Training and competitive periods can temporarily impair the performance of an athlete. This disruption can be short- or long-term, lasting up to several days. We analyzed the health indicators of ...3661 athletes during an in-depth medical examination. At the time of inclusion in the study, the athletes were healthy. Instrumental examinations (fluorography, ultrasound examination of the abdominal cavity and pelvic organs, echocardiography, electrocardiography, and stress testing “to failure”), laboratory examinations (general urinalysis and biochemical and general clinical blood analysis), and examinations by specialists (ophthalmologist, otolaryngologist, surgeon, cardiologist, neurologist, dentist, gynecologist (women), endocrinologist, and therapist) were performed. This study analyzed the significance of determining the indicators involved in the implementation of the “catabolism” and “anabolism” phenotypes using the random forest and multinomial logistic regression machine learning methods. The use of decision forest and multinomial regression models made it possible to identify the most significant indicators of blood and urine biochemistry for the analysis of phenotypes as a characterization of the effectiveness of recovery processes in the post-competitive period in athletes. We found that the parameters of muscle metabolism, such as aspartate aminotransferase, creatine kinase, lactate dehydrogenase, and alanine aminotransferase levels, and the parameters of the ornithine cycle, such as creatinine, urea acid, and urea levels, made the most significant contribution to the classification of two types of metabolism: catabolism and anabolism.
In this study, we analyze the occurrence of the unique structural motif, the 3β-corner, belonging to the Structural Classification of Proteins (SCOP) folds, in proteins of various origins. We further ...assess the structural and functional role of this motif as well as the clustering of the biological functions of proteins in which it occurs. It has been shown previously that the 3β-corner occurs with different probabilities in all beta proteins, alpha and beta proteins (α + β and α/β), and alpha classes occur most often in the composition of β-proteins. The 3β-corner is often found as a building block in protein structures, such as β-barrels, -sandwiches, and -sheets/-layers.
The study is devoted to the creation of a dataset of protein structural motifs of the 3β-corner type. The relevance and importance of creating a dataset of 3β-corners is determined by the fact that ...this structure can be an embryo or a ready-made structural block in the process of protein folding, and can also act as an independent object of research in the field of structural biology. The dataset also contains 3β-corner-like structures that are geometrically similar to 3β-corners. The dataset consists of 45,896 structures. For each motif, its characteristics are presented: the name of the protein in which the 3β-corner is recognized, the method and resolution of the protein structure, the coordinates of localization in the protein, the secondary structure of the amino acid sequence, the gyration radius, the solvent-accessible area, and the composition of the elements of the secondary structure. The dataset will allow a comprehensive study of structures on a large scale and advance the understanding of the features and patterns of their structural organization.
Respiratory syncytial virus (RSV) causes severe pathology of the lower respiratory tract in infants, immunocompromised people, and elderly. Despite decades of research, there is no licensed vaccine ...against RSV, and many therapeutic drugs are still under development. Detailed understanding of molecular and cellular mechanisms of the RSV infection pathology can accelerate the development of efficacious treatment. Current studies on the RSV pathogenesis are based on the analysis of biopsies from the infected patients; however deeper understanding of molecular and cellular mechanisms of the RSV pathology could be achieved using animal models. Mice are the most often used model for RSV infection because they exhibit manifestations similar to those observed in humans (bronchial obstruction, mucous hypersecretion, and pulmonary inflammation mediated by lymphocytes, macrophages, and neutrophils). Additionally, the use of mice is economically feasible, and many molecular tools are available for studying RSV infection pathogenesis at the molecular and cellular levels. This review summarizes new data on the pathogenesis of RSV infection obtained in mouse models, which demonstrated the role of T cells in both the antiviral defense and the development of lung immunopathology. T cells not only eliminate the infected cells, but also produce significant amounts of the proinflammatory cytokines TNFα and IFNγ. Recently, a new subset of tissue-resident memory T cells (T
RM
) was identified that provide a strong antiviral defense without induction of lung immunopathology. These cells accumulate in the lungs after local rather than systemic administration of RSV antigens, which suggests new approaches to vaccination. The studies in mouse models have revealed a minor role of interferons in the anti-RSV protection, as RSV possesses mechanisms to escape the antiviral action of type I and III interferons, which may explain the low efficacy of interferon-containing drugs. Using knockout mice, a significant breakthrough has been achieved in understanding the role of many pro-inflammatory cytokines in lung immunopathology. It was found that in addition to TNFα and IFNγ, the cytokines IL-4, IL-5, IL-13, IL-17A, IL-33, and TSLP mediate the major manifestations of the RSV pathogenesis, such as bronchial obstruction, mucus hyperproduction, and lung infiltration by pro-inflammatory cells, while IL-6, IL-10, and IL-27 exhibit the anti-inflammatory effect. Despite significant differences between the mouse and human immune systems, mouse models have made a significant contribution to the understanding of molecular and cellular mechanisms of the pathology of human RSV infection.
Background
First vaccines for prevention of Coronavirus disease 2019 (COVID‐19) are becoming available but there is a huge and unmet need for specific forms of treatment. In this study we aimed to ...evaluate the anti‐SARS‐CoV‐2 effect of siRNA both in vitro and in vivo.
Methods
To identify the most effective molecule out of a panel of 15 in silico designed siRNAs, an in vitro screening system based on vectors expressing SARS‐CoV‐2 genes fused with the firefly luciferase reporter gene and SARS‐CoV‐2‐infected cells was used. The most potent siRNA, siR‐7, was modified by Locked nucleic acids (LNAs) to obtain siR‐7‐EM with increased stability and was formulated with the peptide dendrimer KK‐46 for enhancing cellular uptake to allow topical application by inhalation of the final formulation – siR‐7‐EM/KK‐46. Using the Syrian Hamster model for SARS‐CoV‐2 infection the antiviral capacity of siR‐7‐EM/KK‐46 complex was evaluated.
Results
We identified the siRNA, siR‐7, targeting SARS‐CoV‐2 RNA‐dependent RNA polymerase (RdRp) as the most efficient siRNA inhibiting viral replication in vitro. Moreover, we showed that LNA‐modification and complexation with the designed peptide dendrimer enhanced the antiviral capacity of siR‐7 in vitro. We demonstrated significant reduction of virus titer and lung inflammation in animals exposed to inhalation of siR‐7‐EM/KK‐46 in vivo.
Conclusions
Thus, we developed a therapeutic strategy for COVID‐19 based on inhalation of a modified siRNA‐peptide dendrimer formulation. The developed medication is intended for inhalation treatment of COVID‐19 patients.
siR‐7, targeting SARS‐CoV‐2 RdRp inhibits viral replication in vitro. LNA‐modification and complexation with peptide dendrimer KK‐46 enhanced the antiviral capacity of siR‐7 in vitro. Inhalation exposure of SARS‐CoV‐2‐infected Syrian Hamsters with siR‐7‐EM/KK‐46 reduces the virus titer and lung inflammation.
Abbreviations: GFP, green fluorescent protein; LNA, locked nucleic acid; LUC, luciferase; RISC, RNA‐induced silencing complex; RdRp, RNA‐dependent RNA polymerase; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; siRNA, small interfering RNA; siR‐7‐EM, LNA‐modified small interfering RNA‐7
Biological activity regulation by protein post-translational modification (PTM) is critical for cell function, development, differentiation, and survival. Dysregulation of PTM proteins is present in ...various pathological conditions, including rheumatoid arthritis (RA). RA is a systemic autoimmune disease that primarily affects joints, and there are three main types of protein PTMs associated with the development of this disease, namely, glycosylation, citrullination, and carbamylation. Glycosylation is important for the processing and presentation of antigen fragments on the cell surface and can modulate immunoglobulin activity. The citrullination of autoantigens is closely associated with RA, as evidenced by the presence of antibodies specific to citrullinated proteins in the serum of patients. Carbamylation and dysregulation have recently been associated with RA development in humans.In this study, we performed an overview analysis of proteins with post-translational modifications associated with the development of RA adverted in peer-reviewed scientific papers for the past 20 years. As a result of the search, a list of target proteins and corresponding amino acid sequences with PTM in RA was formed. Structural characteristics of the listed modified proteins were extracted from the Protein Data Bank. Then, molecular dynamics experiments of intact protein structures and corresponding structures with PTMs were performed regarding structures in the list announced in the ProtDB service. This study aimed to conduct a molecular dynamics study of intact proteins and proteins, including post-translational modification and protein citrullination, likely associated with RA development. We observed another exhibition of the fundamental physics concept, symmetry, at the submolecular level, unveiled as the autonomous repetitions of outside the protein structural motif performance globule corresponding to those in the whole protein molecule.
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