Biochemistry, Genetics and Molecular Biology, Cell Biology, Cancer Research
8
Scopus Publications
Scopus Publications
TREC and KREC concentration in the screening of inborn errors of immunity Gulnara G. Suleymanova, Vladislav A. Vasilichin, Nailya Kh. Setdikova, Evgeniy A. Frolov, Tatiana N. Myasnikova, et al. Russian Journal of Allergy, 2026 BACKGROUND: The lack of accessible screening for inborn errors of immunity in adults significantly complicates the diagnosis of these conditions. In more than half of the cases, this leads to delayed disease detection and the development of irreversible complications in patients.AIM: To determine reference intervals for TREC and KREC concentrations in adults and evaluate the possibility of their use for inborn errors of immunity screening using the “NeoScreen SMA/TREC/KREC” test system.METHODS: A single-center observational cross-sectional controlled non-randomized study was conducted involving 101 patients. The study included groups with humoral and combined immune defects, divided into subgroups with predominant humoral immune defects (antibody synthesis disorders) and combined immune defects, as well as a control group of conditionally healthy participants. TREC and KREC levels were determined using polymerase chain reaction. The study was conducted from September 2024 to August 2025. Statistical analysis included group comparisons (Mann–Whitney and Kruskal–Wallis tests), ROC analysis. Reference intervals were determined using the direct method according to International Federation of Clinical Chemistry and Laboratory Medicine recommendations. Statistical significance was confirmed at p 0,05.RESULTS: The study included 101 participants: 46 patients in the control group and 55 patients with inborn errors of immunity. Statistically significant differences in TREC and KREC levels were observed between healthy participants under 39 years and over 40 years (p 0,001 and p = 0,003, respectively). Subgroup analysis showed: in the humoral immune defects subgroup, KREC levels demonstrated area under curve — 0,87, specificity — 95 %, sensitivity — 68 %. In the subgroup with combined immune defects, the method did not show statistically significant differences with the control group when comparing TREC and KREC levels (p = 0,639 and p = 0,092, respectively).CONCLUSION: The development of separate threshold values for patients over 40 years of age is required. The method is effective for screening humoral immune disorders but is not suitable for combined forms of inborn errors of immunity. Despite the high specificity and sensitivity of KREC as a diagnostic marker, the method cannot be recommended as a replacement for existing diagnostic methods due to the availability of more accessible and effective screening approaches.
A Novel Pot-Economy Approach to the Synthesis of Triantennary GalNAc-Oligonucleotide Artem Evgenievich Gusev, Vladimir Nikolaevich Ivanov, Nikolai Andreevich Dmitriev, Aleksandr Viktorovich Kholstov, Vladislav Aleksandrovich Vasilichin, et al. Molecules, 2024 N-Acetylgalactosamine (GalNAc) is an efficient and multifunctional delivery tool in the development and synthesis of chemically modified oligonucleotide therapeutics (conjugates). Such therapeutics demonstrate improved potency in vivo due to the selective and efficient delivery to hepatocytes in the liver via receptor-mediated endocytosis, which is what drives the high interest in this molecule. The ways to synthesize such structures are relatively new and have not been optimized in terms of the yields and stages both in lab and large-scale synthesis. Another significant criterion, especially in large-scale synthesis, is to match ecological norms and perform the synthesis in accordance with the Green Chemistry approach, i.e., to control and minimize the amounts of reagents and resources consumed and the waste generated. Here, we provide a robust and resource effective pot-economy method for the synthesis of triantennary GalNAc and GalNAc phosphoramidite/CPG optimized for laboratory scales.
Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells Kirill S. Sadovnikov, Dmitry A. Vasilenko, Yulia A. Gracheva, Nikolay A. Zefirov, Eugene V. Radchenko, et al. Archiv Der Pharmazie, 2022 A series of novel antimitotic agents was designed using the replacement of heterocyclic cores in two tubulin‐targeting lead molecules with the acylated 4‐aminoisoxazole moiety. Target compounds were synthesized via heterocyclization of β‐aryl‐substituted vinylketones by tert‐butyl nitrite in the presence of water as a key step. 4‐Methyl‐N‐[5‐methyl‐3‐(3,4,5‐trimethoxyphenyl)isoxazol‐4‐yl]benzamide (1aa) was found to stimulate partial depolymerization of microtubules of human lung carcinoma A549 cells at a high concentration of 100 µM and to totally inhibit cell growth (IC50 = 0.99 µM) and cell viability (IC50 = 0.271 µM) in the nanomolar to submicromolar concentration range. These data provide evidence of the multitarget profile of the cytotoxic action of compound 1aa. The SAR study demonstrated that the 3,4,5‐trimethoxyphenyl residue is the key structural parameter determining the efficiency both towards tubulin and other molecular targets. The cytotoxicity of 3‐methyl‐N‐[5‐methyl‐3‐(3,4,5‐trimethoxyphenyl)isoxazol‐4‐yl]benzamide (1ab) to the androgen‐sensitive human prostate adenocarcinoma cancer cell line LNCaP (IC50 = 0.301 µM) was approximately one order of magnitude higher than that to the conditionally normal cells lines WI‐26 VA4 (IC50 = 2.26 µM) and human umbilical vein endothelial cells (IC50 = 5.58 µM) and significantly higher than that to primary fibroblasts (IC50 > 75 µM).
Effects of metal oxide nanoparticles on toll-like receptor mRNAs in human monocytes Vladislav A. Vasilichin, Sergey A. Tsymbal, Anna F. Fakhardo, Elizaveta I. Anastasova, Andrey S. Marchenko, et al. Nanomaterials, 2020 For the widespread application of nanotechnology in biomedicine, it is necessary to obtain information about their safety. A critical problem is presented by the host immune responses to nanomaterials. It is assumed that the innate immune system plays a crucial role in the interaction of nanomaterials with the host organism. However, there are only fragmented data on the activation of innate immune system factors, such as toll-like receptors (TLRs), by some nanoparticles (NPs). In this study, we investigated TLRs’ activation by clinically relevant and promising NPs, such as Fe3O4, TiO2, ZnO, CuO, Ag2O, and AlOOH. Cytotoxicity and effects on innate immunity factors were studied in THP-1(Tohoku Hospital Pediatrics-1) cell culture. NPs caused an increase of TLR-4 and -6 expression, which was comparable with the LPS-induced level. This suggests that the studied NPs can stimulate the innate immune system response inside the host. The data obtained should be taken into account in future research and to create safe-by-design biomedical nanomaterials.