Diabetes mellitus (DM) is associated with systemic inflammation and neuroinflammation, but the role of β-arrestin 2 in these processes remains poorly understood. The experimental study aimed to assess the effect of β-arrestin 2 deficiency on the pro-inflammatory state of mice with streptozotocin-induced diabetes. Male C57BL/6J mice and mice with the global β-arrestin 2 gene knockout (Arrb2-/-) were divided into four groups: non-diabetic wild type mice (WT, n = 8), diabetic wild-type mice (WTd, n = 8), non-diabetic knockout mice (KO, n = 8) and diabetic knockout mice (KOd, n = 9). Arrb2 knockout delayed the development of hyperglycemia: on day 39, blood glucose levels were significantly higher in WTd mice than in KOd mice (22.3 ± 8.09 vs. 14.37 ± 7.65 mmol/L, p < 0.05). Arrb2-/- mice also showed increased systemic inflammatory markers: the baseline percentage of neutrophils in KO mice was 2.6-fold higher than in WT mice (p < 0.0001). Starting from day 18 KOd mice had significantly higher neutrophil counts compared to KO and WTd (p < 0.05). β-Arrestin 2 deficiency was associated with increased mRNA expression of the genes encoding pro-inflammatory cytokines and protease-activated receptors. The most pronounced changes included a significant increased Il6 mRNA expression in the hippocampus of KO compared to WT (2.9-fold, p < 0.01), increased Tnf expression in the cerebral cortex (4.3-fold for KO/WT and 2.0-fold for KOd/WTd) and the hippocampus (3.2- and 2.3-fold, respectively) of Arrb2-/- animals compared to appropriate wild type groups (p < 0.05), as well as the increased Par1 and Par4 expression in the cerebral cortex and hippocampus of Arrb2-/- mice (2.4–7.3-fold, p < 0.01). These findings suggest that β-arrestin 2 deficiency is associated with a pro-inflammatory phenotype in the CNS and may contribute to inflammation dysregulation in DM.
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Lyme borreliosis (LB) is a naturally occurring transmissible disease caused by Borrelia burgdorferi sensu lato. Some patients develop LB after effective treatment of the acute stage of the disease with antibiotics, which may suggest involvement of chemokines and cytokines in its pathogenesis. This study aimed to assess serum levels of chemokine (C–C motif) ligand 19 (CCL19) and interleukin-23 (IL-23) in patients with post-Lyme syndrome (PLS) and neurological involvement, and to examine their association with clinical manifestations and laboratory parameters. We examined 70 individuals (26 [37.1%] male and 44 [62.9%] female) with confirmed LB who presented with neurological symptoms persisting or recurring within 6 months following the recommended antibiotic treatment. The serum levels of CCL19 and IL-23 were determined using a solid-phase enzyme immunoassay; CCL19 was high in 12 (17.1%) participants, and IL-23 in 10 (14.3%). Significant positive correlations were established between the concentrations of CCL19 and IL-23 (r = 0.65, p < 0.0001) and their hyperproduction (r = 0.79, p < 0.0001). The likelihood of developing Lyme disease after treatment increased significantly in association with overproduction of CCL19 and, especially, IL-23: odds ratio — 5.00; 95% CI: 1.00–24.84, p = 0.04, and 22.42; 95% CI: 1.25–399.93, p = 0.03, respectively. No correlation was found between the concentration of CCL19, IL-23, and the levels CRP, IgM and IgG antibodies to B. burgdorferi, ass well as IgG antibodies to SARS-CoV-2. A subject matter being discussed in the paper is how CCL19, IL-23 and other mechanisms participate in post-treatment pathogenesis of Lyme disease with neurological damage.
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Despite the successful practice of using the Russian-made original peptide complex (OPC), the complex pharmacodynamics is poorly understood. The study aimed to assess the effect of taking OPC on the prostate tissue oxygen consumption rate (OCR) in white outbred rats. The experiments involved 65 adult male white outbred rats (age 6 months, body weight 410.8 ± 2.7 g). The rats were kept under standard vivarium condition, each in a separate cage; the diet and drinking regime were standard. The difference in animal housing was that animals of the experimental group (n = 49) received OPC throughout 20 days before the day of the experiment: every day 0.35 mg (0.85 mg/kg) of the drug were dissolved in 20 mL of the drinking water the animals drank from the trough. The drug was not administered to the control group (n = 16). A prostatectomy was performed. The prostate tissue OCR was measured using the DKTP-03 optical dissolved oxygen sensor with a thermoelectric converter. The О2 concentration readings (ConО2) in mg/L were recorded every minute throughout 60 min. Significant intergroup differences in ConО2 values in the end of the experiment were found (р < 0.05). It has been shown that OPC increases the prostate tissue OCR in white outbred rats.
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Quasi-movements (QMs), which are  movement attempts minimized to the point of movement extinction, evoke EEG patterns similar to those of real movement. QMs can model attempted movement in healthy subjects and are therefore of interest as an alternative to motor imagery (MI) in rehabilitation brain–computer interfaces (BCIs), in which the attempted movement of the paralyzed limb is used as a control signal. Earlier QM studies were focused on thumb abduction. The study aimed to verify the feasibility of QMs based on more natural actions (pressing and pointing) and compare their EEG correlates with those of MI. In 11 healthy volunteers (6 women, aged 21–32), EEG recording was performed during execution of MI, non-goal-directed QMs (nQMs), goal-directed QMs (gQMs), and real movements. Both QM types caused more pronounced contralateral desynchronization of the 8–13 Hz mu rhythm than MI (0.63 dB, effect of movement type, p = 0.042), while nQMs and gQMs did not differ. There were no differences in ipsilateral desynchronization between the conditions (p = 0.216). Pairwise comparisons were significant in the upper-frequency mu rhythm sub-range (nQM–MI: 0.82 dB, p = 0.003; gQM–MI: 0.70 dB, p = 0.022). There was no effect of movement type in the parietal area of interest (p = 0.15). The contribution of residual movement was non-significant. The data obtained show that QMs based on natural actions are feasible and produce stronger sensorimotor activation than MI, which justifies further research focused on QMs in the context of rehabilitation BCIs.
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In recent years, the number of emergencies, armed conflicts, and household injuries has increased, which has elevated the risk of thermal burns for a broad segment of the population. Design and testing of new, safe and efficient burn-healing drugs remains a relevant task. This study aimed to evaluate the burn — healing effects of a new cream containing polyprenols isolated from Ginkgo biloba L. in a rat thermal-burn model. The cream's active ingredient is a highly purified (≥ 95%) Ginkgo biloba L. polyprenols, and the excipients are lipids (phosphatidylcholine, phosphatidylserine) with tocopherol antioxidants. The experimental animals were 32 male Wistar rats weighing 280–320 g. We evaluated the effect of the new polyprenol cream and the reference preparations methyluracil and dexpanthenol on the dynamics of the skin lesion area in rats with grade III-B skin burns. The experiment showed that, on day 21 after the burn, the new cream reduced the wound area in rats by 2.3 times compared with the controls. Morphological examination showed that the new cream had a 1.3-fold better burn-healing effect than the comparison drug methyluracil (dioxomethyltetrahydropyrimidine). Further preclinical study of the cream as a potential burn and wound healing agent seems promising.
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External genital endometriosis is characterized by high prevalence. Despite unquestionable role of oxidative stress in the development of endometriosis, its features associated with the disease progression are poorly understood. The study aimed to assess the role of oxidative protein modification (OPM) products in the disease progression. A total of 28 women with the established and histologically verified diagnosis of endometriosis took part in the study. The subjects were stratified into group 1 (stage II–III, n = 10) and group 2 (stage IV, n = 18) based on the disease stage in accordance with the American Association of Gynecologic Laparoscopists (AAGL) classification. The content of OPM products in the ectopic endometrium homogenate was determined by spectrophotometry. The following indicators were significantly higher in patients of group 2, than in patients of group 1: the total OPM product content (p = 0.040), basic aldehyde-dinitrophenylhydrazones (p = 0.039), and the total amount of ketone-dinitrophenylhydrazones (p = 0.024). Furthermore, women of group 2 showed significantly lower reserve-adaptative potential values, than patients of group 1 (p = 0.045). We found a positive correlation between the disease severity and the content of OPM products showing intergroup differences (R between 0.397 and 0.443, p < 0.05), along with the negative correlation with the reserve-adaptative potential (R = –0.388, p = 0.042) based on the correlation analysis results. According to the data obtained, the oxidative stress activity in endometriosis foci was correlated with the disease severity. Furthermore, accumulation of OPM products and depletion of the tissue adaptive capacity are typical.
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Reconstruction of peripheral nerves remains an urgent surgical problem. Autologous nerve grafting is the gold standard for bridging nerve defects, but it is limited by the shortage of donor material, which drives interest in biocompatible polymers for artificial conduits. The aim of this study was to evaluate biocompatibility in vitro and tissue response to subcutaneous in vivo implantation of perspective microstructured materials. The cytotoxicity of porous polycaprolactone (PCL), PCL–collagen composite, fibrous PCL, and nanofibrous polyamide was assessed on L929 fibroblasts. For in vivo testing, material samples were implanted into C57BL/6 mice, and histological analysis was performed after 14 days. In vitro porous PCL exhibited the highest viability and adhesion, while fibrous PCL showed the lowest. In vivo porous PCL and nanofibrous polyamide caused minimal inflammation, whereas PCL–collagen composite and fibrous PCL induced granulomatous inflammation, macrophage infiltration, and formation of fibrous capsule. The most biocompatible materials — porous PCL and nanofibrous polyamide — show promise for a biomimetic conduit with an outer barrier shell of porous PCL and an inner aligned scaffold of polyamide nanofibers.
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