Kinetics of interferon-λ and receptor expression in response to in vitro respiratory viral infection.

The major protective immune response against viruses is the production of type I and III interferons (IFNs). IFNs induce the expression of hundreds of IFN-stimulated genes (ISGs) that block viral replication and further viral spread. In this report, we analyzed the expression of IFNs and some ISGs (MxA, PKR, OAS-1, IFIT-1, RIG-1, MDA5, SOCS-1) in alveolar epithelial cells (A549) in response to infection with influenza A viruses (A/California/07/09 (H1N1pdm); A/Texas/50/12 (H3N2)); influenza B virus (B/Phuket/3073/13); adenovirus type 5 and 6; or respiratory syncytial virus (strain A2).

Properties of recombinant extracellular N-terminal domain of human high-affinity copper transporter 1 (hNdCTR1) and its interactions with Cu(II) and Ag(I) ions.

High-affinity copper transporter 1 (CTR1) is a key link in the transfer of copper (Cu) from the extracellular environment to the cell. Violation in the control system of its expression, or mutations in this gene, cause a global copper imbalance. However, the mechanism of copper transfer CTR1 remains unclear.

Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells.

The design of cationic liposomes for efficient mRNA delivery can significantly improve mRNA-based therapies. Lipoplexes based on polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) were formulated in different molar ratios (1:1, 1:2, 1:3) to efficiently deliver model mRNAs to BHK-21 and A549. The objective of this study was to examine the effect of 2X3-DOPE composition as well as lipid-to-mRNA ratio (amino-to-phosphate group ratio, N/P) on mRNA transfection.

Peripheral Blood Mononuclear Cell Cytokine mRNA Profiles in Acute Respiratory Infection Patients.

Introduction: Respiratory infections, collectively, are one of the World's most common and serious illness groups. As recent observations have shown, the most severe courses of acute respiratory infection, often leading to death, are due to uncontrolled cytokine production (hypercytokinemia).

Methods: The study involved 364 patients with respiratory illness being treated in clinics in St.

Exosomes Released by Influenza-Virus-Infected Cells Carry Factors Capable of Suppressing Immune Defense Genes in Naïve Cells.

Exosomes are involved in intercellular communication and can transfer regulatory molecules between cells. Consequently, they can participate in host immune response regulation. For the influenza A virus (IAV), there is very limited information on changes in exosome composition during cell infection shedding light on the potential role of these extracellular membrane vesicles.

Simultaneous Detection of RIG-1, MDA5, and IFIT-1 Expression Is a Convenient Tool for Evaluation of the Interferon-Mediated Response.

In this study, we developed a novel, multiplex qPCR assay for simultaneous detection of RIG-1, MDA5, and IFIT-1 at the mRNA level. The assay was validated in A549 cells transfected with in vitro transcribed RNAs. Both exogenous RNA-GFP and self-amplifying (saRNA-GFP) induced significant expression of RIG-1, MDA5, IFIT-1, as well as type I and III interferons.

Prospects for the use of graphene-based biological sensors in the early diagnosis of Alzheimer's disease (review of literature).

Among the most significant challenges presented to modern medicine is the problem of cognitive disorders. The relevance of her research is determined by the wide spread of disorders of the higher cortical functions, their significant negative impact on the quality of life of patients, as well as high economic costs on the part of the state and the patient's relatives aimed at organizing medical, diagnostic and rehabilitation processes. The main cause of cognitive impairment in the elderly is Alzheimer's disease.

Investigation of the Morphology and Electrical Properties of Graphene Used in the Development of Biosensors for Detection of Influenza Viruses.

In this study, we discuss the mechanisms behind changes in the conductivity, low-frequency noise, and surface morphology of biosensor chips based on graphene films on SiC substrates during the main stages of the creation of biosensors for detecting influenza viruses. The formation of phenylamine groups and a change in graphene nano-arrangement during functionalization causes an increase in defectiveness and conductivity. Functionalization leads to the formation of large hexagonal honeycomb-like defects up to 500 nm, the concentration of which is affected by the number of bilayer or multilayer inclusions in graphene.

A novel method for multiplex protein biomarker analysis of human serum using quantitative MALDI mass spectrometry.

In this work, we have extended our previously proposed approach for determining protein concentrations in human serum (using MALDI-TOF mass spectrometry) to include simultaneous analysis of several proteins associated with acute inflammation (alpha-2-macroglobulin, fetuin-A, serum amyloid A1). This technique can be used to diagnose systemic inflammation and provides results in 4-5 h. The developed approach was verified using standard immunological methods (ELISA).

IFN-λ1 Displays Various Levels of Antiviral Activity In Vitro in a Select Panel of RNA Viruses.

Type III interferons (lambda IFNs) are a quite new, small family of three closely related cytokines with interferon-like activity. Attention to IFN-λ is mainly focused on direct antiviral activity in which, as with IFN-α, viral genome replication is inhibited without the participation of immune system cells. The heterodimeric receptor for lambda interferons is exposed mainly on epithelial cells, which limits its possible action on other cells, thus reducing the likelihood of developing undesirable side effects compared to type I IFN.

Rosin Derivatives as a Platform for the Antiviral Drug Design.

The increased complexity due to the emergence and rapid spread of new viral infections prompts researchers to search for potential antiviral and protective agents for mucous membranes among various natural objects, for example, plant raw materials, their individual components, as well as the products of their chemical modification. Due to their structure, resin acids are valuable raw materials of natural origin to synthesize various bioactive substances. Therefore, the purpose of this study was to confirm the possibility of using resin acid derivatives for the drug design.

Quench me if you can: Alpha-2-macroglobulin trypsin complexes enable serum biomarker analysis by MALDI mass spectrometry.

One of the main functions of alpha-2-macroglobulin (A2M) in human blood serum is the binding of all classes of protease. It is known that trypsin, after such interaction, possesses modified proteolytic activity. Trypsin first hydrolyzes two bonds in A2M's 'bait region', and the peptide VGFYESDVMGR is released from A2M.

Graphene on SiC Substrate as Biosensor: Theoretical Background, Preparation, and Characterization.

This work is devoted to the development and optimization of the parameters of graphene-based sensors. The graphene films used in the present study were grown on semi-insulating 6H-SiC substrates by thermal decomposition of SiC at the temperature of ~1700 °C. The results of measurements by Auger and Raman spectroscopies confirmed the presence of single-layer graphene on the silicon carbide surface.

The Key Roles of Interferon Lambda in Human Molecular Defense against Respiratory Viral Infections.

Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (, , ), and they have immuno-modulatory activities that shape adaptive immune responses.

Meglumine acridone acetate, the ionic salt of CMA and N-methylglucamine, induces apoptosis in human PBMCs via the mitochondrial pathway.

Meglumine acridone acetate (MA) is used in Russia for the treatment of influenza and other acute respiratory viral infections. It was assumed, until recently, that its antiviral effect was associated with its potential ability to induce type I interferon. Advanced studies, however, have shown the failure of 10-carboxymethyl-9-acridanone (CMA) to activate human STING.

Antibody microarray immunoassay for screening and differential diagnosis of upper respiratory tract viral pathogens.

Upper respiratory tract infections are the world's most common infectious disease. The etiologic agents behind upper respiratory tract infections (URTIs) are, in fact, a diverse set of pathogens such as influenza, parainfluenza, adenovirus, rhinovirus, and others. More than 200 pathogens are known to be involved.

Ceftaroline Resistance Selection of Methicillin-Resistant Involves Different Genetic Pathways.

The pathways in the development of ceftaroline resistance of methicillin-resistant (MRSA) isolates belonging to the ST8, ST239, and ST228 were evaluated. Ceftaroline-resistant derivatives were isolated through selection during 40 passages. Ceftaroline MIC measurements and whole-genome sequencing were performed after 5, 20, and 40 passages.

[In vitro Antiviral Activity of Recombinant Antibodies of IgG and IgA Isotypes to Hemagglutinin of the Influenza A Virus].

Seasonal and highly infectious strains of the influenza A and influenza B viruses cause millions of cases of severe complications in elderly people, children, and patients with immune diseases each year. Immunoglobulin A (IgA), which is an active component of humoral immunity, can prevent the spread of the virus in the upper respiratory tract. The preparation and study of the properties of recombinant virus-specific IgA could be an important approach to finding new means of preventing and treating influenza.

COMPARISON OF INFLUENZA A VIRUS INHIBITION IN VITRO BY SIRNA COMPLEXES WITH CHITOSAN DERIVATIVES, POLYETHYLENEIMINE AND HYBRID POLYARGININE-INORGANIC MICROCAPSULES.

Anti-influenza drugs and vaccines have a limited effect due to the high mutation rate of virus genome. The direct impact on the conservative virus genome regions should significantly improve therapeutic effectiveness. The RNA interference mechanism (RNAi) is one of the modern approaches used to solve this problem.

EVOLUTIONARY DYNAMICS OF STRUCTURAL AND FUNCTIONAL DOMAINS OF INFLUENZA A VIRUS NS1 PROTEIN.

Influenza A virus (IAV) NS1 protein is one of the key viral factors responsible for virus-host interactions. NS1 counteracts host antiviral defense, participates in the processing and export of cellular mRNAs, regulates the activity of viral RNA polymerase and the expression of viral genes, and influences the cellular signaling systems. Multiple NS1 functions are carried out due to the interactions with cellular factors, the number of which exceeds one hundred.

Ceruloplasmin gene expression profile changes in the rat mammary gland during pregnancy, lactation and involution.

Copper metabolism disturbances in mammary gland (MG) cells have severe consequences in newborns. The mechanism that controls the balance of copper in the MG has not been thoroughly characterized. Four primary copper homeostasis genes in mammals: (1) ceruloplasmin (Cp) encoding multifunction multicopper blue (ferr)oxidase; (2) CTR1 encoding high affinity copper importer 1; and (3 and 4) two similar genes encoding Cu(I)/Cu(II)-ATPases P1 type (ATP7A and ATP7B) responsible for copper efflux from the cells and metallation of cuproenzymes formed in the Golgi complex are expressed in MG.

The influenza A virus NS genome segment displays lineage-specific patterns in predicted RNA secondary structure.

Background: Influenza A virus (IAV) is a segmented negative-sense RNA virus that causes seasonal epidemics and periodic pandemics in humans. Two regions (nucleotide positions 82-148 and 497-564) in the positive-sense RNA of the NS segment fold into a multi-branch loop or hairpin structures.

Results: We studied 25,384 NS segment positive-sense RNA unique sequences of human and non-human IAVs in order to predict secondary RNA structures of the 82-148 and 497-564 regions using RNAfold software, and determined their host- and lineage-specific distributions.

Development of a multiplex quantitative PCR assay for the analysis of human cytokine gene expression in influenza A virus-infected cells.

Cytokines are global mediators of cellular communications that are involved in broad array of biological processes, including the immunological and inflammatory mechanisms of virus-host interactions. Measuring the gene expression of simultaneously expressed cytokines is necessary for understanding the pathogenesis of many viral infections, including influenza. We developed a multiplex quantitative real-time PCR (qPCR) method for the detection of the following human cytokines: IL-1B, IL-2, IL-4, IL-6, IL-10, IL-12B, IL-18, IFN-γ and TNF.

Molecular mechanisms enhancing the proteome of influenza A viruses: an overview of recently discovered proteins.

Influenza A virus is one of the major human pathogens. Despite numerous efforts to produce absolutely effective anti-influenza drugs or vaccines, no such agent has been developed yet. One of the main reasons for this complication is the high mutation rate and the specific structure of influenza A viruses genome.