The aim of this study was to investigate the antimicrobial activity of piperazine ring-containing quinazoline compounds against Klebsiella pneumoniae. The study of antimicrobial activity was carried out in vitro via serial dilutions of the pyrimidine compound, with subsequent determination of the minimum inhibitory concentration. Screening for anti-Klebsiella activity was performed against pyrimidine derivatives of quinazolinone with a piperazine ring 1-methyl-3-[2-(4-methylpiperazino)-2-oxoethyl]quinazoline-2,4(1H,3H)-dione (VMA–20–26), 1-methyl-3-[2-(4-phenylpiperazino)-2-oxoethyl]quinazoline-2,4(1H,3H)-dione (VMA–20–27), 1,3-Di[2-(4-methylpiperazin-1yl)-2-oxoethyl]quinazoline-2,4(1H,3H)-dione (VMA–20–29), 1,3-Di[2-(4-phenylpiperazin-1yl)-2-oxoethyl]quinazoline-2,4(1H,3H)-dione (VMA–20–30), 1-Phenacin-3-[2-(4-phenylpiperazino)-2-oxoethyl]quinazoline-2,4(1H,3H)-dione (VMA–20–41), 1-[2-(4-phenylpiperazino-2-oxoethyl]quinazoline-2,4(1H,3H)-dione (VMA–24–04), synthesized by scientists from Volgograd State Medical University. A study of the antimicrobial activity of quinazoline compounds containing a piperazine ring against K. pneumoniae has established that the most active compounds exhibiting bacteriostatic activity at concentrations of 1 and 0.5 µg/ml and bactericidal activity at 4 and 16 µg/ml, comparable to ciprofloxacin, are 1-methyl-3-[2-(4-methylpiperazino)-2-oxoethyl]quinazoline-2,4(1H,3H)-dione (VMA–20–26) and 1-[2-(4-phenylpiperazino-2-oxoethyl]quinazoline-2,4(1H,3H)-dione (VMA–24–04). The obtained results prompt further detailed studies of toxicity and pharmacological activity, including antimicrobial activity, both in vitro and in vivo.

Background. The spread of pathogenic antibiotic-resistant microorganisms often leads to the inefficiency of antimicrobial therapy. One of the solutions to this problem is the search for new active natural antibiotics.

The aim of the study. The search for producers that show antibiotic activity in relation to resistant test microorganisms, including those from the ESKAPE group, in the natural environment. The object of the study was bacteria isolated from a poorly studied environment — the soil of the tropical desert, namely the soil of the Sinai Peninsula.

Methods. Soil suspensions were sown on universal sterling agar environment No. 2 Gause, suitable for the growth of many bacteria and fungi. The isolated microorganisms were identified by morphological characteristics and by the analysis of ribosomal RNA genes. Deep cultivation was carried out in nutrient media of various compositions under aeration conditions. Test strains of gram-positive and gram-negative bacteria, as well as fungi, were used to evaluate antimicrobial activity.

Results. 38 cultures of microorganisms were isolated: 9 strains of fungi, 5 strains of streptomycetes, 2 strains of Bacillus subtilis, and 22 strains of representatives of other taxonomic groups of bacteria. 5 strains of streptomycetes and 2 strains of B. subtilis exhibit antibiotic activity, in particular against resistant pathogens of the ESKAPE group, namely methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, as well as Mycobacterium smegmatis — a preliminary test in the search for anti-tuberculosis drugs.

Conclusion. The search for antibiotic producers from the isolated desert soil was productive, due to the fact that a quarter of the isolated bacterial strains exhibited antimicrobial activity, even against multidrug-resistant test strains. Bio-synthesis conditions have been developed for subsequent isolation and chemical study. The most promising strains are Streptomyces rochei INA 01452 and INA 01509, as well as Streptomyces sp. INA 01523.

Background. Antibiotics were widely used during the COVID-19 pandemic, which may have led to an increase in the number and diversity of antibiotic resistance genes. Most studies assessing the human resistome during this period were conducted over a short period of time and on different cohorts of people. In this case, the most informative approach is to study the composition of the resistome in people who have and have not recovered from COVID-19, using paired stool samples obtained before and after the pandemic.

The aim of the study was to assess the prevalence of antibiotic resistance genes in the intestinal microbiota of the adult population of Arkhangelsk city before and after the COVID-19 pandemic.

Material and Methods. The study included a random population sample of residents of Arkhangelsk who provided paired stool samples at intervals of five years. The study procedure included surveying and identification of antibiotic resistance genes in stool samples using polymerase chain reaction. Processing of the obtained data was carried out in the R language.

Results. The samples of almost all participants contained genes that cause resistance to macrolides: mefA and ermB. The frequency of glycopeptide resistance genes (vanA and vanB) in post-pandemic samples decreased significantly. There is a trend towards an increase in the number of antibiotic resistance genes among patients hospitalized for COVID-19 compared to outpatients. The proportion of macrolide resistance genes shifted toward an increased relative representation of mefA in post-pandemic samples.

Conclusion. The resistome of study participants did not undergo significant changes during the COVID-19 pandemic, except for a decrease in the prevalence of glycopeptide resistance genes and a change in the ratio of macrolide resistance genes.

Background. The search for effective combinations of immune checkpoint inhibitors with common cytostatics, targeted cancer drugs and other treatments is a modern trend to improve the effectiveness of immunotherapy.

Purpose. Development of a panel of lung cancer cell cultures and cells of normal lung tissue with a characterized molecular phenotype by expression of one of the targets of immunotherapy — programmed cell death ligand 1 (PD-L1).

Methods. PD-L1 expression was quantitatively analyzed by immunofluorescence method associated with flow cytometry.

Results. A panel of lung cancer cell cultures of different histotypes and cells of normal lung tissue with characterized molecular phenotype was formed according to the expression of the immunotherapy target PD-L1. In terms of PD-L1 expression intensity, cell cultures can be arranged in a series: Calu-1  HFL-1  Calu-6  Wi-26  A-549  H-596  H-211, with a 7-fold difference in the index between Calu-1 and H-211.

Conclusion. The panel of cultures of cancer and normal lung cells is recommended for the search and development of effective modifiers of the immunotherapy target PD-L1.

Background. It has been established that metalloproteinase-9 (hereinafter MMP-9) is the most inducible enzyme of the metalloproteinase family. It regulates the migration of leukocytes to the site of inflammation, participates in the stimulation of pro- and anti-inflammatory reactions and, thus, can act as an accessible biomarker of pulmonary matrix damage.

The aim of the study was to evaluate MPP-9 levels and their relationship with systemic immunity indicators in the novel coronavirus infection COVID-19 during treatment with various antiviral drugs.

Materials and methods. The study included patients aged 35–69 years (N=25) diagnosed with novel coronavirus infection COVID-19, hospitalized in the Infectious Diseases Inpatient Department of the State Autonomous Healthcare Institution of the Sverdlovsk Region City Clinical Hospital No. 40, Yekaterinburg, who were divided into two groups depending on antiviral therapy: group 1 (N=15) received favipiravir, group 2 (N=10) received riamilovir (trade name Triazavirin ®).

Results. There was a 2-fold reduction in the duration of dyspnea (P<0.05), catarrhal symptoms — by 2.7 times, fever — by 1.3 times (P<0.05) among patients receiving riamilovir compared to patients receiving favipiravir. Against the background of riamilovir therapy, there was a dynamic increase in the level of leukocytes and CD 3+ lymphocytes by 1.9 times (P<0.05) and an increase in the level of MMP-9 by 3 times (P<0.05) compared to the initial indicators. Correlations were found between the level of MMP-9 and a reduction in the duration of the following clinical manifestations: dyspnea (R=0.5, P<0.001), respiratory failure (R=0.4, P<0.001), fever (R=0.4, P<0.001), as well as the level of lymphocytes (R=0.6, P<0.001), CD 4+ and CD 3+ lymphocytes (R=0.6 (P<0.001) and R=0.7 (P<0.001), respectively).

Conclusions. A direct relationship between MMP-9 and clinical manifestations of the novel coronavirus infection COVID-19, as well as indicators of systemic immunity, has been established.

Background. Iron deficiency or iron-deficiency anaemia (IDA) are some of the most common systemic complications of inflammatory bowel diseases (IBD). Symptoms such as fatigue, reduced ability to concentrate, as well as decreased exercise tolerance can mimic common symptoms of IBD and therefore can be easily ignored. Numerous studies have shown that anaemia is a major contributor to reduced quality of life in patients with IBD. However, the correction of anaemia can significantly improve the quality of life of patients with IBD. Therefore, it is recommended that every patient with IBD undergo regular screening for iron deficiency and anaemia. If they are detected, appropriate examination and treatment should be initiated.

The aim of the study was to analyse the causes of IDA and anaemia for chronic conditions in ulcerative colitis patients in Udmurtia.

Material and methods. Clinical protocols, laboratory and instrumental data of 101 patients with ulcerative colitis aged from 18 to 82 years included in the «Republican register of patients with chronic inflammatory bowel diseases» of Udmurtia were analysed.

Results of discussion. Anaemia is the most widespread systemic complication in patients with IBD, which includes ulcerative colitis. In this regard, new and improved methods of diagnosing and treating anaemia in ulcerative colitis are being searched for.

The aim of the study is to assess the efficacy, immunogenicity, and safety of the combined vector vaccine Gam-COVID-Vac and to determine the risk factors for the development of adverse events (AEs) in patients with rheumatic diseases (RD).

Patients and methods. The present study consisted of a retrospective and prospective parts, which included 295 and 42 patients with RD, as well as 113 and 57 healthy controls, respectively. Information about efficacy was obtained from 291 patients with RD and 146 controls, which was assessed by the incidence of PCR-confirmed COVID-19 cases from 31 to 365 days after vaccination. The concentration of antibodies to SARS-CoV-2 was assessed by enzyme immunoassay in a prospective cohort at 1, 3, 6, and 12 months after administration of the second component of the vaccine. Safety was studied in all participants based on the incidence of AEs and exacerbation of underlying RD.

Results. After vaccination, 29 (9.97%) cases of COVID-19 were recorded in patients with RD, 27 of them were mild, and 2 required hospitalization, all cases ended in recovery. Treatment with rituximab before vaccination increased the risk of developing COVID-19 by 2.3 times. A sig-nificant increase in antibody titers was observed after 1, 3, and 12 months after full immunization in patients with RD (P<0.006 for all points). AEs were absent in 40.72% of patients with RD and 24.71% healthy controls, P<0.001. Exacerbations of RD were registered in 2 (0.6%) cases. The risk of developing local and systemic AEs (depending on the administered component) was increased in women, patients under the age of 60 year, with a duration of RD less than 10 years, and methotrexate therapy (P<0.016 for all cases).

Conclusions. According to the data obtained, the use of Gam-COVID-Vac in patients with RD is characterized by good efficacy, sufficient immunogenicity, and safety.

The review presents current treatment regimens for infections associated with carbapenem-resistant Acinetobacter baumannii, which are leading nosocomial pathogens exhibiting multidrug resistance to available antibacterial drugs. To date, widely used beta-lactam antibiotics, including carbapenems, have lost their effectiveness in combating acinetobacter infections, while new antibiotics remain poorly available to patients. Therefore, the only measure to combat the antibiotic resistance of carbapenem-resistant A. baumannii is to evaluate the efficiency of combination therapy in vitro and in vivo, which is of particular interest to Russian and foreign researchers.

To date, in vivo and in vitro experiments, as well as clinical studies, have identified antihyperlipidemic, anti-inflammatory, immunomodulatory, antioxidant, antidiabetic, gastro- and hepatoprotective effects of polysaccharides from various types of algae, which are used for medical purposes as biologically active additives (BAA) to food, due to their biocompatibility, low toxicity (most of them are completely nontoxic), as well as the ability to act simultaneously on many pathogenetic targets in somatic and infectious diseases. The review presents the latest materials on the prospects of using marine polysaccharides for the prevention and treatment of non-alcoholic fatty liver disease (NAFLD), the most common chronic disease of this organ. Experimental data on the ability of algae polysaccharides to modulate insulin sensitivity, increase the activity of β-oxidation of fatty acids, reducing the lipid load in the liver, are summarized. The antioxidant and anti-inflammatory potencies of polysaccharides, as well as their effect on the intestinal microbiota, play a significant role in protecting the liver in NAFLD. Further studies are required to clarify the mechanism of action of brown algae polysaccharides on liver cells, to determine the composition and clinical availability of these compounds in the form of algae products, nutritional supplements, and regulated therapeutics.

To date, preparations containing succinic acid (succinate) are widely known to specialists working in intensive care. Several such preparations have gained wide acclaim among anesthesiologists and resuscitators, namely: Reamberin, infusion solution — a crystalloid preparation containing 1.5% meglumine sodium succinate; Remaxol, infusional solution – a complex infusional solution containing, in addition to succinic acid, nicotinamide, inosine, as well as the aliphatic α-amino acid methionine (which serves in the body as a donor of methyl groups in S-adenosyl-methionine during the biosynthesis of choline, adrenaline, etc., and is also a source of sulfur during the biosynthesis of cysteine); Cytoflavin, a solution for intravenous administration, containing a complex of two vital vitamins necessary to provide a pool of coenzymes — B2 in the form of a highly water-soluble form of riboflavin mononucleotide and PP in the form of nicotinic acid amide, succinic acid, and inosine (riboxin), as well as succinic acid itself. However, some skeptics have not been convinced yet, they oppose the use of these medications in the treatment of critical conditions. The purpose of this article is to expand our views on the natural essence of succinates, their biological role in the human body, highlighting the existing experience of their use in critical conditions, as well as the possibility of their use in the future.