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

In recent decades, bioengineering and regenerative medicine have shown significant progress in restoring lost teeth and tissue. The review is devoted to modern possibilities of bioengineering intervention in tooth regeneration, including advances in the field of stem cells, 3D printing, biomaterials, gene therapy, and tissue engineering. Embryonic mechanisms of tooth formation and key signaling pathways, such as BMP (Bone Morphogenetic Proteins), FGF (Fibroblast Growth Factors), Wnt, and Shh (Sonic Hedgehog), are the basis for the development of new therapeutic strategies. One of the main directions is the use of different types of stem cells, including dental pulp cells (DPSCs), deciduous teeth (SHED), and periodontal cells (PDLSCs), as well as alternative sources, such as mesenchymal stem cells from bone marrow and adipose tissue. An important aspect is the use of innovative materials, such as biodegradable polymers, natural matrices, and nanostructured coatings, to create 3D scaffolds that support tissue growth. Particular attention is paid to molecular methods of intervention, including the use of growth factors (BMP-2, FGF-2, VEGF, TGF-β), gene therapy (e.g., using CRISPR/Cas9), and controlled gene expression, to activate odontogenesis. Prospects for creating teeth are being considered de novo and with dental organoids as are problems associated with the integration of regenerated tissues into the body, including issues of vascularization, innervation, and immunocompatibility. Important issues remain control over directed cell differentiation, the durability of regenerated teeth, and the ethical and legal aspects of using genetic engineering. Translation of these methods into clinical practice requires the integration of bioengineering, bioinformatics, materials science, and clinical dentistry as well as the development of clinical trials and appropriate legal regulation. In the coming decades, dental regeneration may become an important element of personalized medicine, which will require further improvement of technologies, testing of new biomaterials and more precise control of cellular processes, which will ultimately ensure the successful implementation of this approach in clinical practice.

Myogenic bioengineering has emerged as a promising field aimed at repairing or regenerating damaged muscle tissues triggered by trauma, diseases, or congenital defects. Poly(lactic acid) (PLA) nanofibrous scaffolding has appealed to progressive attraction as an innovative support for prospective therapy in renewal/or repair medicine. Herein, high aspect ratio PLA nanofibers were fabricated using electrospinning and characterized by means of various sophisticated techniques such as XRD, SEM, TGA and FTIR spectroscopy. There is no information regarding the interaction of muscle cells with PLA. Thus, muscle precursor cells were exposed to various doses of electrospun PLA nanoscaffolds to test proliferation and in vitro biocompatibility. Cell viability was assessed by CCK-8 at standard time periods. The structure of treated myoblasts was scanned by a phase contrast microscope and to check the growing profile Bio-SEM was used. Furthermore, antimicrobial activity was explored against Gram-positive Staphylococcus aureus. The findings specify that PLA nanoscaffolds exhibit mild antimicrobial efficiency. Besides, the myoblasts demonstrated proliferative behavior on nanoscaffolds. Our investigation highlights that PLA nanofibers hold significant promise for developing biomimetic cellular scaffolds. Moreover, the PLA nanoscaffolds developed in this study show great potential for tissue engineering, particularly in muscle regeneration. Its high biocompatibility and ability to support myoblast attachment, proliferation and differentiation make it a promising biomaterial implant for regenerative medicine.

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.