Introduction: Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal brain injury and long-term neurodevelopmental impairment, and current therapies only partially prevent adverse outcomes. Although recombinanterythropoietin is neuroprotective via EPOR–CD131 (βcR), its use is limited by hematopoietic side effects, motivating evaluation of non-hematopoietic peptide analogs such as Ara-290 and Epobis in HIE. Materials and Methods: Neonatal hypoxia-ischemia was induced in 9-day-old CD-1 mice (n = 204) using a modified Rice–Vannucci model, and animals were stratified into mild and moderate severity groups 3 hours later by laser speckle contrast imaging (RFLSI-ZW) before assignment to treatment. EPO (5000 IU/kg) and Epobis (20 mg/kg) were administered subcutaneously every 24 hours and Ara-290 (30 µg/kg) intraperitoneally every 12 hours for 7 days, after which motor-coordination performance, macroscopic lesion volume, and expression of IL-4, IL-1b, IL-6, and TNF-α were assessed. Results: In both mild and moderate HIE, Epobis provided the most consistent neuroprotection, improving motor performance and neurological outcomes and being the only treatment to significantly reduce macroscopic lesion volume. EPO produced moderate functional benefits, whereas Ara-290 showed a less stable efficacy profile, with limited or absent effects in several behavioral and morphological endpoints. Conclusion: In mild HIE, Epobis showed the strongest neuroprotection, improving motor-coordination performance, reducing neurological deficits, and producing the greatest reduction in macroscopic lesion volume, whereas EPO and Ara-290 had only moderate effects. In moderate HIE, Epobis and EPO most consistently improved motor outcomes, but only Epobis significantly reduced lesion volume and neurological symptom severity and produced the most pronounced immunomodulation.

Neurotrophic factors (NTFs), including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), and vascular endothelial growth factor (VEGF), play a central role in neuronal survival, plasticity, and regeneration. Despite their distinct etiologies and temporal profiles, stroke (both ischemic and hemorrhagic), traumatic brain injury (TBI), and neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD) and Parkinson’s disease (PD), converge on a common pathophysiological phenotype characterized by excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation, blood-brain barrier (BBB) disruption, and neuronal apoptosis. Neurotrophic factors modulate these pathological cascades through tropomyosin receptor kinase (Trk) receptors, p75 neurotrophin receptor (p75NTR), and related signaling pathways, thereby supporting neuroprotection, neurogenesis, and synaptogenesis. Experimental evidence from preclinical models demonstrates robust beneficial effects of neurotrophin-based interventions in stroke, TBI, AD, and PD across protein, gene, and cell-based strategies. However, clinical translation remains severely limited. Early-phase clinical trials of adeno-associated virus (AAV)-mediated GDNF and neurturin gene therapy for PD, ex vivo NGF gene therapy for AD, and BDNF gene therapy for AD have confirmed acceptable safety profiles but yielded modest or inconsistent efficacy, largely due to constraints in brain delivery, the need for invasive neurosurgical procedures, restricted target coverage, suboptimal control of expression, and marked patient heterogeneity. Consequently, the principal barrier to clinical success is not biological validity, but the lack of safe, effective and scalable delivery platforms capable of bypassing or functionally modulating the BBB. In this review we synthesize shared pathophysiological mechanisms linking stroke, TBI and NDDs; examine the biology, receptor systems, and signaling pathways of key neurotrophic factors; summarize preclinical evidence for their therapeutic potential; and critically evaluate current delivery strategies, including viral vectors, lipid nanoparticles, exosomes, cell-based therapies, small-molecule mimetics, and intranasal administration. We conclude that overcoming delivery barriers through development of improved viral and non-viral platforms, minimally invasive administration routes, controllable expression systems, and rational patient stratification based on disease stage and biomarkers will be essential to fully realize the neuroprotective and neuroregenerative potential of neurotrophin-based therapies for acute and chronic brain disorders.

Introduction: Neonatal hypoxia-ischemia (HI) remains one of the most significant causes of perinatal central nervous system injuries and subsequent neurodevelopmental disorders. The development of new therapeutic interventions requires improvements in existing methods for assessing clinical status according to the severity of the pathological process, enabling more precise evaluation of disease correction. Materials and Methods: Neonatal hypoxia-ischemia was modeled in CD-1 mice at 9 days of age (n=51). Motor and coordination impairments were assessed using the inverted grid, vertical pole, and horizontal pole tests on days 7 and 14. Anxiety-like behavior and exploratory activity were evaluated in the open field test on day 15. Neurophysiological reactivity was examined by administering caffeine (20 mg/kg) one hour prior to the Open field test on day 16. Results: A statistically significant difference in motor activity was observed between the mild and moderate injury groups compared to the intact group, with reductions of 37% and 57% in the inverted grid test and 27% and 53% in the vertical pole test, respectively. Pharmacological challenge with caffeine stimulated a 1.5-fold increase in speed and distance travelled in the moderate injury group compared to those in the intact group, despite baseline statistically significant differences in the Open field test. Conclusion: The experimental approach to assessing the clinical status of animals after neonatal hypoxia-ischemia modeling, followed by stratification based on injury severity, revealed statistically significant differences across multiple parameters between the studied groups.

Introduction: Osteoporosis is an important medical and social public health problem in an aging or elderly society, the issue of pharmacological correction of which remains unresolved to this day. Materials and Methods: A design of prospective 11β-HSD1 inhibitors was performed on the basis of the literature data. A virtual screening of the designed compounds was performed using pharmacophore searching (DataWarrior, Flexophore), pharmacophore alignment (PhESA), and molecular docking (Jamda). 2D protein-ligand interaction maps were generated using PoseEdit, and 3D visualizations were produced in VMD. The cytotoxicity of the compounds was assessed in HEK-293 cells across a concentration range of 8–1024 μM, with IC50 values calculated in RStudio. Results and Discussion: A comprehensive virtual screening of prospective 11β-HSD1 inhibitors was performed, incorporating pharmacophore searching, PhESA alignment, and molecular docking against the 11β-HSD1 complex (PDB: 4YYZ). Several compounds (TS-897, TS-883, TS-945, and others) demonstrated Jamda Score values comparable to or exceeding that of the native ligand, indicating strong predicted binding affinity. Additional candidates were identified based on high pharmacophore similarity (>0.95). Among the 14 proposed compounds, four (IV-81, IV-91, IV-158) exhibited no cytotoxicity in HEK-293 cells (IC50 > 1024 µM). These findings support the potential of the synthesized azoloazine derivatives as novel 11β-HSD1 inhibitors for further in vitro and in vivo studies in osteoporosis therapy. Conclusion: As a result of this work, original azoloazine derivatives have been developed for further biological testing aimed at regulating the activity of 11β-hydroxysteroid dehydrogenase isoforms (11β-HSDs) for pharmacological correction of bone remodeling and osteoreparation disorders.

Introduction: Gene therapy for Myoshi myopathy is extremely relevant, as it may become the first pathogenetic treatment for dysferlinopathy. The aim of this study was to study the efficacy and safety of the use of a genetic construct, the AAV9-DYSF-DV3’ virus, for the treatment of limb girdle muscular dystrophy LGMD) type R2. Materials and Methods: Mouse models of limb girdle muscular dystrophy type R2 В6.А-Dysfprmd/GeneJ were used to study the effectiveness of AAV9.DYSF drug and the corresponding C57BL/6J controls were used. During the study, muscle activity was determined on the basis of the following tests: “Grip test”, “Holding an animal on a slippery surface of a vertical rod”, “Forced swimming with a load”, and ”Wire hanging”. In the course of acute and subchronic toxicity, hematological and biochemical blood tests of the rats, histological analysis and ”Open field” behavioral testing were performed. Results and Discussion: In this study, for the first time, a comprehensive investigation of the effectiveness of gene therapy using the two-vector system of adeno-associated AAV9-DYSF-DV3’ virus with overlapping DYSF cDNA sequences was conducted in a mouse model of limb girdle muscular dystrophy type 2 R. Conclusion: During the testing of the drug’s effectiveness, it was discovered that drug AAV9.DYSF showed the best effectiveness in mice with the absence of the protein dysferlin in behavioral testing at the maximum dose (5*1012) with a double intramuscular injection. In the “Grip test”, the index in В6.А-Dysfprmd/GeneJ mice increased by 29% (p=0.0026) relative to that in the K-group. In the tests “Forced swimming with a load”, ”Wire hanging”, and ”Holding an animal on a slippery surface of a vertical rod”, the indicators also improved by 80% (p=0.0019), 104.8% (p=0.001) and 20% (p=0.025), respectively, relative to those of the negative control. During acute and subchronic toxicity, the administration of the drug to animals does not cause death or intoxication.

Introduction: Beta-amyloid (Aβ) is involved in numerous physiological and pathophysiological processes and is one of the key players in the pathogenesis of Alzheimer’s disease. Aβ interacts with the 35-HAEE-38 site of the α4 subunit of the α4β2 nicotinic acetylcholine receptor. The synthetic tetrapeptide HAEE effectively inhibits the aggregation of endogenous Aβ. HAEE specifically binds to the 11-EVHH-14 site of Aβ both in the absence and presence of zinc ions, leading to the formation of stable complexes. We hypothesized that the HAEE motif could represent a universal binding site for Aβ within the human proteome. Materials and Methods: To test this hypothesis, a large-scale search for all amino acid sequences containing the HAEE motif in the human (Homo sapiens) proteome was performed using our in-house PepString server (http://pepstring.eimb.ru/). The conservation of the identified sites was analyzed across jawed vertebrates using BLAST. Protein localization and structural features were determined based on data from UniProt, PDB, and AlphaFold. Results: We identified 85 proteins (including 200 isoforms) containing the HAEE motif. Of these, 26 proteins are membrane proteins, including receptors, ion channels, and transporters (e.g., CACNA1B, MRS2, SLC15A2), and 59 are intracellular proteins, mostly nuclear transcription factors (including 13 zinc finger proteins). Structural analysis revealed that the HAEE motif is often located within functionally important domains, such as cytoplasmic loops of transmembrane proteins or DNA-binding domains. Conclusion: Given that Aβ acts as an extracellular ligand and can also penetrate various intracellular compartments, all identified proteins with the HAEE motif are considered potential physiological and pathophysiological targets for Aβ. The most promising candidates are proteins whose HAEE sites are structurally similar to that in α4β2-nAChR and/or coordinate zinc ions. These findings enhance our understanding of the molecular mechanisms of Aβ function and open new avenues for the search of therapeutic targets in AD.

5-Morpholino-substituted 2H-imidazole 1-oxides have recently proven themselves as perspective molecules to counteract the pathological states associated with endothelial dysfunction. Among this series, an enhanced pharmacological activity has previously been demonstrated by a p-fluorophenyl-substituted derivative, implying the expediency of the scope expansion with regard to the related halogen-containing molecules. Herein, we report the straightforward synthesis of 7 novel morpholino-tethered 2H-imidazole oxides featuring various haloaryl moieties in their structures with the reaction yields ranging from 40 to 87%. The in silico analysis indicated the specific affinity of the obtained compounds to phosphodiesterase 5a (PDE5a), known as a vital enzyme for the cardiovascular system functioning. At the same time, the in vitro assay on the HEK-293 cell line showed generally low toxicity of the compounds under consideration, suggesting their eligibility for the further in vivo studies.

Introduction: Osteoporosis is an significant medical and social public health problem in an aging or elderly society, the issue of pharmacological correction of which remains unresolved to this day. Materials and Methods: The rationale for this idea stems from our previous findings on the role of 11B-HSD type 2 in bone remodeling and osteoreparation, combined with a content analysis and literature review of scientific publications from PubMed, Scopus, Cyberleninka, Google Scholar, and ResearchGate. Results and Discussion: Current understanding of the molecular mechanisms of bone homeostasis allows for a significant shift and expansion in the paradigms for treating and preventing osteoporosis. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key metabolic enzyme that catalyzes the intracellular conversion of inactive glucocorticoids into physiologically active ones. Research conducted over the past decade has shown that abnormal 11β-HSD1 activity contributes to the pathogenesis of obesity, type 2 diabetes, metabolic syndrome, and osteoporosis. The scientific challenge of regulating the activity of 11β-hydroxysteroid dehydrogenase (11β-HSD) isoforms and restoring homeostasis in the 11β-HSD1/11β-HSD2 enzymatic system is proposed to be addressed through the design and application of novel azole-based heterocyclic compounds as 11β-HSD1 inhibitors. Conclusion: The development of azole-based heterocyclic 11β-HSD1 inhibitors is expected to yield promising drug candidates for pharmacologically correcting impaired bone remodeling and repair.

Introduction: Doxorubicin (DOX) is an anthracycline antibiotic with considerable significance in clinics as an anticancer agent, which is limited by its cardiotoxicity, though. A large number of possible therapeutic strategies for reducing cardiotoxicity with doxorubicin have been studied. However, none of them fully meets the requirements of clinical practice. The aim of the study: to evaluate the cardioprotective effects of a new original heterocyclic compound, a pyridine-3-carboxylic acid derivative potassium 5-hydroxynicotinate. Materials and Methods: Cardiac injury was induced by intraperitoneal administration of doxorubicin (DOX) at a dose of 20 mg/kg. After 48 hours, the parameters of left ventricular contractility and StTTI coefficient were assessed on isolated heart in the Langendorff system under the conditions of 480 beats per minute for 11 seconds. Additionally, specific markers of myocardial injury were determined. The lipid peroxidation products and SOD activity were measured as well to challenge whether the compound is able to reduce oxidative stress. Results: The study showed that pretreatment by potassium 5-hydroxynicotinate (35 mg/kg, 48 h) attenuated DOX-induced damage, resulting in a significant decrease in the StТТI coefficient to 3.3 values and in the restoration of the antioxidant activity of enzymes. Conclusion: The obtained data totally demonstrate the protective effects of potassium 5-hydroxynicotinate in DOX-induced cardiomyopathy. A significant role in potassium 5-hydroxynicotinate-mediated cardioprotection is, apparently, related to the reduction of oxidative stress and down-regulation of the level of intracellular calcium.

Тау-протеинпатия — группа нейродегенеративных заболеваний, характеризующаяся гиперфосфорилированием тау-белка вследствие посттрансляционных модификаций. Потенциальным фармакологическим веществом, который воздействует на патогенетические каскады гиперфосфорилирования тау-белка, является пептидный миметик гетерорецептора EPOR/CD131 (ARA-290). Показано, что ARA-290 изменяет параметры митохондриального дыхания, вызванные влиянием стрессоров-модуляторов. Для оценки энергетического фенотипа использовали культура нейронов мышей линии P301S, и в условиях окислительного стресса соединение ARA-290 улучшало метаболическую активность, тем самым демонстрируя свои нейропротекторные свойства. При оценке поведенческих реакций в тесте «Открытое поле» экспериментальная группа P301S с фармакологической поддержкой ARA-290 продемонстрировала быструю адаптационную способность, о чем свидетельствовали высокие показатели нахождения животных в центральной зоне арены. Таким образом, улучшение когнитивных функций подтвердилось и в результате тестирования на модели «Распознавание новых объектов», в котором отмечены высокие значения общего расстояния и средней скорости передвижения в арене, а также высокие показатели заинтересованности новым объектом и индексов предпочтения и дискриминации. Со стороны оценки двигательных функций у экспериментальной группы мышей, получавшей соединение ARA-290, обнаружены существенные отличия в более долгом времени удержании равновесия на перевернутой сетке, что свидетельствует о улучшенной координации и локомоции. В свою очередь, полученные статистически достоверные значения отличались у экспериментальной группы от групп сравнения и положительного контроля, что свидетельствует о замедленном прогрессе моторной дисфункции и координации движений у мышей трансгенной линии P301S.

Одним из возможных вариантов фармакологической поддержки при тау-протеинопатии является композиция на основе тетрапептида НАЕЕ (His-Ala-Glu-Glu, гистидил-аланил-глутамил-глутаминовая кислота), цинка и человеческого сывороточного альбумина (Hsa). В исследованиях in vitro композиция HAEE-Zn-Hsa в концентрации 1 мкм (в расчете на пептид) приводила к повышению митохондриальной функции: повышение потребления кислорода OCR от 125,32 до 179,24 пмоль/мин (p < 0,05) и снижению гликолитической активности клеток первичной смешанной культуры гиппокампа мышей P301S у самцов на 84 % и у самок на 44,6 % (p < 0,05), по сравнению с животными контрольных групп. У мышей P301S композиция HAEE-Zn-Hsa (в дозировке 0,01 мг, подкожно в течение 30 дней 1 раз в 2 дня) в тесте «Лабиринт Барнса» вызывала улучшение когнитивных функций: снижение общего расстояния пройденной дистанции на 34,5 % (p ≤ 0,0001), по сравнению с мышами положительного контроля, сокращение латентного времени нахождения на платформе в группе на 77,5 % (p ≤ 0,0001), по сравнению с мышами положительного контроля, увеличивалась скорость передвижения на данной дистанции на 36 % (p ≤ 0,0001), по сравнению с мышами положительного контроля. Применение HAEE-Zn-Hsa и пирацетама (в дозировке 200 мг, подкожно в течение 30 дней 1 раз в 2 дня), при проведении теста «Вертикальный стержень», в первой контрольно-временной точке у мышей не было выявлено статистически достоверных различий между группами, так как отсутствовали проявления симптомов тау-протеинопатии, во второй контрольно-временной точке мыши, получающие композицию HAEE-Zn-Hsa, смогли дольше удерживать равновесие на стержне на 36 % (p ≤ 0,0001), по сравнению с мышами положительного контроля, это указывает на замедление развития заболевания. В результате исследования морфологической картины тау-протеинопатии у мышей P301S с применением HAEE-Zn-Hsa и мышей линии C57Bl/6 были обнаружены сходные особенности в энторинальной коре головного мозга, где нейроны имели преимущественно округлую и пирамидальную форму с везикулярными ядрами. В гиппокампе мышей данных групп наблюдался плотный зернистый ряд нейронов с однонаправленными отростками.

Introduction: Elevated intraocular pressure (IOP) has been identified as a major risk factor for the progression of primary open-angle glaucoma (POAG). However, the continued progression of POAG in some patients, despite the successful IOP reduction, indicates that IOP-independent mechanisms contribute to the development of optical neuropathy. Thus, it is relevant to further determine the molecular mechanisms of retinal ganglion cells (RGCs) death in order to develop therapeutic approaches independent of IOP in order to stop the progression of the disease. The aim: to research the correction possibility of experimental POAG induced by intracameral (i.c.) administration of hyaluronic acid using 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyltaurinate. Materials and Methods: The study of the correction of neuroretinal changes on a model of POAG was carried out on Wistar rats. In order to correct POAG, 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyltaurinate (EHMP-NAT) was used at doses of 27.5 mg/kg intramuscularly (i.m.) and 0.5 mg/kg instillationally. Further, the effectiveness of the combination of timolol eye drops with i.m. EHMP-NAT was studied. The effectiveness of the studied agents was evaluated on the 67th day of the experiment using ophthalmoscopic semi-quantitative assessment of the fundus condition, ocular tonometry, estimation of oxidative stress markers and markers involved in retinal apoptosis pathway using enzyme-linked immunosorbent assay (ELISA). Results: On the model of POAG, it was shown that 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyltaurinate with the laboratory code EHMP-NAT has a pronounced neuro-, retinoprotective action based on the data of ophthalmoscopy, semi-quantitative assessment of the fundus condition, ocular tonometry, estimation of oxidative stress markers (GSH, CAT, SOD) and markers involved in retinal apoptosis (BAX, BCL-2, Caspase-3). On the 67th day of the experiment, the results of a comprehensive analysis revealed that the combination of EHMP-NAT 27.5 mg/kg i.m. + timolol 0.04 mg/kg instillationally has a more pronounced protective effect than EHMP-NAT 27.5 mg/kg i.m. in monotherapy in the POAG model. Conclusion: The data obtained indicate the need for the combined use of drugs with a hypotensive effect to normalize IOP with neuroretinoprotective agents in the correction of POAG.

Introduction: The use of atomic force microscopy (AFM) to investigate membrane stiffness in neurons provides valuable insights into cellular mechanisms and their alterations in response to various pathophysiological conditions. Heat shock protein HSP 70, a component of the cellular stress response system, plays a role in stabilizing the protein structures of cellular organelles. However, studies examining changes in the stiffness of hippocampal neuronal membranes in its presence, particularly following cerebral circulation disturbances, have not been conducted yet. Materials and Methods: The study was performed on a mixed culture of hippocampal neurons derived from 9-day-old male CD-1 mice, obtained 24 hours after modeling neonatal hypoxia-ischemia. The following groups were formed: Intact culture; HI culture; HI + rhHSP70 10-6 M; HI + rhHSP70 10-8 M; HI + rhHSP70 10-9 M; HI + rhHSP70 10-12 M, with the substance added in dilutions from an initial dose of 0.1 µg/g. The Young's modulus was measured using force spectroscopy, and maps of local stiffness of various surface areas were generated. Results and Discussion: The neonatal hypoxia-ischemia model resulted in an 18% increase in the stiffness of the neuronal cell surface compared to the control group (p<0.001). The addition of rhHSP70 at concentrations of 10-6 M and 10-8 M to the HI culture led to an increase in membrane stiffness by 20% (p<0.001) and 3% (p<0.0034), respectively, while dilutions of rhHSP70 at 10-9 M and 10-12 M resulted in a decrease in membrane stiffness by 35% (p<0.001) and 22% (p<0.001) compared to the intact group, respectively. In comparison to such in the neuronal culture group after neonatal hypoxia-ischemia modeling, membrane stiffness with the addition of rhHSP70 at 10-8 M, 10-9 M, and 10^-12 M decreased by 17% (p<0.0004), 65% (p<0.001), and 49% (p<0.001), respectively. Conclusion: Thus, the addition of rhHSP 70 results in a reduction in membrane stiffness in the mixed culture of hippocampal neurons in mice, compared to the intact culture obtained after neonatal hypoxia-ischemia. The AFM method allows for the assessment of how various molecules, such as heat shock proteins (e.g., rhHSP70), influence the mechanical properties of membranes, which may be critically important for the development of new therapeutic agents.

Introduction: The aim of this study was to evaluate the processes of bone remodeling and osteoreparation in modeling femoral fracture in mice with zero expression of 11β-HSD2 (11β-HSD2-/-) or both 11β-HSD2 and apolipoprotein e (11β-HSD2-/-/ApoE-/-). Materials and Methods: The experimental study was conducted on 60 male mice weighing 24-30 g. The study used male mice that lacked the expression of 11β-HSD2 (knockout mice with the Hsd2-/- genotype) and male mice that lacked the expression of 11β-HSD2 and apolipoprotein E (double knockout mice with the Hsd2-/-/ApoE-/- genotype). The control group includes wild type C57bl/6 animals. Modeling of a fracture of the proximal metaphysis of the femur was performed in animals at the age of 6 months using a closed technique. Fracture fusion and bone remodeling and osteoreparation processes were evaluated 6 weeks after fracture modeling. Results and Discussion: It has been shown that a violation of the regulation of steroid hormone metabolism in groups of animals with the Hsd2-/- and Hsd2-/-/ApoE-/- genotypes leads to an increase in the number of ungrown fractures by 3 and 3.5 times, respectively, in comparison with wild-type animals. It was found that the microcirculation level of the proximal metaphysis of the left femur in the area of the formed bone callus in the group of animals with the genotype 11β-HSD2-/- significantly decreased from 92.075±4.33 perfusion units (PE) in the group of wild-type animals to 82.67±3.54 PE (p=0.0002) in the group of animals with the genotype HSD2-/- and up to 75.85±5.64 (p<0.0001) in the group of mice with the Hsd2-/-/ApoE-/- genotype. When calculating the coefficient of endothelial dysfunction, an increase in the coefficient of endothelial dysfunction was found from 1.297±0.19 in intact animals to 2.115±0.45 (p<0.00001) in the group of mice with the Hsd2-/- genotype and to 2.41±0.04 (p<0.00001) in the group of mice with the Hsd2-/-/ApoE-/- genotype. In animals with impaired cortisol metabolism, there was a slowdown in the formation of bone tissue in the fracture area, bone trabeculae had a smaller width, large amounts of fibrous and connective tissue were observed in the lumen between bone fragments, and an increase in intertrabecular spaces was noted Conclusion: The close relationship between the metabolism of 11β-HSD2 and NO, confirmed in this study, can be considered as a promising pharmacotherapeutic target. It is obvious that approaches to changing the activity of 11β-HSD have significant therapeutic potential in the treatment of osteoporosis, bone remodeling disorders and osteoreparation in fractures against the background of formed osteoporotic changes in the violation of steroid hormone metabolism.

Alzheimer’s disease (AD) is the most common proteinopathy, which is accompanied by a steady decrease in the patient’s cognitive functions with a simultaneous accumulation of amyloid plaques in brain tissues. Amyloid plaques are extracellular aggregates of amyloid β (Aβ) and are associated with neuroinflammation and neurodegeneration. Unlike humans and all other mammals, rats and mice do not reproduce AD-like pathology because there are three amino acid substitutions in their Aβ. Amyloid plaques form in the brains of transgenic mice with overexpression of human Aβ, and such mice are therefore possible to use in biomedicine to model the key features of AD. The transgenic mouse line APPswe/PS1dE9 is widely used as an animal model to study the molecular mechanisms of AD. A study was made to characterize the APPswe/PS1dE9/Blg subline, which was obtained by crossing APPswe/PS1dE9 mice on a CH3 genetic background with C57Bl6/Chg mice. No difference in offspring’s survival and fertility was observed in the subline compared to wild-type control mice. Histological analysis of the brain in the APPswe/PS1dE9/Blg line confirmed the main neuromorphological features of AD and showed that amyloid plaques progressively increase in number and size during aging. The APPswe/PS1dE9/Blg line was assumed to provide a convenient model for developing therapeutic strategies to slow down AD progression.

A marketing study of the Russian pharmaceutical market of food products with the addition of milk proteins was carried out. The study revealed that the leading position in the Russian pharmaceutical market is occupied by products for artificial nutrition, which is 37.91%; diet food - 29.95%; in the form of soy-protein cocktails - 7.11%; for sports nutrition - 5.69%; complementary foods - 5.69%. Other food products with the addition of milk proteins account for 13.74% of the total assortment. In particular, the smallest amount is occupied by products for medical nutrition intended for children with phenylketonuria aged from 1 year - 0.47%; protein-energy cocktails to support a weakened body - 1.42%; specialized products of children's dietary (therapeutic) nutrition for children from 0 to 1 year old, patients with type 1 glutaric aciduria - 2.36%.