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In August 2022 on a backyard farm in the Moscow region of Russia, mortality was observed among chickens, and all 45 birds of a particular farm died or were slaughtered after the onset of symptoms within a few days. Paramyxovirus was isolated from the diseased birds. Based on the nucleotide sequences of the F and NP gene fragments, it was determined that the virus belonged to subgenotype VII.1 AAvV-1 class II. The cleavage site of the F gene 109SGGRRQKRFIG119 and T in 546 and 555 position of the NP gene were typical for the velogenic type. The genetically closest NDV isolates were found in Iran. The mean time of death of 10-day-old chicken embryos upon infection with the minimal infectious dose was 52 h, which is typical for the velogenic pathotype. The virus caused 100% death of six-week-old chickens during oral infection as well as 100% mortality of all contact chickens, including those located in remote cages, which proves the ability of the virus to spread not only by the fecal–oral route but also by the aerosol route. That demonstrates a high level of pathogenicity and contagiousness of the isolated strain for chicken. However, mice intranasally infected with high doses of the virus did not die.

Introduction. For the treatment of primary inoperable and metastatic solid human tumors with local regional arterial blood flow, a minimally invasive embolization method is used, which causes a decrease in the growth rate and size of the malignancy (cytoreduction), local side effects of which depend on the viscosity of the embolizing agent. Nanostructured ferro- and ferrimagnetics (ferrites) allow selectively achieving not only cytoreduction, but also full effect by following the embolization of magnetic hyperthermia (MHT). Material and methods. The study of a new original embolizing nano-ferrimagnetic nanoembosil with low viscosity was performed with intra-arterial (i.a.) administration to anesthetized animals with intramuscular (i.m.) developed tumors (PC1 and VX2). This allowed us to evaluate its effectiveness using adequate criteria and the method of variation statistics (Fisher-Student’s criterion «t» in the environment of the IBM SPSS 21 package) and statistically significant differences at p≤0.05. Results and discussion. It is shown that nanoembosil in doses of 0.1 and 0.2 ml for rats and 1.5 ml for rabbits is dose-dependent, and in the case of VX2 it is statistically significant (p=0.001) for a long time in 2-6 times inhibits the rate of tumor growth without side effects with long-term stabilization and cytoreduction by 50-65%. Structural analogs of nanoembosil in the practice of medicine there. Conclusion. Thus, nanoembosil can be considered an original effective agent for selective arterial embolization and it is recommended to continue its preclinical study in therapeutic and preoperative modes. Good tolerance of i.a. administration of nanoembosil in the studied doses with no local side effects opens the possibility of studying the possibility of studying it as a thermo-sensitive nanomaterial for low-frequency MHT.

The H7 subtype of avian influenza viruses (AIV) stands out among other AIV. The H7 viruses cir-culate in ducks, poultry, equine and have repeatedly caused outbreaks of disease in humans. In or-der to study the pathogenicity factors of H7N1 viruses, several variants were obtained, starting with laboratory strain, with a history of 12 passages through chicken embryos. This strain, A/chicken/Rostock/R0p/1934(H7N1) (R0p) had only 3 substitution in HA relatively A/Chicken/Rostock/45/34(H7N1), substitution Arg140Gly among them. 10 variants of this strain was obtained and studied to ascertain its biological property, genome stability and factors of patho-genicity. Strain R0p had decreased virulence for chicken, comparing with described in literature virulence of A/FPV Rostock/34 and A/chicken/Rostock/34 viruses. After 10 passages through the chicken lungs variant was obtained much more pathogenic than the starting R0p. The study of in-termediate passages through the chicken lungs showed that the jump in pathogenicity had occurred sharply between the fifth and sixth passage. By cloning these variants, a pair of strains (R5p and R6p) were obtained, and the complete genomes of these strains were sequenced. Single amino acid substitution was revealed, namely reversion Gly140Arg in HA1. This amino acid is located at the head part of the hemagglutinin, adjacent to the receptor-binding site. In addition to the increased pathogenicity for chicken and mice, R6p differs from R5p in the pattern of foci in cell culture and an increased affinity for a negatively charged receptor analogue, while maintaining a pattern of recep-tor binding specificity and the pH optimum of the HA conformational change.

Enzyme L-lysine а-oxidase (LO) exhibits significant antitumor effects by parenteral administration and is promising for clinical trials, particularly in the case of colorectal cancer. The fungi Trichoderma cf.aureoviride Rifai VKM F-4268D is a source of LO. Since there is evidence in the literature of oral use of proteins for therapeutic purposes, it seemed promising to investigate the possibility of such administration route for LO. The goal of the work was to determine the ability of LO to be internalized by the rat small intestine. LO was labeled by Ac-ridinium (LO-Acridinium). Experiments were performed on the rat model using isolated inverted segments of small intestine. The inverted segments were immersed into incubation medium, containing LO-Acridinium. After 30 minutes the samples were taken from the incubation medium and from the intestine segments and relative luminescence was determined by standard flash luminescence method. The amount of absorbed LO-Ac-ridinium was estimated to be 11% for the entire length of the small rat intestine. Based on the optimal total parenteral dose of 400 U/kg for mice the total dose when administered orally was estimated as 4000 U/kg. The absorption of LO through the wall of the rat small intestine was quantitatively characterized, the possibility of its oral administration was proved, and the oral therapeutic dose for mice was estimated.

Anti-integrins are considered as potential anticancer agents capable of inhibiting differentiation and proliferation of various malignant cells, including disseminated melanoma. The possibility of including anti-integrins with different RGD-motives in combined therapy schedules is discussed. We have studied the oridinal recombinant lyophilized protein SAV-RGD (lyo-SAV-RGD), specifically binding to melanoma cells by means of the Tripeptide Arg-Gly-Asp. As models of melanoma of the skin selected amalonaticus MeWo/mel- and pigmented melCher/mel+ with prospectively certain expression of the marker, giving subcutaneous xenograft in mice Balb/c nude. Objective: to evaluate the antitumor activity of lyo-SAV-RGD in vivo on human skin melanoma models melCher and MeWo with different melanogenesis ability and integrin avB3 expression. Both melanomas in vitro were shown to express integrin avB3 detected in melCher/mel+ cells with fluorescent-labeled rat antibodies Luc.H11 according to the expression component integrins avp3, p3-chain (CD61), and MeWo cells/mel- antibodies 23С6. In a high therapeutic total dose of 900 mg/kg, lyo-SAV-RGD inhibited growth of both melanomas in vivo with satisfactory tolerability. Compared to melCher/mel+, MeWo/mel-: T/Cmin=30% (p

The H7 subtype of avian influenza viruses (AIV) stands out among other AIV. H7 viruses circulate in ducks, poultry, equine and have repeatedly caused outbreaks of disease in humans. In order to study the pathogenicity factors of H7N1 viruses, several laboratory variants of the A/FPV/Rostock/34 (H7N1) strain were obtained by passages in the chicken lungs. After 10 such passages, a variant was obtained that differed from the parent virus by amino acid substitutions Val109Phe in PB2, Gln621Lys in PB1, Thr32Ala and Leu586Phe in PA Gly140Arg in HA1 and Ala101Thr in HA2 (numbering by H3), Ser82Arg in M2, Arg118Lys and Met124Arg in NS1. No differences were found in proteins NA, NP, M1 and NS2. The resulting variant was hundreds of times more pathogenic for chickens than the original laboratory variant of the virus. The study of intermediate passages showed that the jump in pathogenicity occurs sharply between the fifth and sixth passage through the chicken lungs. By cloning these variants, a pair of strains (R5p and R6p) were obtained, and the complete genomes of these strains were sequenced. Single amino acid substitution was revealed, namely Gly140Arg in HA1. It is important to emphasize that this substitution is a reversion, since Arg is located in position 140 HA1 of original the A/FPV/Rostock/34 (H7N1) virus (GenBank). This amino acid is located at the head part of the hemagglutinin, adjacent to the receptor-binding site. In addition to the increased pathogenicity, R6p differs from R5p by an increased affinity for a negatively charged receptor analogue, an increased affinity for MDCK cells, while maintaining a receptor specificity profile.

We presented results of monotherapy and combination therapy of transplantable murine tumor models using methionine-gamma-lyase (MGL) and pyridoxine hydrochloride. We studied MGL from Clostridium sporogenes and Citrobacter freundii. We used Lewis lung carcinoma (LLC), melanoma B16, leukemias P388 and L1210 and Fisher lymphadenosis L5178y. Neither monotherapy with MGL nor combination of MGL and pyridoxine demonstrated antitumor activity against P388 and L5178y. In the murine L1210 leukemia model, MGL C. sporogenes injected intraperitoneally in the dose of 2000 U/kg, 11 times with a 12-hour interval increased the life span of mice (ILS=22 %, р=0.035). In the LLC model, the combination of MGL C. sporogenes at a dose of 400 U/kg, i.p., 4 times with a 48-hour interval and pyridoxine at a dose of 250 mg/kg led to tumor growth inhibition (TGI=55 %, р

The effectiveness of L-lysine-alpha oxidase Trichoderma cf. Aureoviride Rifai BKMF-4268D (LO) on models of subcutaneous xenografts of human tumors in athymic mice as well as the effectiveness of combination therapy with known antitumor drugs: cisplatin, irinotecan, etoposide on models of P388 lymphocytic leukemia, Lewis lung (LLC) and B16 melanoma was evaluated. The intraperitoneal injection of LO in a discrete regime at doses of 150-75-75-75-75 E/kg demonstrated inhibition of growth of all studied xenografts of human tumors in athymic mice. The combination of irinotecan+LO on the LLC model gave a significant summative therapeutic benefit with an increase in mouse life expectancy up to 35%. Cisplatin and LO realized a significant (p

This review presents the characteristics of the cellular metabolism of methionine, as well as known data on the mechanisms of the development of methionine dependence in malignant cells. The possibilities of using a non-methionine diet for the control of the tumor growth in patients with various forms of cancer are considered. The newest information about methionine-γ-lyase, an enzyme providing elimination of methionine from plasma, is grouped and summarised. Its role as a potential antitumor enzyme is disclosed. Data on methionine-γ-lyase producers, activity of this enzyme, obtained from various sources, and information on tumor models and cell cultures, showing methionine dependence are summarised.

The review analyzes up-to-date information about specific characteristics of anti-estrogen therapeutic agents with different mechanisms of action with regard to present knowledge of endocrine therapy for estrogen-positive breast cancer (ER+ BC). The paper presents some agents for anti-estrogen therapy of breast cancer - aromatase inhibitors and selective modifiers of biological reactions (SMBR) and their mechanisms of anti-proliferative action. The authors describe significant therapeutic and side effects as well as different options for anti-estrogen combinations. Special emphasis is made on national herbal estrogens/anti-estrogens that have no toxicity associated with the well-known SMBRs. The review presents the structure and characteristics of a perspective phyto-anti-estrogen sekoizolaricirezinol (SEKO), which demonstrated significant anti-proliferative activity with no pro-estrogen action in the in vivo models of ER+ BC.

In the work there are described the parameters of a canceromatosis by the intraperitoneal implantation of the solid tumors: Lewis lung carcinoma (LLC) to syngeneic regular males of C57Bl6j mice and human subcutaneous breast cancer (BC) xenografts BC-1 to immunodeficient females of mice Balb/c nude. There was shown aggressive LLC canceromatosis which was realized as the solid tumor nodule (from 30-40 singles to the total) growths on a peritoneum (parietal or visceral) and a mesenteries or of the intestinal lymphoid nodules, development of space-occupying ascites (to 3.0 ml), and death of mice for 12-14 days. This model is characterized as moderately sensitive to paclitaxel (inhibition of tumor growth by 84% and increasing of life span of mice up to 46%). BC-1 canceromatosis was low aggressive with development of the single (solitary) solid tumor nodule on a peritoneum in the place of implantation and reaching within 3 weeks of average volume to 300 mm3 without accumulation of ascites, decreasing of the life span or death of mice. This model is characterized as moderately sensitive to paclitaxel with inhibition of the tumor growth by 85%. The obtained data give the ground to consider that both intraperitoneal solid tumors represent themselves to be sensitive to systemic chemotherapy for the model of canceromatosis differing in various aggressiveness of a course and specific symptomatics of the process. For an aggressive LLC canceromatosis the evidential base of efficiency has to be formed on the basis of inhibition of growth of the peritoneal tumor nodules in peritoneal cavity and accumulation ofperitoneal ascites, and also the increase of the mice life span, for a nonaggressive BC-1 canceromatosis - inhibition of the growth of the peritoneal tumor nodule.