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Biomechanical properties of blood plasma extracellular vesicles revealed by atomic force microscopy
No full textWhile extracellular vesicles (EVs) are extensively studied by various practical applications in biomedicine, there is still little information on their biomechanical properties due to their nanoscale size. We identified isolated blood plasma vesicles that carried on biomarkers associated with exosomes and exomeres and applied atomic force microscopy (AFM) to study them at single particle level in air and in liquid. Air measurements of exosomes revealed a mechanically indented internal cavity in which highly adhesive sites were located. In contrast, the highly adhesive sites of exomeres were located at the periphery and the observed diameter of the particles was ~35 nm. In liquid, the reversible deformation of the internal cavity of exosomes was observed and a slightly deformed lipid bi-layer was identified. In contrast, exomeres were not deformed and their observed diameter was ~16 nm. The difference in diameters might be associated with a higher sorption of water film in air. The parameters we revealed correlated with the well-known structure and function for exosomes and were observed for exomeres for the first time. Our data provide a new insight into the biomechanical properties of nanoparticles and positioned AFM as an exclusive source of in situ information about their biophysical characteristics. © 2020 by the authors. Licensee MDPI, Basel, Switzerland
Genomic epidemiology of the early stages of the SARS-CoV-2 outbreak in Russia
No full textThe ongoing pandemic of SARS-CoV-2 presents novel challenges and opportunities for the use of phylogenetics to understand and control its spread. Here, we analyze the emergence of SARS-CoV-2 in Russia in March and April 2020. Combining phylogeographic analysis with travel history data, we estimate that the sampled viral diversity has originated from at least 67 closely timed introductions into Russia, mostly in late February to early March. All but one of these introductions were not from China, suggesting that border closure with China has helped delay establishment of SARS-CoV-2 in Russia. These introductions resulted in at least 9 distinct Russian lineages corresponding to domestic transmission. A notable transmission cluster corresponded to a nosocomial outbreak at the Vreden hospital in Saint Petersburg; phylodynamic analysis of this cluster reveals multiple (2-3) introductions each giving rise to a large number of cases, with a high initial effective reproduction number of 3.0 [1.9, 4.3]. © 2021, The Author(s)
Design of a self-powered triboelectric face mask
No full textUsage of a face mask has become mandatory in many countries after the outbreak of SARS-CoV-2, and its usefulness in combating the pandemic is a proven fact. There have been many advancements in the design of a face mask and the present treatise describes a face mask in which a simple triboelectric nanogenerator (TENG) with an electrocution layer may serve the purpose of filtration and deactivation of SARS-CoV-2. The proposed mask is designed with multilayer filters, in which the inner three layers act as a triboelectric (TE) filter and the outer one as an electrocution layer (EL). The viral particles experience a mildshock in EL due to the electric field produced between the electrocution layers by contact electrification. Four pairs of triboelectric series fabrics, i.e. polyvinylchloride (PVC)-nylon, polypropylene (PP)-polyurethane (PU), latex rubber-PU, polyimide (PI)-nylon are studied to establish the efficacy of the mask. The motional force exerted on triboelectric filter materials can produce sufficient electric power to activate EL. The proposed mask can be used by a wide range of people because of its triboelectric self-powering (harvesting mechanical energy from daily activities, e.g. breathing, talking or other facial movements) functionalities to ensure effective filtration efficiency. More importantly, it is expected to be potentially beneficial to slow down the devastating impact of COVID-19. © 2020 Elsevier Lt
Effect of red seaweed sulfated galactans on initial steps of complement activation in vitro
No full textThe research described here presents data on the effect of galactans of red algae, carrageenans (λ/μ/ν-, κ-, κ/β-, and ι/κ-types), and agar on complement system activation in normal human serum. The experiments were based on well surfaces coated with triggering agents for binding initiating complement components —C3 and C4. The sulfated galactans inhibited C3 binding to lipopolysaccharide with direct dependence on the sulfation degree of polysaccharides. Sulfation degree was also important in carrageenans’ capacity to reduce C4 binding to mannan. However, C4 binding to antibodies was considerably activated by carrageenans, especially with 3,6-anhydrogalactose. The gelling carrageenans were able to block antigen binding centers of total serum IgM and with more intensity than non-gelling. No structural characteristics mattered in ameliorating C5 cleavage by plasmin in extrinsic protease complement activation, but λ/μ/ν- and κ/β-carrageenans almost completely inhibited C5 cleavage. Thus, galactans participated in cell surface biology by imitating surface glycans in inhibition of C3 binding and mannose binding lectin, but as to the tthe heclassical pathway these substances stimulated complement, probably due to their structure based on carrabiose. © 2020 Elsevier Lt
Catalytic antibodies in the bone marrow and other organs of Th mice during spontaneous development of experimental autoimmune encephalomyelitis associated with cell differentiation
No full textExact mechanisms of autoimmune disease development are still yet unknown. However, it is known that the development of autoimmune diseases is associated with defects in the immune system, namely, the violation of the bone marrow hematopoietic stem cells (HSCs) differentiation profiles. Different characteristics of autoimmune reaction development in experimental autoimmune encephalomyelitis (EAE) prone Th mice characterizing T-lymphocytes response were analyzed using standard approaches. Profiles of several HSCs differentiation of bone marrow (BFU-E, CFU-E, CFU-GM, CFU-GEMM, T- and B-lymphocytes) of Th male and female mice during spontaneous development of EAE were noticeably different. Patterns of total lymphocytes, B- and T-cells proliferation in several different organs (bone marrow, blood, spleen, thymus, and lymph nodes) were also remarkably different. In addition, there were in time noticeable differences in their changes for some organs of male and female mice. Characters of changes in the profiles of CD4 and CD8 cells proliferation in some organs not always coincide with those for total T lymphocytes. The changes in the differentiation profiles of HSCs and the level of lymphocytes proliferation in the bone marrow and other organs were associated with the increase in the concentration of antibodies against DNA, myelin basic protein, and myelin oligodendrocyte glycoprotein, and catalytic antibodies hydrolyzing these substrates. Despite some differences in changes in the analyzed parameters, in general, the spontaneous development of EAE in male and female mice occurs to some extent in a comparable way. © 2021, The Author(s)
Oncological care for the patients with hepatocellular carcinoma in COVID-19 pandemic
No full textOn April 27, 2020, COVID-19 pandemic affected more than 2, 5 million of people in more than 200 countries and caused 185 000 deaths. Healthcare systems have come under enormous stress. In COVID-19 pandemic oncological patients face two serious challenges: the risk of severe infectious disease course and the risk of malignant tumor progression. Forced correction of existing oncological standards of care is based on expert and professional community opinions, and daily gaining experience. The issue resumes the data on COVID-19 influence on liver function among the patients with chronic liver diseases and hepatocellular carcinoma. The guidance on HCC management in COVID-19 pandemic are provided. More than 1, 5 million of people suffers from the liver pathology caused by chronic virus hepatitis, alcohol consumption, nonalcoholic fatty liver disease. Mild COVID-19 is often followed by transient liver function disorder which do not need specific treatment. Severe COVID-19 lids to the increase of aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), to the decrease of serum albumin in most cases. Regarding the HCC treatment preference should be given to telemedicine, limitation of contacts in health-care facilities, outpatient treatment, including oral medication (tyrosine kinase inhibitors), and if possible delay of invasive procedures with the help of bridge-therapy and active monitoring. Selecting the patients for surgery, ablation or transarterial chemoembolization (TACE) patients with minimal risk of decompensation, with maximum treatment benefit (on the base of prognostic scales), with lack of comorbid should be preferred. Selective and super selective TACE with drug-eluting beads or radioembolization should be used to reduce the risk of immunosuppression and postembolic syndrome. Live organ transplantation should be considered to be postponed. Targeted therapy could be a temporarily alternative to invasive procedures. © 2020, Remedium Group Ltd. All rights reserved
Characteristics of the herd immunity to SARS-CoV-2 in residents of the saratov region under COVID-19 epidemic [характериСтика популяционного иммунитета к SARS-CoV-2 у жителей Саратова и СаратовСкой оБлаСти в период эпидемии COVID-19]
No full textThe global community is experiencing one of the largest infectious disease outbreaks in the 21st century. In the Saratov Region, the first case of new coronavirus infection was confirmed on March 19, 2020.The maximum increase in cases was noted between May 15 and June 30, during that time the total number of infected people in the region increased from 1526 to 6444. Since July 2020, a stable incidence level of new coronavirus infection has been observed in the Saratov Region, without a steady decline. The aim of the study was to assess the status of population immunity to the SARS-CoV-2 virus among residents of Saratov and the Saratov Region under the COVID-19 epidemic. Materials and methods. In the period from June 23 to July 26, 2020, a serological study of blood samples from 3372 volunteers of different age groups was conducted. The content of antibodies to SARS-CoV-2 was determined by ELISA using a set of reagents “ELISA anti-SARS-CoV-2 IgG” produced by the State Scientific Center of Applied Microbiology and Biotechnology of the Rospotrebnadzor (Russia). Results and discussion. In general, the incidence of COVID-19 in the Saratov Region is taking place against the background of moderate seroprevalence to the SARS-CoV-2 virus, accompanied by a high incidence of non-apparent (asymptomatic) forms of the infectious process. The absence of clinical symptoms of the disease, in the context of the limited use of methods for determining the RNA of the SARS-CoV-2 virus in PCR (11 % of the region’s population) makes it difficult to assess the real spread of the virus in the population and to establish the timing of the formation of persistent herd immunity. A low rate of antibody response among individuals with a positive result of PCR analysis, as well as among volunteers who had an infection in May, June 2020, indicates a weak formation of the immune response, or the prevalence of individuals reacting mainly by activating the cellular link of the immune system in the population. The obtained results, although they need to be explained in a number of respects, can be applied to the organization of preventive measures, including vaccination, in the region. © 2020 Russian Research Anti-Plague Institute. All rights reserved
Peptides contained in the composition of Laennec that contribute to the treatment of hyperferritinemia and iron overload disorders [Пептиды в составе препарата Лаеннек, способствующие устранению гиперферритинемии и перегрузки железом]
No full textIntroduction. Hemosiderosis is a pathologic condition that accompanies liver, lung, and other organ diseases. Polypeptide-containing drug Laennec contributes to the elimination of excessive iron deposits in tissues. Aim. The study was aimed to identify peptides contained in the composition of the drug that take part in the regulation of iron homeostasis and correction of hemosiderosis and hyperferritinemia. Materials and Methods. The study of the drug composition was conducted with hybrid mass-spectrometry and modern methods of analysis of Big Data based on the topological approach to recognition. Results. The preparation contains 19 peptides that are potentially important for the regulation of iron homeostasis. These peptides help to treat the disorders of iron metabolism by regulating the levels of the main hormone of iron homeostasis hepcidin by reducing the synthesis of ferritin and by exhibiting anti-inflammatory and immunomodulatory effects. Conclusion. The identified peptides allowed the authors to describe the molecular mechanisms of the iron overload elimination that are known from experimental and clinical studies of the analyzed polypeptide drug. © 2018 Slovenske Divadlo
Vaccines against covid-19: The comparative estimates of risks in adenovirus vectors
No full textRelevance. The vaccine against the SARS-Cov-2 coronavirus is considered as the most promising approach to curb (tame) a current pandemic and prevent new one. Three vaccines (AstraZeneca’s СhAdOx1 nCov-19, CanSino’s vaccine and Russia’s Sputnik V one) are in Phase III clinical trials and have the S protein as immunogen but different adenovirus vectors. It is known adverse neurological events associated with the СhAdOx1 nCov-19 vacсine. Aim is to investigate the distribution of homologous sequences of adenovirus proteins in human nervous and immune systems proteins, estimate potential risks of using adenovirus vectors in vaccines and discuss possible mechanisms inducing immune damage in the nervous system. Materials and methods. For the computer analysis of peptide (immune epitope) relationship between adenovirus structural proteins and human proteins, the search of homologous sequences was made. All protein sequences were used from databases available on the INTERNET. Results. Among adenoviruses (НАд5, НАд26, ChАдY25, and SAd3) ChАдY25 has the highest content of sequences homologous to human nervous system proteins that may be the cause of autoimmune complications in vaccination. Conclusion: In AstraZeneca’s СhAdOx1 nCov-19 vaccine there are a large number of peptide sequences homologous to human nervous system proteins and it allows to predict the possible risks with this vaccine. © 2020, Numikom. All rights reserved
Epidemiological situation on COVID-19 in Irkutsk Region and forecast for its spread [эпидемиологичеСкая Ситуация по COVID-19 в иркутСкой оБлаСти и прогноЗ ее раСпроСтранения]
No full textAssessment of a particular territory by its epidemiological significance is very relevant in the light of widespread occurrence of new coronavirus infection, COVID-19, in the Russian Federation. Objective. Detection of the epidemiological features and revealing trends in the epidemic process of new coronavirus infection in the Irkutsk Region and forecasting of its spread. Materials and methods. An operational analysis of the epidemiological situation on COVID-19 in the Irkutsk Region as of August 16, 2020 was performed. Restrictive measures were substantiated based on the calculation of the infection spread rate (Rt). Results and discussion. Irkutsk Region remained one of the adverse territories as regards human COVID-19 incidence in the Siberian Federal District and the Russian Federation as of August 16, 2020. The gradual dynamics of the epidemic process was revealed: at the first stage of the epidemic development it was facilitated by the imported cases from affected countries and regions of the Russian Federation, and subsequently by local transmission. The incidence increase was registered 2 months later than in central regions of the Russian Federation. Currently there is a consistent downward trend. The increase in the cases prevailed among rotation workers staying for shift and seasonal activities in the administrative center and northern districts of the Irkutsk Region. The epidemic pattern was determined by gender, age and social characteristics. It is demonstrated that the risk of the new coronavirus infection is determined by the intensity of contacts in family foci, the spread of infection in medical organizations and a significant proportion of asymptomatic carriers. High lethality rates (0.7 %) and mortality rates (31.1 o/oooo) were established among persons over 65 years. The stationary time series observed since June for changing the Rt-indicator with fluctuations ranging from 0.92 to 1.01 requires maintaining control of restrictive measures with prompt management decisions making based on the evolving epidemiological situation in the Irkutsk Region and taking into account the assessment of its possible complication risks. © 2020 Russian Research Anti-Plague Institute. All rights reserved