Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry最新文献

This review is devoted to some areas of medicinal application of pyrrole-containing macroheterocycles. Two main application areas were discussed: treatment and imaging. The treatment part is divided into anticancer and photodynamic antimicrobial chemotherapy. Novel hybrid and encapsulated photosensitizers were concerned. Successful attempts to inactivate various viruses, including avian influenza H5N8 and SARS-CoV-2, are discussed. Imaging aspects include fluorescence imaging and magnetic resonance imaging. The fluorescence imaging part concerns not only the traditional porphyrin/phthalocyanine ligand fluorescence, but also the near-infrared emission of the central lanthanide ion. The review examines the areas of application of new promising tripyrrole photosensitizers—boron subphthalocyanines. Previously, these compounds attracted the attention of researchers only as materials for organic electronics. However, these compounds are currently considered promising candidates for photodynamic therapy.

The leading cause of vision loss in older adults is age-related macular degeneration (AMD). AMD is a multifactorial neurodegenerative disease of the retina that is becoming the leading cause of central vision loss in people over 55 years of age. The course of AMD depends on many interacting factors: genetic, environmental, and epigenetic, including changes in microRNA expression patterns. MicroRNAs are a large group of small noncoding regulatory RNA molecules that modulate the expression of target genes by blocking translation through complementary binding of messenger RNAs. The freeze–thaw stability of microRNAs in plasma/serum/urine, efficient recovery, and the availability of quantitative detection methods expand the possibilities of their use as biomarkers as well as potential mediators of physiological and pathological processes. Assessing the circulating pool of miRNAs in various biological fluids, such as blood plasma, is considered a promising approach to diagnosing AMD and assessing the effectiveness of future therapy, which may contribute to early detection of the disease and monitoring of AMD progression. The review summarizes recent studies with a focus on clinical and experimental studies of neovascular AMD, which have established the involvement of various microRNAs in the processes of pathological angiogenesis and the possibility of their use as biomarkers and therapeutic targets.

The series of new organotin complexes on the basis of bis(trimethylsilylmethyl)tin diсhloride, 1,1-dichloro-1-stanna-3,3,5,5-tetramethyl-3,5-disila-4-oxacyclohexane, and mono- and bidentate ligands—2,2'-bipyridyl, 1,10-phenanthroline, and 1-methyl-, 1-vinyl-, and 1-allylimidazoles—have been synthesized. The complexes were characterized by elemental analysis; ¹Н-, ¹³С-, and ¹¹⁹Sn-NMR spectrometry; and X-ray data. Cytotoxicity in vitro of the complexes for some lines of human cancer cells was investigated.

The study compared the content of IgG specific to 90 food antigens in practically healthy people and in people with metabolic syndrome. It has been shown that IgG levels to food antigens are higher in metabolic syndrome, which may be due to an increase in the activity of paracellular transport of food antigens and disruption of the intestinal barrier function caused by the influence of proinflammatory cytokines and hyperglycemia. Gender characteristics of IgG content to food antigens were established, with a significant increase in them in women against the background of a higher level of markers of general inflammation both in the group of practically healthy people and in those with metabolic syndrome.

High glucose variability (GV) and increased glycation may play a role in the development of diabetes complications. We aimed to assess associations between serum levels of glycation markers and GV metrics in people with type 1 diabetes (T1D). This study included 128 adult patients with T1D and 30 normoglycemic individuals as control. Time in ranges (TIRs), coefficient of variation (CV), mean amplitude of glycemic excursions (MAGE), and mean absolute glucose changes (MAG) were derived from continuous glucose monitoring. Serum glycated albumin (GA), pentosidine, advanced glycation end-products (AGEs), and soluble receptor for advanced glycation end products (sRAGE) were assessed by ELISA. Serum concentrations of GA, pentosidine, and AGEs were increased in patients when compared to control, sRAGE showed no difference. The levels of pentosidine and AGEs were significantly higher in patients with non-targeted TIR than in those with TIR >70%. The concentrations of AGEs were also higher in those with CV ≥ 36%. In patients with diabetes, all glycation products correlated positively with mean glucose, time above range, and MAGE; pentosidine and AGEs correlated negatively with TIR and positively with MAG. Serum GA and pentosidine demonstrated positive correlations with CV. In multivariate stepwise regression analysis, HbA1c, estimated glomerular filtration rate, and CV were associated with GA, while HbA1c was predictor for AGEs. The results suggest that GV may contribute to increased glycation, at least at the early stages, in people with T1D.

RNA sequencing (RNAseq) is currently a method of choice for the high-throughput RNA-level analysis of gene expression. Furthermore, RNAseq data can be used for the prediction of numerous cancer biomarkers e.g. microsatellite instability, tumor mutational burden, gene signatures, and immunohistochemical markers expression. In this analysis, central step is comparison with the pre-existing pool of normal/healthy control tissue profiles. However, technically different RNAseq platforms and protocols usually provide poorly compatible gene expression outputs that can be difficult to pool together and analyze in a direct comparison due to platform/protocol-specific bias. We recently published Oncobox RNA sample preparation and sequencing protocol for Illumina platform that can be used for the analysis of gene expression in cancer molecular diagnostics to personalize treatments, as validated in preclinical and clinical studies. Here we report adaptation of this protocol for DNBSEQ-G50 engine of a competitor MGI sequencing platform. We demonstrate common clustering and similar gene expression portraits for the RNAseq profiles obtained for the same 16 formalin-fixed, paraffin-embedded model experimental cancer biosamples using both Illumina and MGI sequencing platforms. The adopted Oncobox protocol enables retention of the case-to-normal ratios, calculated values of molecular pathway activation, and also of predicted cancer drug efficiency scores. Our findings suggest clinical applicability of Oncobox molecular diagnostics with both Illumina and MGI sequencing platforms. This also evidence that no specific data harmonization is needed to compare the molecular profiles obtained with either platform when using the Oncobox protocol, e.g. with the previously published ANTE experimental panel of normal tissues.

L-asparaginase, which hydrolyzes asparagine and, to a lesser extent, glutamine, initially used to treat acute lymphoblastic leukemia and other hematological malignancies, may soon become a therapeutic agent for the treatment of a wide group of oncological diseases, as more and more evidence is accumulating that not only leukemia cells and lymphomas but also various solid tumors are sensitive to the action of this enzyme. However, like any other drug, L-asparaginase is not always effective; moreover, its use often leads to unwanted side reactions. Taking this into account, for the successful use of asparaginase, it is advisable to study and introduce into clinical practice prognostic markers that make it possible to predict in advance its effectiveness in the treatment of a particular patient. This review highlights various biochemical factors that influence the sensitivity of tumor cells to L-asparaginase. The asparagine synthetase and glutamine synthetase genes are examined in detail; the influence of their expression levels on the sensitivity of tumors to asparaginase has been studied in numerous experiments. In addition, “nonclassical” factors are considered, such as the expression of glutamine transporter genes, opioid receptors, methylation of the asparagine synthetase gene promoter, the activity of some signaling pathways, and the activity of the PTEN protein. The presented data can contribute to the creation of a more holistic and accurate system of markers that can be used to predict the sensitivity of tumor cells, including solid ones, to L-asparaginase.

The task of studying radiation “bystander effects” at the organism level was set in the work. Irradiated and nonirradiated mice that were kept together were used in the experiment. Mice were irradiated at a dose of 3 Gy in a research radiobiological gamma installation with the sources of ¹³⁷Cs. The number of leukocytes and relative number of lymphocytes in the peripheral blood of mice were estimated 3, 7, 14, 30, 60, and 90 days after the beginning of the experiment. In nonirradiated “bystander” mice kept with irradiated mice both in the cages without a partition and with a partition, there is a possible trend towards a decrease in the number of leukocytes as compared with indices in the biocontrol. During the analysis of relative number of lymphocytes, a trend towards a decrease in the index in “bystander” mice was demonstrated both when keeping without a partition and with a partition. In nonirradiated “bystander” animals when keeping with irradiated animals in the cage with a partition, a statistically significant decrease in the relative number of lymphocytes in the peripheral blood was registered on days 3 (t = 2.13; p = 0.047), 30 (t = 2.94; p = 0.01), and 90 (t = 3.07; p = 0.01) after irradiation as well as when keeping in the same cage with irradiated mice without a partition on day 60 (t = 2.24; p = 0.038) after the beginning of the experiment. A “bystander effect” in nonirradiated animals is one of possible explanations for the detected changes. In irradiated animals that were kept in the same cage with a partition together with nonirradiated animals, a statistically significant increase in the relative number of lymphocytes was registered on days 3 (t = 2.6; p = 0.02), 14 (t = 2.61; p = 0.018), and 60 (t = 2.38; p = 0.03) (“rescue effect”). Based on data obtained in the present experiment, it is assumed that the radiation “bystander effect” can have the opposite nature; that is, nonirradiated organisms are able to reduce the radiation effects in irradiated individuals (“rescue effect”).

Atherosclerosis is a disease of blood vessels which is caused by inherited and acquired factors and leads to different complications in the body including blood clot formation, a serious condition that can threat human life. This study aims to measure the prevalence of thrombophilia gene mutations; Factor V Leiden (FVL, G1691A) and F-II (G20210A) in Jordanian patients with atherosclerosis. Using real-time PCR, the prevalence of heterozygous and homozygous variants of FVL (G1691A) were 11.32 and 1.87% respectively. In F-II (G20210), the prevalence was 1.87 and 0.31% for heterozygous and homozygous variants, respectively. Comparing mutants’ frequencies between patients with atherosclerosis and healthy people (control) showed no significant difference suggesting no relation of these mutants and thrombus formation in atherosclerotic patients, however, among patients’ group there was a significant difference in the prevalence of FVL (G1691A) variants between male and female populations and insignificant difference for F-II (G20210). In conclusion, the results of this study showed no relation of inherited F-V and F-II gene mutations in blood clot formation in atherosclerotic patients, suggestion that blood clot formation is related only to environmental factors belong to the nature of atherosclerotic plaque which trigger platelets and clotting proteins activation.

The authors examined 111 practically healthy individuals (66 women and 45 men aged 46–55 years) living and working in the Spitsbergen archipelago as well as in Murmansk oblast. The comparison group included 118 practically healthy people (59 women and 59 men, 46–55 years old) born and living in Arkhangelsk oblast. The hemogram of peripheral venous blood, the content of lymphocytes with the phenotypes CD3+, CD4+, CD8+, CD10+, CD16+, CD19+, CD23+, CD25+, and CD71+ were studied using indirect immunoperoxidase reaction and flow cytometry; concentrations of brain natriuretic peptide Nt-pro-BNP, endothelin-1, total NO, endogenous NO₂, nitrate NO₃, cortisol, norepinephrine, adrenaline were studied using enzyme-linked immunosorbent assay. It has been established that individuals living in the Arctic and territories equated to the regions of the Far North have a higher concentration of Nt-pro-BNP in the venous peripheral blood. Elevated blood concentrations of Nt-pro-BNP are associated with higher levels of norepinephrine and cortisol against the background of less pronounced concentrations of adrenaline and endothelin-1 as well as redistribution of lymphocytes and monocytes from the circulating pool to the marginal pool.