[Prospects for using low-dose radiation in the complex therapy for COVID-19].

This review presents the literature data of new approaches for the treatment of COVID-19 with low doses of radiation (LDR). In addition, data on the use of LDR for the treatment of various disorders, in particular pneumonia, a number of inflammatory processes of various etiology, as well as Alzheimer's disease are discussed. The mechanisms of LDR action are briefly described, associated with the activation of the immune system and antiinflammatory response due to the effect on the processes of oxidative stress, which is reflected in an increase in the activity of cytokines (interleukin- (IL-) 6), changes in the expression of a number of genes (such as P53 and NF-κB (p65)) and long non-coding RNAs (ncRNAs) (the authors' own data are presented).

Changes in the Activity of Genes Involved in the Regulation of Hematopoiesis during Tumorigenesis in Irradiated Mice.

We used 183 F1 CBA×C57Bl hybrid mice to study the delayed effects of low-power long-term γ-irradiation at a dose of 12.6 Gy (10 mGy/min) 8 and 10 months after the treatment. Eight months after the treatment we found the increased expression of the transcription factor NFκB and its target genes iNOS and G-SCF in the bone marrow (BM).

Investigation of Thionins from Black Cumin (Nigella sativa L.) Seeds Showing Cytotoxic, Regulatory and Antifungal Activity.

Thionins (NsW1 and NsW2), earlier isolated from the seeds of endemic Middle-Asian black cumin (Aligella sativa L.), showing signilicant inhibitory action on some bacterial and yeast pathogens were investigated for cytotoxic properties against several tumor cell lines (AsPC-1, Colo357, RD and Jukart) in vitro within nano- and micromolar ranges of the active concentrations and as modulators of expression of the genes controlling conversion of normal cells to malignant ones. Suppression of the expression of the genes from MMP, RhoA, miR21 families in human rhabdomyosarcoma (RD) cells was observed, whereas the influence of the molecules on the genes in normal blood cells was not identified.

[Comparative analysis of natural and synthetic antimutagens as regulators of gene expression in human cells under exposure to ionizing radiation].

This paper studies the effect of plant peptides of thionine Ns-W2 extracted from seeds of fennel flower (Nigella sativa) and β-purothionine from wheat germs (Triticum kiharae), as well as a synthetic antimutagen (crown-compound), on the expression of several genes involved in the.control of cellular homeostasis, processes of carcinogenesis, and radiation response in human rhabdomyosarcoma cells (RD cells), T-lymphoblastoid cell line Jurkat, and blood cells. All of these agents acted as antimutagens-anticarcinogens, reducing the expression of genes involved in carcinogenesis (genes of families MMP, TIMP, and IAP and G-protein genes) in a tumor cell.

Antimutagenic activity of wheat polypeptides in human cells exposed to cadmium chloride.

Antimutagenic effects of polypeptides isolated from Triticum kiharae wheat plantule extracts have been studied on human cells exposed to cadmium chloride. The most effective polypeptide Tk-AMP-BP β -purothionin exhibited higher antimutagenic activity than wheat water extract and another peptide isolated from the same wheat species, Tk-AMP-γ 2 defensin; it also produced a pronounced antioxidant effect. This polypeptide can be used as a preventive agent for reducing the mutagenic potential of some environmental pollutants and for correction of human diseases associated with the defense system defects.

[Expression of P53, NPM1, Kras, c-Myc, p14(ARF) genes in blood cells of cancer patients before and after radiation therapy].

The mRNA levels of P53gene, as well as NPM1, Kras, c-Myc, p14(ARF) genes, which, according to the published data, code for the proteins regulating the p53 activity, were studied using RT-PCR method in blood cells of patients with different localization of tumor process (prostate cancer, breast cancer and head and neck cancer) before and after application of radiation therapy. Changes in gene expression of cancer patients were compared with the control group of healthy donors. We have established that all patients had a decreased level of the Kras gene expression even before radiotherapy; moreover, the group of patients with prostate cancer had a low content of mRNA in NPM1 and p14(ARF), and the group of patients with head and neck cancerhad a reliably reduced mRNA in P53, NPM1 and p14(ARF).

[Antimutagenic activity of wheat beta-purothionin Tk-AMP-BP].

Antimutagenic activity on human RD cells was studied for beta-purothionin Tk-AMP-BP isolated from seeds of wheat Triticum kiharae, which has a higher stress resistance. Cadmium chloride at 5 x 10(-6) M was used as a mutagen. The numbers of DNA breaks in mutagen-treated and intact cells were inferred from the single-stranded to double-stranded DNA ratio and expressed as protection coefficients.

[The peculiarities of polymorphism of XPD and XRCC1 repair genes in cells of Down and Ehlers-Danlo syndrome patients characterized by increased radiosensitivity].

Codon 312 and 751 polymorphisms ofXPD gene and codon 399 polymorphism of XRCC1 gene of peripheral blood lymphocytes in patients with Down syndrome (DS) (46 individuals), Ehlers-Danlo syndrome (EDS) (47 individuals) and in a group of healthy donors (control) (40 individuals) have been studied. Frequency of XPD genotype (G312G) coding for the most effectively functioning form of XPD protein was lower in patients with DS (26%) than in a group of healthy donors (42.5%) (p = 0.

[Investigation of detoxification polymorphisms genes, methylenetetrahydrofolate-reductase (MTHFR) and P53 in the radiosensitive human cells].

The genes of detoxication, MTHFR and p53 were studied in Down' and Ehlers-Danlos syndrome cells. The frequency GSTM1(0/0) genotype in Down syndrome patients was in 1.5 times higher than in control cells (p < 0.

[Protection of radiosensitive human cells against the action of heavy metals by antimutagens and adapting factors: association with genetic and protein polymorphisms].

Cells of a diploid line obtained from embryos with the Down's syndrome, known to be unable to repair gamma-induced DNA damage, were treated with natural (garlic extract, retinol) and synthetic (crown compound) antimutagens and with adapting factors (heat shock, low CdCl2 concentrations, 10(-8) M). The protective effect was evaluated by registering DNA breaks and cell survival, and the protection coefficients were calculated. The most effective results were obtained with the use of the garlic extract and retinol.

[Gene polymorphisms in patients with Down's syndrome].

Polymorphisms of glutation-S-transferase (GSTM1, GSTT1 GSTP1) and methylentetrahydrofolate reductase (MTHFR) genes have been studied in DNA from blood lymphocytes of 18 patients with Down's syndrome and 61 controls. Frequencies of normal alleles of GST genotypes were lower in patients as compared to the controls. A DNA analysis of 11 patients and 17 controls revealed the presence of mutations in region 246-250 of exon 7 of the p53 gene in 4 patients.

[Adaptive response--the general biological tendency: facts, hipothesis, questions].

It is leading up to the proofs testifying about the general-biological nature of adaptive response (AR), which is similar unspecific defense effect: for example, small doses induce cytokines synthesis, providing the resistance to different infectious agents. The connection between AR, DNA-repair, anti-oxidative status, expression of TP53 gene is discussed. The absence of AR at some patients can be explained either individual sensitivity to challenging treatment or criteria of the estimation (chromosome aberration, apoptosis et.

Polymorphism of detoxification genes and cell resistance to mutagens in patients with Ehlers-Danlos syndrome.

Study of polymorphism in 3 genes of the glutathione S-transferase family (GSTM1, GSTT1, and GSTP1) in children with Ehlers-Danlos syndrome whose cells were defective in repair of gamma-induced DNA damages revealed accumulation of GSTM1(+) genotypes compared to children of the control group. Generation of reactive oxygen species by neutrophils from patients with this syndrome was higher than in healthy donors. Our results indicate that glutathione S-transferase genes are involved in the resistance to mutagenic agents and demonstrate medical and genetic peculiarities of patients with Ehlers-Danlos syndrome.

[Antimutagenes' protection action in human repair-defected cells].

The action of natural (garlick extract, retinol) and of synthetic (crown-compound) antimutagenes in lymphotytes with gamma-radiation-induced inhibition of DNA-damages repair in cases of Elers-Danlos, syndrom, progeria and gomocystinurea was studied. Antimutagen cells defence from mutagenes was shown at all cases except one: progeria cells treated by retinol. Thus the repair-deficient cells resistance against mutagenes could be increased by antimutagenes.

Antimutagenic characteristics of new diazacrown compounds with N-carboxyalkyl substitutes.

Two new benzodiaza-15-crown-5 compounds containing two N-hydroxycarbonylmethyl or N-hydroxycarbonylpropyl substitutes were synthesized. The first of these compounds exhibited more pronounced protective effects towards human cells according to criteria of primary DNA injury and cell survival after exposure to gamma-radiation and CdCl2; by antimutagenic activity this compound was comparable to garlic extract. The antimutagenic effect of these compounds was realized not through the antioxidant mechanism.

[Genetic polymorphism of glutathione-S-transferases and inhibition of DNA repair].

A complex investigation of different cell defence systems, such as: DNA repair, antioxidant system (SOD), xenobiotic detoxification system (glutathione-S-transferases M1 and T1), radioadaptive response (RAR) in lymphocytes of patients with hereditary disease of connective tissue (Elers-Danlose syndrome) was carried out. The frequency of genotype GSTM1 (0/0) in children with Elers-Danlose syndrome (23%) is lower as compared to the control group (44%). The lymphocytes of children with Elers-Danlose syndrome were characterized by reduced ability to repair gamma-induced damage of DNA.

[Unsolved problems of human cell defence against radiation].

The complex of human cell defence systems against gamma-radiation was investigated: DNA repair, antiradical system, GST-family M1 and T1, radioadaptive response. Were compared in repair-deficient cells the action of natural (carlic extract) and synthetic (crown-compound) antimutagens. New approach related to the detection of the activity of different defence systems is developing.

[Mechanisms of human cell protection associated with genetic polymorphism].

Systems ensuring protection of human cells against endogenous and exogenous mutagenic factors are considered in terms of genetic polymorphism. Some protection mechanisms are described, including those connected with capturing free radicals, biotransformation of xenobiotics, excision repair of DNA damage (excision of nitrous bases, nucleotides, mismatch repair). A special section is devoted to some issues of using antimutagens in context of genetic polymorphism.

[DNA repair and antioxidant defence in the repair-deficient human cells (Marfan's syndrome) after gamma-irradiation].

DNA repair synthesis (RS) was investigated in lymphocytes of healty donors and repair-deficient cells (Marfan's syndrome), treated with inhibitor of superoxidedismutase (SOD)--TRIEN--after gamma-irradiation. Significant difference was revealed in cells of healthy donors and Marfan's syndrome: in cells of healthy donors TRIEN stimulated DNA RS whereas this effect didn't observed in Marfan's syndrome cells. So it is possible to suppose that SOD activity is different in normal and gamma-repair-deficient cells.

[Differentiation of activity of a superoxide dismutase inhibitor in human cells exposed to radiation, chemical mutagens and radioadaptive response].

The superoxide dismutase (SOD) inhibitor, TRIEN, which enhanced the formation of gamma-induced DNA breaks in cells of healthy donors and patients with Marfan syndrome and Bloom syndrome (repair-defective hereditary diseases), had virtually no effect on the formation of radioadaptive response (RAR) in these systems. Similar results were obtained in studies on cell survival: TRIEN facilitated mortality in cells irradiated with gamma-rays but did not affect RAR formation. TRIEN also increased the deleterious effect of CdCl2, which indicates that SOD apparently plays a certain role in cell defence against this mutagen.