Репозиторий Университета

Mechanisms of homeostatic plasticity promote compensatory changes of cellular excitability in response to chronic changes in the network activity. This type of plasticity is essential for the maintenance of brain circuits and is involved in the regulation of neural regeneration and the progress of neurodegenerative disorders. One of the most studied homeostatic processes is synaptic scaling, where global synaptic adjustments take place to restore the neuronal firing rate to a physiological range by the modulation of synaptic receptors, neurotransmitters, and morphology. However, despite the comprehensive literature on the electrophysiological properties of homeostatic scaling, less is known about the structural adjustments that occur in the synapses and dendritic tree. In this study, we performed a meta-analysis of articles investigating the effects of chronic network excitation (synaptic downscaling) or inhibition (synaptic upscaling) on the dendritic spine density of neurons. Our results indicate that spine density is consistently reduced after protocols that induce synaptic scaling, independent of the intervention type. Then, we discuss the implication of our findings to the current knowledge on the morphological changes induced by homeostatic plasticity.

The development of laser medicine has led to its use in dentistry further to improve existing treatment methods, including surgical techniques. The variety of lasers allows them to be used for procedures on the soft and bone tissues of the oral cavity as well as on the tissues of the teeth. The short duration of laser pulse action on tissues, selective action on pathological tissues in a sterile surgical field, and activation of local and humoral immunity of the oral cavity provides an increase in the regeneration potential of tissues of the postoperative area, which contributes to the shortening of wound process phases, favorable course of the postoperative period, and shortening of the healing time. Our article presents the experience of using the Nd:YAG laser in different modes in replicating the effect of curettage of periodontal pockets in an experiment on laboratory animals. According to the study results, there was a difference in the healing time of soft tissues after their exposure to several modes of the Nd:YAG laser, which makes it possible to recommend each of them for individual clinical cases.

Recently, zinc and its alloys have been proposed as promising candidates for biodegradable metals (BMs), owning to their preferable corrosion behavior and acceptable biocompatibility in cardiovascular, bone and gastrointestinal environments, together with Mg-based and Fe-based BMs. However, there is the desire for surface treatment for Zn-based BMs to better control their biodegradation behavior. Firstly, the implantation of some Zn-based BMs in cardiovascular environment exhibited intimal activation with mild inflammation. Secondly, for orthopedic applications, the biodegradation rates of Zn-based BMs are relatively slow, resulting in a long-term retention after fulfilling their mission. Meanwhile, excessive Zn2+ release during degradation will cause in vitro cytotoxicity and in vivo delayed osseointegration. In this review, we firstly summarized the current surface modification methods of Zn-based alloys for the industrial applications. Then we comprehensively summarized the recent progress of biomedical bulk Zn-based BMs as well as the corresponding surface modification strategies. Last but not least, the future perspectives towards the design of surface bio-functionalized coatings on Zn-based BMs for orthopedic and cardiovascular applications were also briefly proposed.

Thanks to their biocompatibility, biodegradability, injectability and self-setting properties, calcium phosphate cements (CPCs) have been the most economical and effective biomaterials of choice for use as bone void fillers. They have also been extensively used as drug delivery carriers owing to their ability to provide for a steady release of various organic molecules aiding the regeneration of defective bone, including primarily antibiotics and growth factors. This review provides a systematic compilation of studies that reported on the controlled release of drugs from CPCs in the last 25 years. The chemical, compositional and microstructural characteristics of these systems through which the control of the release rates and mechanisms could be achieved have been discussed. In doing so, the effects of (i) the chemistry of the matrix, (ii) porosity, (iii) additives, (iv) drug types, (v) drug concentrations, (vi) drug loading methods and (vii) release media have been distinguished and discussed individually. Kinetic specificities of in vivo release of drugs from CPCs have been reviewed, too. Understanding the kinetic and mechanistic correlations between the CPC properties and the drug release is a prerequisite for the design of bone void fillers with drug release profiles precisely tailored to the application area and the clinical picture. The goal of this review has been to shed light on these fundamental correlations.

Recently, zinc and its alloys have been proposed as promising candidates for biodegradable metals (BMs), owning to their preferable corrosion behavior and acceptable biocompatibility in cardiovascular, bone and gastrointestinal environments, together with Mg-based and Fe-based BMs. However, there is the desire for surface treatment for Zn-based BMs to better control their biodegradation behavior. Firstly, the implantation of some Zn-based BMs in cardiovascular environment exhibited intimal activation with mild inflammation. Secondly, for orthopedic applications, the biodegradation rates of Zn-based BMs are relatively slow, resulting in a long-term retention after fulfilling their mission. Meanwhile, excessive Zn2+ release during degradation will cause in vitro cytotoxicity and in vivo delayed osseointegration. In this review, we firstly summarized the current surface modification methods of Zn-based alloys for the industrial applications. Then we comprehensively summarized the recent progress of biomedical bulk Zn-based BMs as well as the corresponding surface modification strategies. Last but not least, the future perspectives towards the design of surface bio-functionalized coatings on Zn-based BMs for orthopedic and cardiovascular applications were also briefly proposed.

Thanks to their biocompatibility, biodegradability, injectability and self-setting properties, calcium phosphate cements (CPCs) have been the most economical and effective biomaterials of choice for use as bone void fillers. They have also been extensively used as drug delivery carriers owing to their ability to provide for a steady release of various organic molecules aiding the regeneration of defective bone, including primarily antibiotics and growth factors. This review provides a systematic compilation of studies that reported on the controlled release of drugs from CPCs in the last 25 years. The chemical, compositional and microstructural characteristics of these systems through which the control of the release rates and mechanisms could be achieved have been discussed. In doing so, the effects of (i) the chemistry of the matrix, (ii) porosity, (iii) additives, (iv) drug types, (v) drug concentrations, (vi) drug loading methods and (vii) release media have been distinguished and discussed individually. Kinetic specificities of in vivo release of drugs from CPCs have been reviewed, too. Understanding the kinetic and mechanistic correlations between the CPC properties and the drug release is a prerequisite for the design of bone void fillers with drug release profiles precisely tailored to the application area and the clinical picture. The goal of this review has been to shed light on these fundamental correlations.

The local crystal/magnetic structures of the SrFe12−xInxO19 solid solutions (x = 0.1; 0.3; 0.6 and 1.2) were investigated using neutron powder diffraction. The measurements of the electric polarization for all investigated samples were carried out as a function of the external electric field. The presence of the ferroelectric and ferromagnetic ordering (dual ferroic ordering) in the SrFe12−xInxO19 hexaferrites at 300 K was found. This appearance contradicts to the conventional opinion describing their crystal structure (centrosymmetric space group P63/mmc (No. 194)). The reason for the existence of a spontaneous polarization (nonzero dipole moment) in the SrFe12−xInxO19 hexaferrites continues controversial. The crystal structure of the hexaferrites was considered both the centrosymmetric P63/mmc and non-centrosymmetric P63mc space groups. This fact made it possible to find a connection between the emerging dipole moment and not equal distortions of the neighbor oxygen polyhedral. The nature description of the nonzero dipole moment formation in a quasi-centrosymmetrical system of the In-substituted SrFe12−xInxO19 hexaferrites was presented based on the neutron diffraction data.

The local crystal/magnetic structures of the SrFe12−xInxO19 solid solutions (x = 0.1; 0.3; 0.6 and 1.2) were investigated using neutron powder diffraction. The measurements of the electric polarization for all investigated samples were carried out as a function of the external electric field. The presence of the ferroelectric and ferromagnetic ordering (dual ferroic ordering) in the SrFe12−xInxO19 hexaferrites at 300 K was found. This appearance contradicts to the conventional opinion describing their crystal structure (centrosymmetric space group P63/mmc (No. 194)). The reason for the existence of a spontaneous polarization (nonzero dipole moment) in the SrFe12−xInxO19 hexaferrites continues controversial. The crystal structure of the hexaferrites was considered both the centrosymmetric P63/mmc and non-centrosymmetric P63mc space groups. This fact made it possible to find a connection between the emerging dipole moment and not equal distortions of the neighbor oxygen polyhedral. The nature description of the nonzero dipole moment formation in a quasi-centrosymmetrical system of the In-substituted SrFe12−xInxO19 hexaferrites was presented based on the neutron diffraction data.

© 2021, The Author(s). Background: The acute phase response (APR) to CNS insults contributes to the overall magnitude and nature of the systemic inflammatory response. Aspects of this response are thought to drive secondary inflammatory pathology at the lesion site, and suppression of the APR can therefore afford some neuroprotection. In this study, we examined the APR in a mouse model of traumatic spinal cord injury (SCI), along with its relationship to neutrophil recruitment during the immediate aftermath of the insult. We specifically investigated the effect of IL-1 receptor antagonist (IL-1RA) administration on the APR and leukocyte recruitment to the injured spinal cord. Methods: Adult female C57BL/6 mice underwent either a 70kD contusive SCI, or sham surgery, and tissue was collected at 2, 6, 12, and 24 hours post-operation. For IL-1RA experiments, SCI mice received two intraperitoneal injections of human IL-1RA (100mg/kg), or saline as control, immediately following, and 5 hours after impact, and animals were sacrificed 6 hours later. Blood, spleen, liver and spinal cord were collected to study markers of central and peripheral inflammation by flow cytometry, immunohistochemistry and qPCR. Results were analysed by two-way ANOVA or student’s t-test, as appropriate. Results: SCI induced a robust APR, hallmarked by elevated hepatic expression of pro-inflammatory marker genes and a significantly increased neutrophil presence in the blood, liver and spleen of these animals, as early as 2 hours after injury. This peripheral response preceded significant neutrophil infiltration of the spinal cord, which peaked 24 hours post-SCI. Although expression of IL-1RA was also induced in the liver following SCI, its response was delayed compared to IL-1β. Exogenous administration of IL-1RA during this putative therapeutic window was able to suppress the hepatic APR, as evidenced by a reduction in CXCL1 and SAA-2 expression as well as a significant decrease in neutrophil infiltration in both the liver and the injured spinal cord itself. Conclusions: Our data indicate that peripheral administration of IL-1RA can attenuate the APR which in turn reduces immune cell infiltration at the spinal cord lesion site. We propose IL-1RA treatment as a viable therapeutic strategy to minimise the harmful effects of SCI-induced inflammation.

© 2021, The Author(s). Background: Non-steroidal anti-inflammatory drugs such as aspirin are used for the treatment of cardiovascular disease. Chronic use of low-dose aspirin is associated with the occurrence of gastric ulcer. The aim of this study was to investigate the healing potential of Lycium barbarum polysaccharides (LBP) from Chinese Goji berry and C-phycocyanin (CPC) from Spirulina platensis on gastric ulcer in rats. Methods: Male Sprague–Dawley rats were divided into five groups: normal, aspirin (700 mg/kg bw), LBP (aspirin + 100 mg/kg bw/d LBP), CPC (aspirin + 50 mg/kg bw/d CPC), and MIX (aspirin + 50 mg/kg bw/d LBP + 25 mg/kg bw/d CPC) groups. Gastric ulcer was developed by daily oral feeding of aspirin for 8 weeks. Treatments were given orally a week before ulcer induction for 9 weeks. Results: The MIX group elevated gastric cyclooxygenase-1, prostaglandin E2, and total nitrite and nitrate levels by 139%, 86%, and 66%, respectively, compared with the aspirin group (p < 0.05). Moreover, the MIX group reduced lipid peroxides malondialdehyde levels by 78% (p < 0.05). The treatment of LBP and/or CPC increased gastric Bifidobacterium relative abundance by 2.5–4.0 times compared with the aspirin group (p < 0.05). Conclusions: We conclude that combined LBP and CPC enhance gastroprotective factors, inhibit lipid peroxidation, and increase gastric Bifidobacterium relative abundance. Combined LBP and CPC have protective potential against gastric ulcer caused by aspirin in rats.

© 2021, The Author(s). Background: Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods: A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results: By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

© 2021, The Author(s). Background: Non-steroidal anti-inflammatory drugs such as aspirin are used for the treatment of cardiovascular disease. Chronic use of low-dose aspirin is associated with the occurrence of gastric ulcer. The aim of this study was to investigate the healing potential of Lycium barbarum polysaccharides (LBP) from Chinese Goji berry and C-phycocyanin (CPC) from Spirulina platensis on gastric ulcer in rats. Methods: Male Sprague–Dawley rats were divided into five groups: normal, aspirin (700 mg/kg bw), LBP (aspirin + 100 mg/kg bw/d LBP), CPC (aspirin + 50 mg/kg bw/d CPC), and MIX (aspirin + 50 mg/kg bw/d LBP + 25 mg/kg bw/d CPC) groups. Gastric ulcer was developed by daily oral feeding of aspirin for 8 weeks. Treatments were given orally a week before ulcer induction for 9 weeks. Results: The MIX group elevated gastric cyclooxygenase-1, prostaglandin E2, and total nitrite and nitrate levels by 139%, 86%, and 66%, respectively, compared with the aspirin group (p < 0.05). Moreover, the MIX group reduced lipid peroxides malondialdehyde levels by 78% (p < 0.05). The treatment of LBP and/or CPC increased gastric Bifidobacterium relative abundance by 2.5–4.0 times compared with the aspirin group (p < 0.05). Conclusions: We conclude that combined LBP and CPC enhance gastroprotective factors, inhibit lipid peroxidation, and increase gastric Bifidobacterium relative abundance. Combined LBP and CPC have protective potential against gastric ulcer caused by aspirin in rats.

© 2021, The Author(s). Background: Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods: A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results: By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

© 2021, The Author(s). Background: HIV infection is a major health problem in Russia. We aimed to assess HIV prevalence in different population groups and to compare the characteristics of 4th generation immunoassays from Abbott, Bio-Rad, Vector-Best, Diagnostic Systems, and Medical Biological Unit. Methods: The study included 4452 individuals from the general population (GP), 391 subjects at high risk of HIV infection (HR) and 699 with potentially interfering conditions. HIV positivity was confirmed by immunoblot and by HIV RNA, seroconversion and virus diversity panels were also used. HIV avidity was employed to assess recent infections. Results: The prevalence in GP was 0.40%, higher in males (0.62%) and in people aged < 40 years (0.58%). Patients attending dermo-venereal centers and drug users had a high prevalence (34.1 and 58.8%). Recent infections were diagnosed in 20% of GP and in 4.2% of HR. Assay sensitivity was 100% except for one false negative (99,54%, MBU). Specificity was 99.58–99.89% overall, but as low as 93.26% on HR (Vector-Best). Small differences on early seroconversion were recorded. Only the Abbott assay detected all samples on the viral diversity panel. Conclusion: HIV infection rate in the high-risk groups suggests that awareness and screening campaigns should be enhanced. Fourth generation assays are adequate but performance differences must be considered.

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Persistent organic pollutants (POPs) are heterogeneous carbon-based compounds that can seriously affect human health. The aim of this study was to measure serum concentrations of POPs in women residing in the Euro-Arctic Region of Russia. A total of 204 women from seven rural settlements of the Nenets Autonomous Okrug (NAO) took part in the study. We measured serum concentrations of 11 polychlorinated biphenyls (PCBs) and 17 organochlorine pesticides (OCPs) across the study sites and among Nenets and non-Nenets residents. Measurement of POPs was performed using an Agilent 7890A gas chromatograph equipped with an Agilent 7000 series MS/MS triple quadrupole system. The concentrations of all POPs were low and similar to findings from other Arctic countries. However, significant geographic differences between the settlements were observed with exceptionally high concentrations of PCBs in Varnek located on Vaygach Island. Both ΣDDT (p = 0.011) and ΣPCB (p = 0.038) concentrations were significantly lower in Nenets. Our main findings suggest that the serum concentrations of the legacy POPs in women in the Euro-Arctic Region of Russia are low and similar to those in other Arctic countries. Significant variations between settlements, and between Nenets and non-Nenets residents, were found. Arctic biomonitoring research in Russia should include studies on the associations between nutrition and concentrations of POPs.

© 2021, The Author(s). Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.

© 2021, The Author(s). Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.

© 2021, The Author(s). Cell transmembrane receptors and extracellular matrix components play a pivotal role in regulating cell activity and providing for the concerted integration of cells in the tissue structures. We have assessed DNA methylation in the promoter regions of eight integrin genes, two nidogen genes, and the dystroglycan gene in normal breast tissues and breast carcinomas (BC). The protein products of these genes interact with the basement membrane proteins LAMA1, LAMA2, and LAMB1; abnormal hypermethylation of the LAMA1, LAMA2, and LAMB1 promoters in BC has been described in our previous publications. In the present study, the frequencies of abnormal promoter hypermethylation in BC were 13% for ITGA1, 31% for ITGA4, 4% for ITGA7, 39% for ITGA9, 38% for NID1, and 41% for NID2. ITGA2, ITGA3, ITGA6, ITGB1, and DAG1 promoters were nonmethylated in normal and BC samples. ITGA4, ITGA9, and NID1 promoter hypermethylation was associated with the HER2 positive tumors, and promoter hypermethylation of ITGA1, ITGA9, NID1 and NID2 was associated with a genome-wide CpG island hypermethylated BC subtype. Given that ITGA4 is not expressed in normal breast, one might suggest that its abnormal promoter hypermethylation in cancer is non-functional and is thus merely a passenger epimutation. Yet, this assumption is not supported by our finding that it is not associated with a hypermethylated BC subtype. ITGA4 acquires expression in a subset of breast carcinomas, and methylation of its promoter may be preventive against expression in some tumors. Strong association of abnormal ITGA4 hypermethylation with the HER2 positive tumors (p = 0.0025) suggests that simultaneous presence of both HER2 and integrin α4 receptors is not beneficial for tumor cells. This may imply HER2 and integrin α4 signaling pathways interactions that are yet to be discovered.