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

Introduction. The North is a territory affected by a combination of extreme environmental factors that are stressful for all human functional systems. Most researchers come to the conclusion of a hypertensive effect of the climatic and geographical conditions of the North on the human organism. Arterial hypertension is the most common cause of a decrease in the quality of life, disability at a young age, and mortality in northern residents. Therefore, the studies aimed at investigating the epidemiology of the genes that increase the risk of developing arterial hypertension in the territory of the circumpolar zone are especially relevant. Aim. The aim of our study was to study the regional peculiarities of the prevalence of polymorphisms in the genes AGT (rs4762), AGTR1 (rs5186), ADD1 (rs4961), and NOS3 (rs2070744) involved in the regulation of arterial pressure in northern residents of Magadan oblast. Materials and Methods. A cross-sectional, simultaneous study was carried out in the sample of 101 unrelated, almost healthy northern men of Magadan oblast (mainly Europeans) living or born in this territory. The mean age of the subjects was 46.12 ± 1.5 years. Genotyping of polymorphic candidate genes for arterial hypertension was performed using a polymerase chain reaction method. The frequencies of the phenotypes, genes, observed and expected heterozygosity, and genetic distances between different populations were calculated; the matrices of genetic distances were used for a cluster analysis. Results. It was established that the frequencies of the alleles that increase the risk of arterial hypertension were 0.1337 (AGT*T), 0.3564 (NOS3*C), 0.2550 (AGTR1*C), and 0.1832 (ADD1*T). Conclusions. A trend of low frequencies of the candidate genes for arterial hypertension is a regional peculiarity of the genetic profile of the population of northern residents of Magadan oblast. Therefore, when compiling prognostic health cards taking into account an ethno-territorial specificity in the territory of Magadan oblast, it is necessary to take into account not only the genetic risk factors for arterial hypertension, but also the timely lifestyle correction, prescription of preventive measures to prevent the development of arterial hypertension in young age.

A new human uveal melanoma (UM) cell line uMel1 was established by mechanical disintegration of a tumor fragment. uMel1 cells had a stellate dendrite-like shape, contained a lot of brown melanin pigment, and had a low mitotic index. Optimization of cultivation conditions led to an increase in the rate of cell proliferation and was accompanied by the loss of brown pigment. Since the melanin precursor is L-dihydroxyphenylalanine (L-DOPA), the authors analyzed the cultivation of uMel1 cells in the presence of L-DOPA. When L-DOPA was used at a concentration of 20 μg/mL, causing a decrease in cell viability by no more than 10%, melanocytes uMel1 synthesized melanin. It can be concluded that cultivation in the presence of L-DOPA provides the phenotype of melanin-containing melanocytes of uMel1 personal culture under conditions of long-term cultivation. Analysis of cell adhesion molecules N-cadherin (N-cad), E-cadherin (E-cad), and Mel-CAM, as well as receptors of the epidermal growth factor (ErbB) family by flow cytometry, showed that uMel1 cells have a phenotype of N-cad^–/E-cad^–/Mel-CAM⁺/HER2^low/HER3^low, and can be used for the study of targeted drugs to Mel-CAM, HER2 and HER3.

The use of high-performance liquid chromatography in combination with tandem mass spectrometry (HPLC-MS/MS) provides a selective determination of free choline in blood plasma. The instability of the measurement results is due to the residual activity of phospholipases that promote the hydrolysis of phosphatidylcholine ex vivo. The use of EDTA as an anticoagulant and compliance with the cold regime (≤4°C) from blood sampling to the supply of deproteinized and diluted plasma for analysis ensures the accuracy of the analysis (standard deviation not higher than 15%) within the linear range (0.5–10) μg/mL or (5–96) µM. Using a validated method of choline determination in plasma, it was found that the concentration of choline in plasma was (10.0 ± 2.2) μM in a group of people 20–40 years old with no identified diseases (n = 30), while the plasma choline concentration within 90 min rose from the baseline value (8.9 ± 1.3) to the mean value (19.1 ± 4.3) μM and remained at this level during the entire observation period of 72 h in volunteers of the same age and also without identified diseases (n = 50) after a single administration of M-cholinoblocker biperiden at a dose of 2 mg. It has also been confirmed that acute renal failure and advanced age are associated with increased plasma free choline concentrations.

The purpose of the work was to study the influence of natural polysaccharides—arabinogalactan, galactomannan, and carrageenan—on the growth of Klebsiella pneumoniae strains. It was found that carrageenan, especially in high concentrations, most effectively stimulated the growth of these microorganisms. A dependence of the effect of galactomannan on the concentration used was discovered: an inhibitory effect was detected in high doses and a stimulating effect in low doses. Arabinogalactan inhibited the growth of Klebsiella pneumoniae, which could be due to phenolic impurities (bioflavonoids), the presence of which is typical of this polysaccharide. Moreover, this polysaccharide at a concentration of 0.1 mg/mL completely blocked the growth of the studied microbial strains, which can be explained by the antibacterial effect of flavonoids.

Nanomedicine showed the unique benefits in clinical outcomes in comparison with traditional and conventional drugs in the treatment of cancer. In the future, nanomedicine therapy seems to pave the way for new treatments in cancer. In this regard, silica nanoparticles are used in various fields of technology, biomedicine and biosensing techniques due to their unique properties such as stability, biocompatibility, high surface area, significant reactivity and functionalizability. Although there are various physical and chemical methods for synthesizing silica nanoparticles, its synthesis by green method has other significant features such as being environmentally friendly, cost-effective, saving time and eliminating toxic compounds and harmful by-products that increase their application in the field of biomedicine. In the method of green synthesis of silica nanoparticles, various sources such as plants, fungi, bacteria, yeast, actinomycetes, etc. are used. In this narraitive review, various biomedical applications of green synthesized silica nanoparticles are discussed along with their examples.

Background: Calcin is a group of globular peptides with 33−35 AAs that penetrate the cell membrane and specially target RyRs from scorpion venoms, however, which fragment in primary sequence for its transmembrane effect is unclear yet. Methods: eight different fragments of the typical Opicalcin1 (OpiCa1) were synthesized according to the distribution of charged amino acids in primary sequence, followed by the determination of both cell penetration activity and cytotoxic. Results: In all eight OpiCa1 fragments, OpiCa1₁₇₋₃₃, OpiCa1₁₋₁₁, and OpiCa1₂₃₋₃₃ were predicted to be CPPs by CellPPD, and their predicted scores were much smaller than that of TAT, which is consistent with the proportion of basic amino acids. Further fluorescent microscopic experiments found that three fragments FITC labeled OpiCa1₁₇₋₃₃, OpiCa1₁₂₋₂₂ and OpiCa1₂₃₋₃₃ displayed similar cell penetrating capacities to that of TAT. In contrast, flow cytometry found that FITC-OpiCa1₁₇₋₃₃ and FITC-OpiCa1₂₃₋₃₃ have even larger intracellular fluorescent intensities than that of TAT, indicating stronger cell penetrating capacity. Other OpiCa1 fragments displayed slightly cell penetrating effect, of which the fluorescent intensities were slightly larger than that of control but significantly lower than that of TAT, FITC-OpiCa1₁₇₋₃₃ and FITC-OpiCa1₂₃₋₃₃. Moreover, although it is not ruled out the impact on cell viability, overall, all OpiCa1 fragments exhibited no or lower cytotoxicity. Conclusion: The latter half of calcin e.g. OpiCa1 in primary sequence is the main responsible fragment for its membrane penetrating ability, and is also a potential new CPP for further utilization e.g. drug delivery.

Protein tyrosine phosphatase 1B (PTP1B) is implicated as a key negative regulator of the insulin. Plant derived PTP1B inhibitors have emerged as attractive and potent therapeutic agents for the treatment of Type 2 diabetes mellitus (T2DM) and obesity. Rauvolfia serpentina is widely used in Indian Ayurvedic Medical System for the treatment of diabetes. We investigated whether the indole alkaloids of R. serpentina suppress the activity of PTPIB. The structures of 25 indole alkaloids of R. serpentina were obtained from NCBI pubchem and KNApSAcK PRIMe database. The crystal structure of protein PTPIB was retrieved from PDB. The interaction between indole alkaloids and PTP 1B was analyzed using reverse pharmacophore mapping by pharmMapper server. STRING database was applied to find out the association of drug target with other protein. The oral bioavailablity and toxicity profiles were verified by Osiris property explorer, Lazar and admetSAR tools. The prominent metabolic site of indole alkaloides and PTP 1B inhibitor, were predicted using metaprint 2D and autodock tool respectively. Yohimbine exhibited potential binding affinity (ΔG = –5.03 Kcal/mol) against PTP1B. Notably, TYR 46 amino acid residue of PTP 1 B exhibit two π–π stacking interactions with the yohimbine alkaloid in between protein-ligand complex. We proved that the yohimbine is the new lead for design and synthesis of PTP1B inhibitor for the treatment of T2DM.

Background: Pulmonary embolism (PE) is an emergent pulmonary vascular pathology with high morbidity and mortality. This study investigated the relationship between serum lipocalin-2 and -10 levels and clinical score for early mortality risk in patients diagnosed with PE in the emergency department. Methods: The study included 100 patients with PE and 25 healthy controls. The patients with PE were classified as high-risk (Group 1; n = 25), high-intermediate-risk (Group 2; n = 25), low-intermediate-risk (Group 3; n = 25), and low-risk patients (Group 4; n = 25). Serum lipocalin 2 and 10 levels at admission were measured by enzyme-linked immunosorbent assay and compared between the five groups. Results: Serum lipocalin-2 concentration was significantly higher in Group 1 when compared with the other groups (p = 0.003, =0.001, <0.001, and <0.001, respectively). Serum lipocalin-10 level was also higher in Group 1 than in the other groups (p < 0.001 for all). In addition, lipocalin-10 level was higher in Group 2 than in Group 3, Group 4, and the control group (p = 0.05, <0.001, and <0.001, respectively). In the receiver operating characteristic (ROC) analysis of the utility of lipocalin-2 and lipocalin-10 in the differentiation of high-risk PE patients, for lipocalin-2, a cut-off value of 677.7 ng/L had 90% sensitivity and 79% specificity, while for lipocalin-10, a cut-off value of 506.4 ng/L had 90% sensitivity and 87% specificity. Conclusion: Clinical risk scoring for early mortality in PE is important for treatment planning. Serum lipocalin-2 and -10 levels may be useful in early diagnosis and treatment planning in PE.

Objectives: This study examined blood brain natriuretic peptide (BNP) concentrations in newly diagnosed primary hyperthyroidism (PHT) patients, compared them to healthy controls, and examined their correlation with age, gender, and biochemical variables triiodothyronine (T3), tetraiodothyronine (T4), and thyroid stimulating hormone (TSH). The study also sought out a BNP limit for primary hyperthyroidism. Design and methods: The present study included 45 PHT patients without thyroid medication, heart failure, acute coronary syndrome, hypertension, renal failure, pregnancy, Cushing’s syndrome, liver disease, and obesity. In addition, 90 subjects served as the control group in the study. Patients’ and controls’ blood sera were used to measure the concentrations of T3, T4, and TSH by ELFA and BNP by ELISA. Results: The group with PHT had significantly higher BNP levels than the control group. BNP exhibited a significant positive correlation with T3 levels and with age in the PHT group, and its level was higher in females. BNP demonstrated a perfect area under the curve (AU C) where the optimal cutoff value was >32.17, with high sensitivity and specificity. Conclusions: PHT influences BNP levels, potentially reflecting disease presence and severity or thyroid-related complications. BNP levels increase with age, with female patients having higher mean levels. A cutoff value can aid clinicians in diagnosing and managing PHT, guiding evaluation and treatment decisions. Further research is needed to substantiate findings and investigate the underlying mechanisms of BNP’s role in thyroid dysfunction.