8 research outputs found

    Serum BDNF's Role as a Biomarker for Motor Training in the Context of AR-Based Rehabilitation after Ischemic Stroke

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    BACKGROUND: brain-derived neurotrophic factor (BDNF) may play a role during neurorehabilitation following ischemic stroke. This study aimed to elucidate the possible role of BDNF during early recovery from ischemic stroke assisted by motor training. METHODS: fifty patients were included after acute recovery from ischemic stroke: 21 first received classical rehabilitation followed by 'motor rehabilitation using motion sensors and augmented reality' (AR-rehabilitation), 14 only received AR-rehabilitation, and 15 were only observed. Serum BDNF levels were measured on the first day of stroke, on the 14th day, before AR-based rehabilitation (median, 45th day), and after the AR-based rehabilitation (median, 82nd day). Motor impairment was quantified clinically using the Fugl-Meyer scale (FMA); functional disability and activities of daily living (ADL) were measured using the Modified Rankin Scale (mRS). For comparison, serum BDNF was measured in 50 healthy individuals. RESULTS: BDNF levels were found to significantly increase during the phase with AR-based rehabilitation. The pattern of the sequentially measured BDNF levels was similar in the treated patients. Untreated patients had significantly lower BDNF levels at the endpoint. CONCLUSIONS: the fluctuations of BDNF levels are not consistently related to motor improvement but seem to react to active treatment. Without active rehabilitation treatment, BDNF tends to decrease

    Structure- and interaction-based design of anti-SARS-CoV-2 aptamers

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    Aptamer selection against novel infections is a complicated and time-consuming approach. Synergy can be achieved by using computational methods together with experimental procedures. This study aims to develop a reliable methodology for a rational aptamer in silico et vitro design. The new approach combines multiple steps: (1) Molecular design, based on screening in a DNA aptamer library and directed mutagenesis to fit the protein tertiary structure; (2) 3D molecular modeling of the target; (3) Molecular docking of an aptamer with the protein; (4) Molecular dynamics (MD) simulations of the complexes; (5) Quantum-mechanical (QM) evaluation of the interactions between aptamer and target with further analysis; (6) Experimental verification at each cycle for structure and binding affinity by using small-angle X-ray scattering, cytometry, and fluorescence polarization. By using a new iterative design procedure, structure- and interaction-based drug design (SIBDD), a highly specific aptamer to the receptorbinding domain of the SARS-CoV-2 spike protein, was developed and validated. The SIBDD approach enhances speed of the high-affinity aptamers development from scratch, using a target protein structure. The method could be used to improve existing aptamers for stronger binding. This approach brings to an advanced level the development of novel affinity probes, functional nucleic acids. It offers a blueprint for the straightforward design of targeting molecules for new pathogen agents and emerging variant

    Clinical and microbiological evaluation of the efficacy of autoprobiotics in the combination treatment of chronic generalized periodontitis

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    Combination treatment of patients with inflammatory periodontal diseases may be ineffective due to the variability of periodontal pathogens and the polyetiology of the disease. This disadvantage can be overcome by using highly antagonistic, enzymatic, and immunostimulating drugs, in addition to the main treatment. The objective of this study is to evaluate the efficacy of autoprobiotics clinically and microbiologically in the combination treatment of chronic generalized periodontitis. The presented study involved a survey of 37 patients aged 29 to 64 years with mild chronic generalized periodontitis. The patients were divided into three groups. Group I consisted of patients whose combination treatment included an S. salivarius-based autoprobiotic (subgroup 1 - patients who had their periodontal pockets irrigated with an autoprobiotic, subgroup 2 - patients who used oral baths with autoprobiotic). Group II consisted of patients who used a common S. salivarius-based probiotic in combination treatment (subgroup 1 - patients who had their periodontal pockets irrigated with a probiotic, subgroup 2 - patients who used oral baths with a probiotic). The control group consisted of patients with mild chronic generalized periodontitis, whose combination treatment consisted of professional oral hygiene and correction of individual hygiene. Microbiological examination of the content of periodontal pockets was carried out using PCR screening for periodontal pathogens, such as P. gingivalis, T. denticola, T. forsythia, P. intermedia. Based on the clinical and microbiological results of the study, the efficacy of an autoprobiotic and probiotic based on S. salivarius in the combination treatment of mild chronic generalized periodontitis was demonstrated

    Multicomponent synthesis of artificial nucleases and their RNase and DNase activity

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    The synthesis of new, artificial ribonucleases containing two amino acid residues connected by an aliphatic linker has been developed. Target molecules were synthesized via a catalytic three-component Ugi reaction from aliphatic diisocyanides. Preliminary investigations proved unspecific nuclease activity of the new compounds towards single-stranded RNA and double-stranded circular DNA

    Changes in the Ultrastructure of <i>Staphylococcus aureus</i> Cells Make It Possible to Identify and Analyze the Injuring Effects of Ciprofloxacin, Polycationic Amphiphile and Their Hybrid

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    The purposeful development of synthetic antibacterial compounds requires an understanding of the relationship between effects of compounds and their chemical structure. This knowledge can be obtained by studying changes in bacteria ultrastructure under the action of antibacterial compounds of a certain chemical structure. Our study was aimed at examination of ultrastructural changes in S. aureus cells caused by polycationic amphiphile based on 1,4‒diazabicyclo[2.2.2]octane (DL412), ciprofloxacin and their hybrid (DL5Cip6); the samples were incubated for 15 and 45 min. DL412 first directly interacted with bacterial cell wall, damaging it, then penetrated into the cell and disrupted cytoplasm. Ciprofloxacin penetrated into cell without visually damaging the cell wall, but altered the cell membrane and cytoplasm, and inhibited the division of bacteria. The ultrastructural characteristics of S. aureus cells damaged by the hybrid clearly differed from those under ciprofloxacin or DL412 action. Signs associated with ciprofloxacin predominated in cell damage patterns from the hybrid. We studied the effect of ciprofloxacin, DL412 and their hybrid on S. aureus biofilm morphology using paraffin sections. Clear differences in compound effects on S. aureus biofilm (45 min incubation) were observed. The results obtained allow us to recommend this simple and cheap approach for the initial assessment of antibiofilm properties of synthesized compounds

    Biocompatibility of Small-Diameter Vascular Grafts in Different Modes of RGD Modification

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    Modification with Arg-Gly-Asp (RGD) peptides is a promising approach to improve biocompatibility of small-calibre vascular grafts but it is unknown how different RGD sequence composition impacts graft performance. Here we manufactured 1.5 mm poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(&epsilon;-caprolactone) grafts modified by distinct linear or cyclic RGD peptides immobilized by short or long amine linker arms. Modified vascular prostheses were tested in vitro to assess their mechanical properties, hemocompatibility, thrombogenicity and endothelialisation. We also implanted these grafts into rat abdominal aortas with the following histological examination at 1 and 3 months to evaluate their primary patency, cellular composition and detect possible calcification. Our results demonstrated that all modes of RGD modification reduce ultimate tensile strength of the grafts. Modification of prostheses does not cause haemolysis upon the contact with modified grafts, yet all the RGD-treated grafts display a tendency to promote platelet aggregation in comparison with unmodified counterparts. In vivo findings identify that cyclic Arg-Gly-Asp-Phe-Lys peptide in combination with trioxa-1,13-tridecanediamine linker group substantially improve graft biocompatibility. To conclude, here we for the first time compared synthetic small-diameter vascular prostheses with different modes of RGD modification. We suggest our graft modification regimen as enhancing graft performance and thus recommend it for future use in tissue engineering

    Structure- and Interaction-Based Design of Anti-SARS-CoV-2 Aptamers

    Get PDF
    Aptamer selection against novel infections is a complicated and time-consuming approach. Synergy can be achieved by using computational methods together with experimental procedures. This study aims to develop a reliable methodology for a rational aptamer in silico et vitro design. The new approach combines multiple steps: (1) Molecular design, based on screening in a DNA aptamer library and directed mutagenesis to fit the protein tertiary structure; (2) 3D molecular modeling of the target; (3) Molecular docking of an aptamer with the protein; (4) Molecular dynamics (MD) simulations of the complexes; (5) Quantum-mechanical (QM) evaluation of the interactions between aptamer and target with further analysis; (6) Experimental verification at each cycle for structure and binding affinity using small-angle X-ray scattering, cytometry, and fluorescence polarization. Using a new iterative design procedure, Interaction Based Drug Design (SIBDD), a highly specific aptamer to the receptor-binding domain of the SARS-CoV-2 spike protein, was developed and validated. The SIBDD approach enhances speed of the high-affinity aptamers development from scratch, using a target protein structure. The method could be used to improve existing aptamers for stronger binding. This approach brings to an advanced level the development of novel affinity probes, functional nucleic acids. It offers a blueprint for the straightforward design of targeting molecules for new pathogen agents and emerging variants.peerReviewe
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