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

Chronic kidney disease (CKD) is a serious global public health concern, affecting around 13% of the population. Anemia represents a prevalent consequence of CKD. Anemia improves the probability of cardiovascular disease, accelerates the course of kidney failure, and reduces life quality. Patients with CKD can develop anemia for a variety of reasons, which include but are not limited to lack of renal function. These individuals need a thorough assessment to determine and treat causes of anemia besides erythropoietin insufficiency. However, there is evidence of a lack of circulating erythropoietin (EPO). In this study, we evaluated serum EPO levels in 41 severely anemic individuals with HGB below 7 g/dL, including 184 ESRD patients with and without hepatitis C. The ESRD group with severe anemia showed serum EPO levels of 1.3–1.7 pg/mL, whereas the ESRD group with HCV had an EPO level of 1.0–1.2 pg/mL. Consider using recombinant human erythropoietin (rHuEPO) to treat the condition.

KMT2A gene rearrangements are common genetic events in acute leukemia and lymphoma, particularly in younger patients, and are associated with poor outcome. Due to the wide range of partner genes and breakpoint locations, accurate identification of KMT2A rearrangements can be challenging in clinical molecular diagnostics. To achieve a rapid and cost-effective data on KMT2A translocation partner and fusion gene sequence, we follow a structured approach that includes standard GTG-banded karyotyping, fluorescence in situ hybridization (FISH) with 11q23.3 break-apart or translocation probes, DNA-based next-generation sequencing (NGS) for the entire KMT2A gene, and subsequent confirmation of fusion gene expression using real-time PCR with reverse transcription. Here, we illustrate our diagnostic workflow with a case of pediatric T-cell lymphoma harboring a KMT2A gene rearrangement.

The alarming rise of antibiotic resistance triggered the search for antimicrobial alternatives such as plant-based antimicrobial peptides (AMPs) since they possess a wide range of bioactivities. Herein, we evaluated the antimicrobial probability of peptides from enzyme-digested cocosin-1, improved the antimicrobial probability of selected peptides through engineering, and investigated possible peptide-enzyme interactions. Cocosin-1 was individually digested using pepsin, trypsin, and chymotrypsin, generating AMPs which were analyzed for their antimicrobial probabilities. This approach yielded 9 (CAMPR3) and 25 AMPs (Deep-AmPEP30). The top three peptides with the highest antimicrobial probabilities produced per enzyme were subjected to site-specific amino acid (histidine) substitution while maintaining the conserved sequences intact. The physicochemical properties of the top five engineered peptides were assessed to evaluate their potential efficacy. To understand their mechanisms of action, the original and engineered AMPs with the highest antimicrobial probabilities were modeled and docked against methicillin-resistant Staphylococcus aureus (MRSA) MurE ligase, a bacterial enzyme critical for cell wall biosynthesis. Upon histidine substitution, peptide C1DP-C1 (¹²⁹QRSEREEGERHRW¹⁴¹) displayed the highest antimicrobial probability (82.45%) while peptide CIDP-P2 (³³QSPRRSVSSRNECRIERL⁵⁰) showed the most significant antimicrobial probability improvement (31.70%). Docking studies revealed essential binding interactions, including salt bridges and hydrogen bonding, which may be crucial in AMP-based enzyme inhibition. Overall, this study provides a foundational idea that site-specific changes in the amino acid composition may affect and improve the antimicrobial activity of selected peptides for potential antibacterial therapeutics.

A novel series of 4,4'-methylene bis(N-substituted benzylidene-2-fluoro aniline) derivatives (SE₁ to SE₁₀) was synthesized through the condensation reaction of a 4,4'-methylene bis(2-fluoro aniline) with arious substituted aldehydes. The structural characterization of these compounds was carried out using FTIR, ¹H-NMR, and mass spectrometry techniques. The antimicrobial and antifungal potential of the synthesized compounds was evaluated using the serial dilution method. Among them, SE₃ and SE₉ demonstrated notable antibacterial activity when compared to standard reference drugs, while SE₂ and SE₅ showed good antifungal effects. To investigate the interaction of the synthesized molecules with biological targets, molecular docking studies were performed on all ten compounds. Lanosterol 14-alpha demethylase (PDB ID: 5V5Z) and carbonic anhydrase II (PDB ID: 7SEV) were selected as the target proteins for these studies. Compounds SE₁₀, SE₁, SE₂, and SE₅ exhibited strong binding affinities toward lanosterol 14-alpha demethylase, with docking scores of –11.608, –11.53, –11.485 and –11.386 kcal/mol, respectively. Meanwhile, SE₁ and SE₃ showed the highest binding affinity for Carbonic anhydrase II, with a docking score of –9.504 and –9.37 kcal/mol respectively. Additionally, the physicochemical properties of all synthesized compounds were assessed and reported.

Cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) are malignant tumors that can be characterized by low patient survival rates. They have similar anatomical proximity, morphological similarity, and an overlapping immunohistochemical profile. Even with the aid of modern imaging techniques, it is challenging to differentiate PDAC from distal CCA, as no specific biomarkers have been discovered. Bile is a promising material for research due to the possibility of relatively minimally invasive collection of biomaterial as well as direct contact with the tumor. The purpose of this work is to identify the predominant bile acids for each disease, which will help with the differential diagnosis of PDAC and CCA, while using bile from patients with cholelithiasis as a nontumor control. Bile acids were isolated from the bile of patients with three selected pathologies and studied by tandem chromatography−mass spectrometry. In the bile of patients with cholelithiasis, there are found a variety of isomers of deoxycholic acid as well as an increased proportion of glycolithocholic, glycodeoxycholic, and taurodeoxycholic acids. A predominance of taurocholic acid isomers and an increase in the proportion of glycoursodeoxycholic acid in the bile of patients with CCA is observed. Glycocholic acid is the predominant bile acid in patients with PDAC. Based on the obtained data, a set of bile acids was chosen, making it possible to compile a panel of biomarkers for the differentiation of cholelithiasis, PDAC and CCA.

In the modern world, scientists often discuss problems associated with complications of pregnancy and childbirth in women. The study of cases of repeated fetal loss, stillbirth, intrauterine growth retardation, and preeclampsia leads to the discovery of new aspects of this pathology. In the last decade, an increasing number of studies have reported the presence of patients suffering from seronegative and noncriteria variants of antiphospholipid syndrome, who may have unconventional “noncriteria” antiphospholipid antibodies. Large prospective, multicenter, and multinational studies are needed to improve test standardization. When evaluating a patient with clinical manifestations consistent with obstetric antiphospholipid syndrome but negative serologic tests for standard antibodies, the physician should consider the possibility of developing noncriteria antiphospholipid syndrome. This review will highlight current trends in the identification of patients with reproductive failure associated with noncriteria antiphospholipid syndrome. A review of modern Russian and foreign, primarily English-language, literature devoted to noncriteria antiphospholipid syndrome was conducted. When writing, the latest publications in specialized medical journals and manuals were taken into account. In the future, pregnancy with noncriteria antiphospholipid syndrome will be one of the main tasks of obstetric research, and further developments in this area are needed to develop new therapeutic and preventive possibilities.

This article reports the synthesis, characterization, cytotoxic activity, DNA binding study and antioxidant activity of N-(2-(2-(2-azidoethoxy)ethoxy)ethyl)-4,6-di(aziridin-1-yl)-1,3,5-triazin-2-amine. The synthesized compound was found to possess cytotoxic effects against six various cancer cell lines including HeLa, HCT116, T96G, A549, MCF7, and PANC-1 and non-cancer ECV cell line. Additionally, the capacity for DNA binding was assessed. The addition of 1,3,5-triazine leads to alterations in the UV spectra of DNA. Furthermore, the antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity of N‑(2-(2-(2-azidoethoxy)ethoxy)ethyl)-4,6-di(aziridin-1-yl)-1,3,5-triazin-2-amine was tested. The results show that the mentioned compound had higher antioxidant activity than previously reported comparison of N-(2-(2-(2-azidoethoxy)ethoxy)ethyl)-4,6-di(aziridin-1-yl)-1,3,5-triazin-2-amine. Flow cytometry included analysis of the expression level of PD-L1 and TIM-3 in the presence of N-(2-(2-(2-azidoethoxy)ethoxy)ethyl)-4,6-di(aziridin-1-yl)-1,3,5-triazin-2-amine on HCT116 cell line.

Plant-based preparations with antioxidant and antimicrobial influences can be effectively applied for both the prevention and adjuvant therapy of various diseases. The presented study investigates the antioxidant and pro-oxidant properties of ethanol extract from Origanum vulgare (OVEE) collected in Armenia, focusing on its radical scavenging activity, phenolic and flavonoid content, lipid peroxidation inhibition, nitric oxide (NO) modulation, antioxidant enzyme activity, and gene expression in Escherichia coli NM111 cells. The DPPH assay revealed significant radical scavenging activity (IC₅₀ = 19.97 ± 0.51 μg/mL), in case of catechin (IC₅₀ = 13.08 ± 0.04 μg/mL). OVEE exhibited a high total phenolic (555.08 ± 5.60 μg GAE/mg) and flavonoid contents (31.39 ± 1.16 μg QE/mg), correlating with its antioxidant activity. Lipid peroxidation, assessed via TBARS assay, was significantly inhibited by OVEE (20.72 ± 2.47%) (in case of the positive control -(α-tocopherol) 91.1 ± 1.9%). Unexpectedly, OVEE increased NO levels in E. coli cells, suggesting potential pro-oxidant activity influenced by phenolic compound structure, pH, and metal ion interactions. Enzymatic antioxidant defense was enhanced, with SOD and catalase activities increasing by approximately 40 and 35%, respectively, under the OVEE treatment. Additionally, OVEE induced the expression of the katG::lacZ gene fusion by 1.41-fold, p < 0.001, with further induction observed under oxidative stress. These findings highlight dual antioxidant-prooxidant nature of OVEE, emphasizing its potential antibacterial mechanisms and broader biological significance for therapeutic applications.

Nutriome is a set of alimentary factors for maintaining the body’s adaptive potential. Of particular importance for adaptation processes is the Nrf2/Keap1/ARE signaling system, the key regulatory factor of which is the transcription factor Nrf2. The enzymes that are markers of Nrf2 activation include NAD(P)H-quinone oxidoreductase and microsomal heme oxygenase-1. The aim of the study was to study the effect of minor dietary BAS of polyphenolic nature and indole-3-carbinol on the activity and expression of genes and proteins of Nrf2-regulated enzymes in the liver of rats when they were administered separately and in combination on the body of healthy intact animals. The effects of separate and combined intake of BAS into the body were studied in intact animals, including the following compounds separately and in combination in the diet of male Wistar rats for 14 days: rutin and hesperidin at a dose of 400 mg/kg body weight (b.w.); quercetin and resveratrol at 100 mg/kg b.w.; curcumin and quercetin at 200 mg/kg b.w.; indole-3-carbinol and epigallocatechin gallate at a dose of 50 mg/kg b.w. and 200 mg/kg b.w., respectively. The obtained data indicate that indole-3-carbinol and polyphenols of various classes have a significant effect on the activity and expression of proteins and genes of antioxidant defense enzymes: heme oxygenase-1 and NAD(P)H-quinone oxidoreductase, through the Nrf2/Keap1/ARE signaling mechanism, and at the posttranscriptional level, stimulating the adaptive potential of the body. The combined action of BAS in food can significantly modulate their individual effects.

The results of experimental and clinical studies indicate the involvement of platelets in the process of progression of malignant tumors of different localizations. Studying the effect of corticosteroids on thrombopoiesis in patients with adrenal cortex tumors will allow us to expand our understanding of the pathogenesis of adrenocortical cancer. Twenty two patients with adrenal cortex neoplasms were examined: 11 individuals with adrenocortical cancer (ACC) and 11 ones with adrenocortical adenoma (ACA). The diagnosis was confirmed based on the results of histological examination using the scale of L.M. Weiss. The age of patients was 58 (49–63) years, 5 (23%) of men were included in the study. No differences in the age, gender, or body mass index value between examined individuals with ACC and ACA were detected. In the preoperative period, all patients underwent clinical blood test with determination of leukocyte formula, calculation of systemic immune inflammation index (SII), urine steroid profiles were studied using gas chromatography/mass spectrometry. A larger number of platelets were obtained in ACC patients as compared with examined individuals with ACA: 282 (256‒310) × 10⁹ and 222 (194‒251) × 10⁹, р = 0.004. A lower SII value was detected in ACA patients as compared with ACC patients: 251 (186–354) and 618 (500–703), р = 0.002. Using gas chromatography/mass spectrometry method, higher urinary excretion of glucocorticoid metabolite tetrahydro-11-deoxycortisol, as well as androgens—dehydroepiandrosterone (DHEA) and etiocholanolone (Et) and 11β-OH-androsterone (androstenedione metabolites), progestogens—17-OH-pregnanolone, pregnanediol, pregnanetriol, pregnenediol, was demonstrated in ACC patients as compared with indices in ACA patients (p < 0.007). A linear dependence of the number of blood platelets on urinary excretion of Et (r = 0.81, p < 0.001) and DHEA (r = 0.94, p < 0.001), as well as SII on urinary excretion of DHEA (r = 0.90, p < 0.001), was demonstrated in all examined individuals.