Direct pro-neural reprogramming is a conversion of differentiated somatic cells to neural cells without an intermediate pluripotency stage. It is usually achieved via ectopic expression (EE) of certain transcription factors (TFs) or other reprogramming factors (RFs). Determining the transcriptional changes (TCs) caused by particular RFs in a given cell line enables an informed approach to reprogramming initiation.
View Article and Find Full Text PDFBackground: Standard approaches to the treatment of chronic post-radiation proctitis are associated with a high risk of complications and a high percentage of unsatisfactory results due to the reduced regenerative potential of irradiated tissues. Regenerative surgery techniques using the stromal-vascular cell fraction (SVF) based on the patient's autologous adipose tissue are a promising direction for study.
Clinical Case Description: A 76-year-old patient suffering from chronic post-radiation erosive-ulcerative proctitis, grade 4 according to RTOG-EORTC, complicated by recurrent profuse rectal bleeding, underwent local autotransplantation of SVF into the submucosal layer of the rectum and pararectal connective tissue.
Glioblastoma (GBM) is the most common malignancy of the central nervous system in adults. GBM has high levels of therapy failure and its prognosis is usually dismal. The phenotypic heterogeneity of the tumor cells, dynamic complexity of non-tumor cell populations within the GBM tumor microenvironment (TME), and their bi-directional cross-talk contribute to the challenges of current therapeutic approaches.
View Article and Find Full Text PDFDynamic changes in genomic DNA methylation patterns govern the epigenetic developmental programs and accompany the organism's aging. Epigenetic clock (eAge) algorithms utilize DNA methylation to estimate the age and risk factors for diseases as well as analyze the impact of various interventions. High-throughput bisulfite sequencing methods, such as reduced-representation bisulfite sequencing (RRBS) or whole genome bisulfite sequencing (WGBS), provide an opportunity to identify the genomic regions of disordered or heterogeneous DNA methylation, which might be associated with cell-type heterogeneity, DNA methylation erosion, and allele-specific methylation.
View Article and Find Full Text PDFSpinal cord injury (SCI) is a medical condition affecting ~2.5-4 million people worldwide. The conventional therapy for SCI fails to restore the lost spinal cord functions; thus, novel therapies are needed.
View Article and Find Full Text PDFAntibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (RBD S-protein) contribute significantly to the humoral immune response during coronavirus infection (COVID-19) and after vaccination. The main focus of the studies of the RBD epitope composition is usually concentrated on the epitopes recognized by the virus-neutralizing antibodies. The role of antibodies that bind to RBD but do not neutralize SARS-CoV-2 remains unclear.
View Article and Find Full Text PDFSince the onset of the COVID-19 pandemic, humanity has experienced the spread and circulation of several SARS-CoV-2 variants that differed in transmissibility, contagiousness, and the ability to escape from vaccine-induced neutralizing antibodies. However, issues related to the differences in the variant-specific immune responses remain insufficiently studied. The aim of this study was to compare the parameters of the humoral immune responses in two groups of patients with acute COVID-19 who were infected during the circulation period of the D614G and the Delta variants of SARS-CoV-2.
View Article and Find Full Text PDFCancer virotherapy is an alternative therapeutic approach based on the viruses that selectively infect and kill tumor cells. Vaccinia virus (VV) is a member of the Poxviridae, a family of enveloped viruses with a large linear double-stranded DNA genome. The proven safety of the VV strains as well as considerable transgene capacity of the viral genome, make VV an excellent platform for creating recombinant oncolytic viruses for cancer therapy.
View Article and Find Full Text PDFThe acoustic waves of higher orders propagating in a layered structure consisting of a silicon plate coated with piezoelectric and/or films were used for the development of a sensor with selective sensitivity to liquid viscosity in the range of 1-1500 cP. In that range, this sensor possessed low sensitivity to liquid conductivity and temperature T in the ranges of 0-2 S/m and 0-55 °C, respectively. The amplitude responses insensitive to the temperature instead of the phase were used to provide the necessary selectivity.
View Article and Find Full Text PDFAntibody-dependent enhancement (ADE) has been shown previously for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 infection in vitro. In this study, the first monoclonal antibody (mAb) that causes ADE in a SARS-CoV-2 in vivo model was identified. mAb RS2 against the SARS-CoV-2 S-protein was developed using hybridoma technology.
View Article and Find Full Text PDFUnlabelled: Patient-specific tumor models are a promising platform for studying the mechanisms of oncogenesis and personalized selection of drugs. In case of glial brain tumors, development and use of such models is particularly relevant as the effectiveness of such tumor treatment remains extremely unsatisfactory. was to develop a model of a 3D tumor glioblastoma spheroid based on a patient's surgical material and to study its metabolic characteristics by means of fluorescence lifetime imaging microscopy of metabolic coenzymes.
View Article and Find Full Text PDFWe developed recombinant variants of oncolytic vaccinia virus LIVP strain expressing interleukin-15 (IL-15) or its receptor subunit alpha (IL-15Rα) to stimulate IL-15-dependent immune cells. We evaluated their oncolytic activity either alone or in combination with each other and using the murine CT26 colon carcinoma and 4T1 breast carcinoma models. We demonstrated that the admixture of these recombinant variants could promote the generation of the IL-15/IL-15Rα complex.
View Article and Find Full Text PDFHepatitis C virus (HCV) is one of the basic culprits behind chronic liver disease, which may result in cirrhosis and hepatocarcinoma. In spite of the extensive research conducted, a vaccine against HCV has not been yet created. We have obtained human mesenchymal stem cells (hMSCs) and used them for expressing the HCV NS5A protein as a model vaccination platform.
View Article and Find Full Text PDFThe effectiveness of the antiviral immune response largely depends on the activation of cytotoxic T cells. The heterogeneous group of functionally active T cells expressing the CD56 molecule (NKT-like cells), that combines the properties of T lymphocytes and NK cells, is poorly studied in COVID-19. This work aimed to analyze the activation and differentiation of both circulating NKT-like cells and CD56 T cells during COVID-19 among intensive care unit (ICU) patients, moderate severity (MS) patients, and convalescents.
View Article and Find Full Text PDFOncolytic viral therapy is a promising novel approach to cancer treatment. Oncolytic viruses cause tumor regression through direct cytolysis on the one hand and recruiting and activating immune cells on the other. In this study, to enhance the antitumor efficacy of the thymidine kinase-deficient vaccinia virus (VV, Lister strain), recombinant variants encoding bacterial flagellin (subunit B) of (LIVP-FlaB-RFP), firefly luciferase (LIVP-Fluc-RFP) or red fluorescent protein (LIVP-RFP) were developed.
View Article and Find Full Text PDFTHz radiation induces a variety of processes in cells and has attracted the attention of researchers in recent decades. Here, data on the effects of high-intensity terahertz (THz) radiation on human directly reprogrammed neural progenitor cells (drNPCs) and on neuroblastoma cells (SK-N-BE (2)) were obtained for the first time. The results demonstrated that the exposure of non-tumor and tumor cells to broadband (0.
View Article and Find Full Text PDFGlioblastoma is the most aggressive form of malignant brain tumor. Standard treatment protocols and traditional immunotherapy are poorly effective as they do not significantly increase the long-term survival of glioblastoma patients. Oncolytic viruses (OVs) may be an effective alternative approach.
View Article and Find Full Text PDFCoronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is accompanied by a dysregulated immune response. In particular, NK cells, involved in the antiviral response, are affected by the infection. This study aimed to investigate circulating NK cells with a focus on their activation, depletion, changes in the surface expression of key receptors, and functional activity during COVID-19, among intensive care unit (ICU) patients, moderately ill patients, and convalescents (CCP).
View Article and Find Full Text PDFSevere acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and rapidly caused a pandemic that led to the death of >6 million people due to hypercoagulation and cytokine storm. In addition, SARS-CoV-2 triggers a wide array of pathologies, including liver dysfunction and neurological disorders. It remains unclear if these events are due to direct infection of the respective tissues or result from systemic inflammation.
View Article and Find Full Text PDFThe parameters of the humoral response are an important immunological characteristic of donors who recovered from COVID-19 and vaccinated individuals. Analysis of the level of virus-binding antibodies has become widespread. The most accurate predictor of effective immune protection against symptomatic SARS-CoV-2 infection is the activity of virus-neutralizing antibodies.
View Article and Find Full Text PDFThe parameters of the humoral response are an important immunological characteristic of donors who recovered from COVID-19 and vaccinated individuals. Analysis of the level of virus-binding antibodies has become widespread. The most accurate predictor of effective immune protection against symptomatic SARS-CoV-2 infection is the activity of virus-neutralizing antibodies.
View Article and Find Full Text PDFVitamin D as an immunomodulator has not been studied in patients with severe COVID-19. This study aimed to estimate the efficacy of vitamin D3 supplementation on cellular immunity and inflammatory markers in patients with COVID-19 admitted to the intensive care unit (ICU). A single-center, double-blind, randomized, placebo-controlled pilot trial was conducted (N = 110).
View Article and Find Full Text PDFThe data is obtained on the effect of high-intensity pulses of terahertz (THz) radiation with a broad spectrum (0.2-3 THz) on cell cultures. We have evaluated the threshold exposure parameters of THz radiation causing genotoxic effects in fibroblasts.
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