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Due to the developing resistance and intolerance to antiretroviral drugs, there is an urgent demand for alternative agents that can suppress the viral load in people living with human immunodeficiency virus (HIV). Recently, there has been increased interest in agents of marine origin such as, in particular, fucoidans to suppress HIV replication. In the present study, the anti-HIV-1 activity of fucoidans from the brown algae Alaria marginata, Alaria ochotensis, Laminaria longipes, Saccharina cichorioides, Saccharina gurianovae, and Tauya basicrassa was studied in vitro. The studied compounds were found to be able to inhibit HIV-1 replication at different stages of the virus life cycle. Herewith, all fucoidans exhibited significant antiviral activity by affecting the early stages of the virus–cell interaction. The fucoidan from Saccharina cichorioides showed the highest virus-inhibitory activity by blocking the virus’ attachment to and entry into the host’s cell, with a selectivity index (SI) > 160.

Background. Atopic dermatitis is an inflammatory skin disease characterized by recurrent lesions and intense pruritus. Nowadays there is a stepwise approach to the treatment of atopic dermatitis, which is defined by disease intensity and complications such as secondary skin infections. However, the current management of atopic dermatitis may not always lead to the expected outcome due to not only immune dysregulation of both adaptive and innate immunity but also imbalance of the skin microbiome. Aims. The aim of the study was to evaluate changes in the composition of the skin microbiome in both lesional and non-lesional skin in patients with atopic dermatitis during standard treatment. Materials and methods. Twenty patients with atopic dermatitis and twenty six healthy controls over 18 years old were included into the study. All microbiome samples were obtained from lesional and non-lesional skin sites of atopic dermatitis patients before and after therapy. Whereas samples from healthy controls were taken once from a flexor surface of the elbow. Species identification of clinical isolates were identified using MALDI Biotyper Sirius (Bruker Daltonics). Results. At baseline, the prevalence of S. aureus colonization among patients with atopic dermatitis was 34.20% in lesional skin and 32.50% in non-lesional skin. After treatment, there was a significant decrease in the prevalence of S. aureus carriage in both lesional and non-lesional skin areas (р 0.05). However, no significant difference was observed in the proportion of all other staphylococci (р 0.1). Interestingly, S. aureus was not found in healthy controls. Conclusions. The results of the study demonstrated the effectiveness of standard therapy for managing patients with atopic dermatitis as it had a positive impact on the skin microbial community and showed a decrease in S. aureus proportion after the treatment.

Introduction. Influenza is one of the most pressing global health problems. Despite the wide range of available anti-influenza drugs, the viral drug resistance is an increasing concern and requires the search for new approaches to overcome it. A promising solution is the development of drugs with action that is based on the inhibition of the activity of cellular genes through RNA interference. Aim. Evaluation in vivo of the preventive potential of miRNAs directed to the cellular genes FLT4, Nup98 and Nup205 against influenza infection. Materials and methods. The A/California/7/09 strain of influenza virus (H1N1) and BALB/c mice were used in the study. The administration of siRNA and experimental infection of animals were performed intranasally. The results of the experiment were analyzed using molecular genetic and virological methods. Results. The use of siRNA complexes Nup98.1 and Nup205.1 led to a significant decrease in viral reproduction and concentration of viral RNA on the 3rd day after infection. When two siRNA complexes (Nup98.1 and Nup205.1) were administered simultaneously, a significant decrease in viral titer and concentration of viral RNA was also noted compared with the control groups. Conclusions. The use of siRNAs in vivo can lead to an antiviral effect when the activity of single or several cellular genes is suppressed. The results indicate that the use of siRNAs targeting the cellular genes whose expression products are involved in viral reproduction is one of the promising methods for the prevention and treatment of not only influenza, but also other respiratory infections.

Some microorganisms can develop tolerance. On the one hand, it allows pathogenic microbes to escape immune surveillance, on the other hand, it provides the possibility to microbiota representatives to colonize different biotopes and build a symbiotic relationship with the host. Complex regulatory interactions between innate and adaptive immune systems as well as stimulation by antigens help microbes control and maintain immunological tolerance. An important role in this process belongs to innate immune cells, which recognize microbial components through pattern-recognition receptors. Toll-like receptors (TLRs) represent the main class of these receptors. Despite the universality of the activated signaling pathways, different cellular responses are induced by interaction of TLRs with microbiota representatives and pathogenic microbes, and they vary during acute and chronic infection. The research on mechanisms underlying the development of TLR tolerance is significant, as the above receptors are involved in a wide range of infectious and noninfectious diseases; they also play an important role in development of allergic diseases, autoimmune diseases, and cancers. The knowledge of TLR tolerance mechanisms can be critically important for development of TLR ligand-based therapeutic agents for treatment and prevention of multiple diseases.

The human immunodeficiency virus (HIV) is currently one of the most pressing global health problems. Since its discovery in 1978, HIV has claimed the lives of more than 35 million people, and the number of people infected today reaches 37 million. In the absence of highly active antiretroviral therapy (HAART), HIV infection is characterized by a steady decrease in the number of CD4+ T-lymphocytes, but its manifestations can affect the central nervous, cardiovascular, digestive, endocrine and genitourinary systems. At the same time, complications induced by representatives of pathogenic and opportunistic microflora, which can lead to the development of bacterial, fungal and viral concomitant infections, are of particular danger. It should be borne in mind that an important problem is the emergence of viruses resistant to standard therapy, as well as the toxicity of the drugs themselves for the body. In the context of this review, of particular interest is the assessment of the prospects for the creation and clinical use of drugs based on small interfering RNAs aimed at suppressing the reproduction of HIV, taking into account the experience of similar studies conducted earlier. RNA interference is a cascade of regulatory reactions in eukaryotic cells, which results in the degradation of foreign messenger RNA. The development of drugs based on the mechanism of RNA interference will overcome the problem of viral resistance. Along with this, this technology makes it possible to quickly respond to outbreaks of new viral diseases.

The contribution of the antimicrobial activity of sIgA, lactoferrin, -lactalbumin, serum albumin, and lysozyme to the total antimicrobial activity of whey was evaluated. 66 breast milk samples from healthy women aged from 23 to 45 years collected at different periods of lactation were studied. It was found that along with proceeding the lactation period, not only the total antimicrobial activity (r = 0.944) decreased, but also the activity of the low molecular weight fraction containing the sum of antimicrobial peptides (r = 0.950). The median lactoferrin level varied from 3.46 mg/ml in colostrum down to 0.94 mg/ml one year after the onset of lactation that correlated with whey activity (r = 0.616). The concentration of sIgA was peaked in the whey of colostrum (5.01 mg/ml) and significantly reduced in mature milk, remaining approximately at the same level in subsequent periods of lactation (1.0 mg/ml). Serum albumin concentration significantly decreased while proceeding through lactation period (from 5.52 to 4.68 mg/ml) and correlated with whey activity (r = 0.589). Evaluating effects of the purified -lactalbumin on C. albicans cells within the range of 520 mg/ml by spectrophotometry and microscopy showed the absence of fungicidal activity. At the same time, purified lactoferrin, IgA, lysozyme, and serum albumin demonstrated a direct fungicidal effect. The activity of the IgA preparation at a concentration relevant to the sIgA content in the whey of the first day colostrum was 50.0%, and in the whey after 12 months 31.0%; lactoferrin 26.7% and 3.4%; serum albumin 15.0% and 17.7%; lysozyme 0.1% and 1.8%. Thus, the sum of the activities of these polypeptides at concentrations typical for the first-day colostrum was 91.7%, which is comparable to the total activity of this whey 82.4%. The sum of the activities of these polypeptides, typical for 12 months of lactation, was 53.9%, and the total whey activity relevant to this period was 64.5%. Therefore, IgA and lactoferrin contribute the most significant antimicrobial activity in the whey of colostrum, whereas after 12 month-breastfeeding IgA and serum albumin become most significant.

Aim. To study the inhalation of an active form of hydrogen effect to mucosal and system immunity in a rehabilitation program for health workers. Materials and methods. The study involved patients that survived COVID-19 after therapy with inhaled hydrogen for 90 minutes (n=30), and a control group of patients treated according to standard protocol for managing patients that survived COVID-19 during the rehabilitation period (n=30). Biomaterial was carried out in 2 stages: on the first day of the study, before the accepted therapy and on the 10th day of the study. The indicators of humoral and cellular immunity were studied. The levels of secretory immunoglobulin A (sIgA) and IgG were investigated using the method of enzyme-linked immunosorbent assay. Phagocytosis was assessed on a Beckman Coulter FC-500 flow cytometer. Statistical data processing was carried out in the GraphPad Prism 7.00 software using nonparametric methods. Results. It was shown that the phagocytic index (PI) of monocytes in nasal scrapings after inhaled hydrogen treatment did not significantly change relative to the first day of treatment and control, while the PI of granulocytes in nasal scrapings significantly increased relative to the first day by 2.5 times (p=0.000189), as well as relative to the control by 1.1 times (p=0.047410). PI of monocytes in pharyngeal scrapings showed a significant increase relative to the first day of treatment by 2.8 times (p=0.041103), however, did not differ relative to the control. PI of granulocytes of pharyngeal scraping did not differ significantly relative to the first day and control. PI of granulocytes and blood monocytes of the studied group did not change significantly. PI of granulocytes and monocytes of peripheral blood relative to control during therapy did not change. The sIgA level in nasal scrapings significantly increased by 2.9 times, while in pharyngeal scrapings the level of sIgA significantly decreased by 2 times. Сonclusion. We have shown an increase in granulocytes PI in the nasal cavity and oral monocytes, as well as in the level of sIgA in the nasal cavity during therapy with active hydrogen. The data obtained indicate the effectiveness of therapy, which can be used both in the treatment of COVID-19, and in post-COVID syndrome as an additional therapy. The absence of changes in blood parameters, as well as individual links in nasal and pharyngeal scrapings, requires further study to develop ways to overcome treatment tolerance.

In surgical dentistry, suture material is the only foreign body that remains in the tissues after surgery, and it can lead to several negative reactions, for example, infection of the wound. The purpose of this study was to compare the mechanical properties and microbiological resistance of mono- and polyfilament suture materials used in tooth extraction operations. The study of elongation and knot force was carried out on an Instron 5969 Dual Column Testing System device. The capillarity of the materials was studied on a setup assembled by the authors manually by immersing the ends of the filaments in a colored manganese solution. A microbiological study was carried out on the threads taken for the experiment immediately after wound suturing, and on day 7, at which time they were removed. The comparison was made according to Rothia mucilaginosa, Streptococcus sanguinis, Staphylococcus epidermidis. Results: monofilament suture materials (Prolene and Glycolon), after calculating the Kruskal–Wallis and Mann–Whitney indices, showed better performance in all experiments compared to polyfilament sutures (Vicryl and PGA). In capillarity comparison, there was a significant difference between groups (p = 0.00018). According to the sum of the results of three microbiological studies on day 7, monofilament suture materials absorbed less of the studied bacteria on their surface compared to the polyfilament ones (p < 0.05). Conclusions: Of the studied suture materials, Prolene had the best microbiological resistance and good mechanical properties.

Glioblastoma multiforme (GBM) accounts for almost half of all primary malignant brain tumors in adults and has a poor prognosis. Here we demonstrated the oncolytic potential of the L-16 vaccine strain of measles virus (MV) against primary human GBM cells and characterized the genetic patterns that determine the sensitivity of primary human GBM cells to oncolytic therapy. MV replicated in all GBM cells, and seven out of eight cell lines underwent complete or partial oncolysis. RNA-Seq analysis identified about 1200 differentially expressed genes (FDR < 0.05) with at least two-fold expression level change between MV-infected and uninfected cells. Among them, the most significant upregulation was observed for interferon response, apoptosis and cytokine signaling. One out of eight GBM cell lines was defective in type I interferon production and, thus, in the post-interferon response, other cells lacked expression of different cellular defense factors. Thus, none of the cell lines displayed induction of the total gene set necessary for effective inhibition of MV replication. In the resistant cells, we detected aberrant expression of metalloproteinase genes, particularly MMP3. Thus, such genes could be considered intriguing candidates for further study of factors responsible for cell sensitivity and resistance to L-16 MV infection.

Influenza virus infections pre-dispose an individual to secondary pneumococcal infections, which represent a serious public health concern. Matching influenza vaccination was demonstrated helpful in preventing postinfluenza bacterial infections and associated illnesses in humans. Yet, the impact of influenza hemagglutinin (HA)-specific immunity alone in this dual-infection scenario remains elusive. In the present study, we assessed the protective effect of neutralizing and non-neutralizing anti-hemagglutinin immunity in a BALB/c influenza-pneumococcus superinfection model. Our immunogens were insect cell-expressed hemagglutinin-Gag virus-like particles that had been differentially-treated for the inactivation of bioprocess-related baculovirus impurities. We evaluated the potential of several formulations to restrain the primary infection with vaccine-matched or -mismatched influenza strains and secondary bacterial replication. In addition, we investigated the effect of anti-HA immunity on the interferon status in mouse lungs prior to bacterial challenge. In our experimental setup, neutralizing anti-HA immunity provided significant but incomplete protection from postinfluenza bacterial superinfection, despite effective control of viral replication. In view of this, it was surprising to observe a survival advantage with non-neutralizing adaptive immunity when using a heterologous viral challenge strain. Our findings suggest that both neutralizing and non-neutralizing anti-HA immunity can reduce disease and mortality caused by postinfluenza pneumococcal infections.