucial for understanding the pathogenesis of the disease. Protein expression profiles do not always directly correlate with the levels of their transcripts; therefore, it is protein profiling that is no less important for understanding the molecular mechanisms and biological processes of TLE. The study and annotation of proteins that are statistically significantly different in patients with TLE is an approach to search for biomarkers of this disease, various stages of its development, as well as a method for searching for specific targets for the development of a further therapeutic strategy. When writing a systematic review, the following aggregators of scientific journals were used: MDPI, PubMed, ScienceDirect, Springer, and Web of Science. Scientific articles were searched using the following keywords: "proteomic", "mass-spectrometry", "protein expression", "temporal lobe epilepsy", and "biomarkers". Publications from 2003 to the present have been analyzed. Studies of brain tissues, experimental models of epilepsy, as well as biological fluids, were analyzed. For each of the groups, aberrantly expressed proteins found in various studies were isolated. Most of the studies omitted important characteristics of the studied patients, such as: duration of illness, type and response to therapy, gender, etc. Proteins that overlap across different tissue types and different studies have been highlighted: DPYSL, SYT1, STMN1, APOE, NME1, and others. The most common biological processes for them were the positive regulation of neurofibrillary tangle assembly, the regulation of amyloid fibril formation, lipoprotein catabolic process, the positive regulation of vesicle fusion, the positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway, removal of superoxide radicals, axon extension, and the regulation of actin filament depolymerization. MS-based proteomic profiling for a relevant study must accept a number of limitations, the most important of which is the need to compare different types of neurological and, in particular, epileptic disorders. Such a criterion could increase the specificity of the search work and, in the future, lead to the discovery of biomarkers for a particular disease.

Due to elevated frequency of autoimmune epilepsy cases, the issues related to reliable clinical and laboratory-instrumental criteria for establishing the disease etiology become relevant. Differentiated assessment of autoantibody markers allows to choose the most effective tactics for managing patients. The article presents the criteria for assessing autoimmune epilepsy as well as diagnostic scales, features related to clinical picture and response to therapy based on the type of synthesized autoantibodies. Therapeutic lines and targets for immunomodulatory and antiepileptic drugs used in autoimmune epilepsy are detailed, the knowledge of which along with clinical and laboratory data collectively allow to determine effective and safe therapy algorithm.

Mesial temporal lobe epilepsy is the most common type of epilepsy. For most patients suffering from TLE, the only treatment option is surgery. However, there is a high possibility of relapse. Invasive EEG as a method for predicting the outcome of surgical treatment is a very complex and invasive manipulation, so the search for outcome biomarkers is an urgent task. MicroRNAs as potential biomarkers of surgical outcome are the subject of this study. For this study, a systematic search for publications in databases such as PubMed, Springer, Web of Science, Scopus, ScienceDirect, and MDPI was carried out. The following keywords were used: temporal lobe epilepsy, microRNA, biomarkers, surgery, and outcome. Three microRNAs were studied as prognostic biomarkers of surgical outcome: miR-27a-3p, miR-328-3p, and miR-654-3p. According to the results of the study, only miR-654-3p showed a good ability to discriminate between patients with poor and good surgical outcomes. MiR-654-3p is involved in the following biological pathways: ATP-binding cassette drug transporters, glutamate transporter SLC7A11, and TP53. A specific target for miR-654-3p is GLRA2, the glycine receptor subunit. MicroRNAs, which are diagnostic biomarkers of TLE, and epileptogenesis, miR-134-5p, MiR-30a, miRs-143, etc., can be considered as potential biomarkers of surgical outcome, as they can be indicators of early and late relapses. These microRNAs are involved in the processes characteristic of epilepsy: oxidative stress and apoptosis. The study of miRNAs as potential predictive biomarkers of surgical outcome is an urgent task and should be continued. However, when studying miRNA expression profiles, it is important to take into account and note a number of factors, such as the type of sample under study, the time of sampling for the study, the type and duration of the disease, and the type of antiepileptic treatment. Without taking into account all these factors, it is impossible to assess the influence and involvement of miRNAs in epileptic processes.

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in adults. Experimental and clinical data indicate that neuroinflammation and neurodegeneration accompanying epileptogenesis make a significant contribution to the chronicity of epilepsy and the development of drug resistance in TLE cases. Changes in plasma and serum concentrations of proteins associated with neuroinflammation and neurodegeneration can be predictive biomarkers of the course of the disease. This study used an enzyme-linked immunosorbent assay of the following plasma proteins: brain-derived neurotrophic factor (BDNF), tumor necrosis factor alpha (TNFa), and high-mobility group protein B1 (HMGB1) in patients with mesial TLE to search for biomarkers of the disease. The objective of the study was to examine biomarkers of the neuroinflammation and neurodegeneration of plasma: BDNF, TNFa, and HMGB1. The aim of the study was to identify changes in the concentration of circulating pro-inflammatory and neurotrophic factors that are prognostically significant for the development of drug resistance and the course of TLE. A decrease in the concentration of BDNF, TNFa, and HMGB1 was registered in the group of patients with TLE compared with the control group. A significant decrease in the concentration of HMGB1 in patients with drug-resistant TLE was observed. Aberrations in plasma concentrations of BDNF, TNFa, and HMGB1 in patients with TLE compared with the controls have been confirmed by earlier studies. A decrease in the expression of the three biomarkers may be the result of neurodegenerative processes caused by the long course of the disease. The results of the study may indicate the acceptability of using HMGB1 and TNFa as prognostic biological markers to indicate the severity of the disease course and the risk of developing drug resistance.

Our study aimed to develop a comprehensive approach to the management of patients with involutional skin changes, considering the predictors of premature skin aging. The study included two stages, whereby 78 women with no history of aesthetic procedures that could have affected their perceived age were examined. In the first stage, we examined factors associated with premature skin aging. In the second stage, a blind, comparative placebo-controlled study of the effectiveness of intradermal injections for the treatment of involutional skin changes was conducted. Parameters reflecting skin aging were identified. The sum of these parameters could be used to diagnose premature skin aging in patients with no history of aesthetic treatment. For other patients, we developed indicators that can be applied to determine whether there is a risk of premature skin aging. Patients with premature aging have an increased risk of adverse events, such as impaired regeneration and wound healing, postprocedural hematomas, etc. For the correction of involutional skin changes in patients with premature aging, the collagen product (Collost) had the greatest clinical efficiency and the greatest patient satisfaction. A complex product based on HA (Teosyal Redensity 1) had comparable efficiency, with slightly less patient satisfaction. The product based on native HA (Hyon 1.8%) had low efficiency in the group of patients with premature aging and high efficiency in the group of patients with normal aging.

BackgroundAssessing the role of oxytocin (OT) in the regulation of social interaction is a promising area that opens up new opportunities for studying the mechanisms of developing autism spectrum disorders (ASD).AimTo assess the correlation between the salivary OT level and age-related and psychopathological symptoms of children with intellectual disability (ID) and ASD.MethodsWe used the clinical and psychopathological method to assess the signs of ASD based on International Classification of Diseases (ICD-10), the severity of ASD was specified by the selected Russian type version “Childhood Autism Rating Scale” (CARS). Patients of both groups had an IQ score below 70 points.ResultsThe median and interquartile range of salivary OT levels in patients with ID and ASD were 23.897 [14.260–59.643] pg/mL, and in the group ID without ASD - Me = 50.896 [33.502–83.774] pg/mL (p = 0.001). The severity of ASD on the CARS scale Me = 51.5 [40.75–56.0] score in the group ID with ASD, and in the group ID without ASD—at the level of Me = 32 [27.0–38.0] points (p < 0.001). According to the results of correlation-regression analysis in the main group, a direct correlation was established between salivary OT level and a high degree of severity of ASD Rho = 0.435 (p = 0.005). There was no correlation between the salivary OT level and intellectual development in the group ID with ASD, Rho = 0.013 (p = 0.941) and we have found a relationship between oxytocin and intellectual development in the group ID without ASD, Rho = 0.297 (p = 0.005). There was no correlation between salivary OT and age, ASD and age.ConclusionThe results of this study indicate that patients in the group ID with ASD demonstrated a lower level of salivary OT concentration and a direct relationship between the maximum values of this indicator and the severity of autistic disorders, in contrast to patients in the group ID without ASD.