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

By comparing the reaction catalyzed by phosphoenolpyruvate carboxylase with the one by the ligase or synthetase, it was suggested here that phosphoenolpyruvate carboxylase (EC 4.1.1.31, PEPC) should be classified as the synthetase. And accordingly it was thought here that the existing classification standard of synthetases put forward by the International Enzyme Committee should be supplemented. That is, synthetases should also include the enzyme which catalyzes the non phosphoric acid portion of a high-energy phosphoric acid compound (except (d)NTP) to synthesize one new substance with the other substance, meanwhile the high-energy phosphoric acid compound above is hydrolyzed in the reaction accompanying with the release of energy stored in its high-energy phosphate bond. It was suggested here that the formula of the reaction catalyzed by the enzyme should be X~Pi + Y + H₂O → H₃PO₄ + X-Y.

The most predominant fatty acid in olive oil, oleic acid (OA), lowers LDL (low-density lipoprotein) cholesterol and may raise HDL (high-density lipoprotein cholesterol). As a result, it effectively improves heart function and prevents heart diseases. In the current research, the OA interaction with HSA (human serum albumin) was evaluated by spectroscopic and computational modeling methods to determine the impact of OA on the body. Observations from the absorption spectra proved the complexation of HSA with OA. An enhancement in the fluorescence intensity shows that interactions between HSA and OA have altered the milieu enclosing the fluorophore and altered the structures of HSA. Van der Waals forces and hydrogen bonds were determined to be the main factors producing the HSA-OA complex by molecular docking. The HSA structure’s α-helix was decreased, as per evidence of far-UV CD spectroscopy. The activity of HSA represented OA binding with HSA in a competitive mode. Investigation of the esterase activity of HSA reveals that OA could inhibit its activity. The information obtained from the MD (Molecular dynamics) simulation proved that the binding of the OA causes stability in the HSA structure, and the structure of the HSA becomes more compact by OA binding and reduces the flexibility of the residues. The data obtained in the present work improves our understanding of the activity and mechanism of binding and provides a valuable experimental approach for investigating the OA-HSA compound.

Post-translational modifications (PTMs) are crucial for all biological processes and offer insights into protein functions, including their activity state, subcellular location, solubility, folding, trafficking, and protein−protein interactions. Amino acids modified by PTMs act as molecular switches, influencing protein function and characteristics, and increasing proteome complexity. Krüppel-like transcription factors (KLFs) are a family of transcription factors that regulate essential cellular processes such as proliferation, differentiation, migration, programmed cell death, and various cancer-relevant pathways. In this study we investigated the effect of phosphorylation on the binding affinity and stability of KLF6-SV1 (Krüppel-like factor 6 splice variant 1) interactions with its binding partners, potentially revealing a mechanism for its oncogenic activity. KLF6-SV1 and binding partners interactions were computationally analyzed to evaluate the role of phosphorylation in KLF6-SV1 on their binding affinity and stability. In the present study, it was found that despite a decrease in the binding force between KLF6-SV1 and TWIST1, KLF6-SV1 and MMP9, KLF6-SV1 and SNAI1 upon phosphorylation, the overall energy of each complex decreased, resulting in increased stability. This suggests that phosphorylation plays a significant role in activating KLF6-SV1 and its partner’s oncogenic activities by making the complex stable. This study provides valuable insights into the underlying molecular mechanism of cancer pathogenesis and suggests that KLF6-SV1 phosphorylation is one of the critical events in cancer pathogenesis.

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.