Ekaterina Mikhailovna Grigorevskikh

Background/Objectives: MEK inhibitors (selumetinib, mirdametinib) are the only approved class of targeted therapy for neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN), producing partial responses in a substantial proportion of patients (up to 63.6% in adults; objective response rate 19.7% versus 5.4% with placebo in the KOMET trial). Responses, however, are rarely complete or durable, and in malignant peripheral nerve sheath tumor (MPNST) single-agent MEK inhibition is clinically ineffective. Mechanisms of escape from MEK inhibition in these tumors remain poorly characterized and are reported in the literature as isolated primary studies without an integrative analysis. The aim of this review was to systematize both the established molecular mechanisms of resistance to MEK inhibitors in PN and MPNST and the biologically plausible candidate mechanisms extrapolated from other RAS-driven malignancies. Methods: This is a narrative review. A structured search was performed in PubMed, PubMed Central, NCBI Bookshelf, and Scopus, supplemented by clinical practice guidelines and regulatory documents; it covered publications up to 31 May 2026 and was updated in August 2026. Ninety-six sources are cited, and their composition by publication type is reported; record counts at the intermediate screening steps were not maintained, and no PRISMA flow diagram is presented. Results: Mechanisms were classified within a convergent framework into six categories: reactivation of MAPK signaling within the cascade; parallel (bypass) reactivation through receptor tyrosine kinases and adjacent inputs; epigenetic and transcriptional rewiring; cell survival programs; the tumor microenvironment and immune evasion; and intratumoural heterogeneity. Each mechanism was then graded along two independent axes—the strength of evidence that it confers resistance in PN or MPNST (E1–E3) and its therapeutic tractability (T1–T3)—and annotated with the entity and model constituting its evidence source. Conclusions: Resistance to MEK inhibition in PN and MPNST is convergent rather than mechanism-unique. The principal limitation of the field is the near-absence of clinical resistance data from patients progressing on MEK inhibitors; prospective molecular monitoring, rational combination trials, and mechanism-stratifying biomarkers are the priorities.

The aim. To develop a method for in vitro cultivation of Corti’s organ explants using polyethyleneimine (PEI) as an adhesive substrate. The study evaluated the potential of PEI as an effective alternative to existing substrates for in vitro cultivation of inner ear samples. Materials and methods. Explants of Corti’s organ from newborn mice (P1–P2) were used. Glass culture surfaces were treated with a PEI solution followed by treatment with fetal bovine serum. To assess the suitability of the developed explant model for ototoxicity studies, treatment with gentamicin was performed. Isoliquiritigenin was used as an otoprotector. Morphological analysis of images obtained by confocal fluorescence microscopy was conducted. The survival of hair cells after staining with phalloidin labeled with Alexa Fluor 488 was evaluated. The magnitude of stereociliary angles of outer hair cells was assessed. Results. PEI- coating provided reliable fixation of Corti’s organ explants (up to 72 h) without signs of detachment from the culture surface. The samples maintained their attachment strength through two media changes and subsequent 16 washing cycles during fluorescent staining. Morphological analysis of the control group revealed no signs of toxic effects of PEI on hair cells. The organotypic model using PEI coating reproduced the classic pattern of gentamicin-induced ototoxicity with a basal-apical gradient of damage. For the first time, this model demonstrated the otoprotective effect of isoliquiritigenin (1 μM) against gentamicin-induced ototoxicity (500 μM), most pronounced in the middle turn of the cochlea for both inner and outer hair cells ( p < 0.0001 for both comparisons with the gentamicin group). Conclusion . The efficacy of PEI as an alternative substrate for cultivating inner ear samples has been demonstrated for the first time, showing optimal adhesive properties and no inherent toxicity. The developed method represents a promising approach for ototoxicity research and otoprotector screening.

The study presents data justifying the composition of a combined herbal blend to improve men’s health, based on three types of medicinal plant materials: puncturevine (Tribulus terrestris), alfalfa (Medicago sativa), and field penny‑cress (Thlaspi arvense), as well as trace elements. The aim of the study is to summarize available literature on the chemical composition, pharmacological properties, and primary uses of the components of the herbal blend. Materials and methods. A review of publications over the past 40 years was conducted in peer‑reviewed databases to identify trends in the use of the studied plants for the prevention and treatment of conditions related to men’s health. Results. Tribulus terrestris (puncturevine) exhibits adaptogenic, anabolic, and antioxidant activity and improves sperm motility and viability. Medicago sativa (alfalfa) contains saponins, flavonoids, phytoestrogens, and a complex of vitamins; it stimulates spermatogenesis, increases testosterone levels, and has anti‑inflammatory and hypolipidemic effects. Thlaspi arvense (field penny‑cress) enhances fertility, improves semen quality, and demonstrates membrane‑protective and antioxidant effects. The role of trace elements (iron, copper, manganese, zinc) in supporting male reproductive function is justified from a physiological and biochemical perspective. An optimized composition of the herbal blend is proposed, including daily doses of plant components and trace elements. Conclusion. The developed herbal blend has a comprehensive positive effect on androgenic status and spermatogenesis, exhibits antioxidant and hypolipidemic properties, and can be used in andrological practice as well as a dietary supplement for athletes and individuals leading an active lifestyle.

Background: Tooth extraction is often accompanied by bone tissue loss. This systematic review aims to compare osteoplastic materials for socket preservation. Methods: This systematic review was carried out with the PRISMA statement. To identify relevant studies, a thorough literature search was executed in several databases, such as Medline, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. The inclusion criteria were restricted to randomized controlled trials, and their methodological quality was evaluated with the Cochrane Risk of Bias tool (ROB 2). Results: Based on the predefined inclusion and exclusion criteria, nine randomized clinical trials published before 2024 were selected for analysis, all of them investigating the application of osteoplastic materials. Six studies performed xenogenic bone augmentation; one of them compared alloplastic and xenogenic materials; two studies described synthetic osteoplastic materials; and one described autogenic bone material. Conclusion: Socket augmentation with osteoplastic materials demonstrates effectiveness in preserving alveolar ridge dimensions and creating favorable conditions for further implant placement, though differences in clinical performance highlight the need for careful material selection.

The relationship between the influence of the brain-derived neurotrophic factor (BDNF) on the development of alcoholism and possible ways of using this molecule or related compounds (mimetics) as targets of anti-addictive action are discusses in the article.The aim of the work was to carry out a literature review to identify potential applications of the BDNF signaling pathways to assess the feasibility of developing new drugs.Materials and Methods. The following abstract databases were used to search for the information materials: PubMed, EMBASE, ResearchGate, elibrary.ru. The key queries for the search included the following ones: ‘BDNF’, “BDNF TrkB”, “BDNF LNGFR”, “alcoholism therapy”, “anti-addiction drugs”, “signaling pathways”, “alcoholism”, “ethanol”, “poisoning”. The depth of the search was 40 years (1985–2025). The total number of the sources included in the review is 116.Results. This study analyzed the molecular mechanisms of the action of BDNF, including its biosynthesis, structural forms (BDNF and pro-BDNF), and functions and features of TrkB and LNGFR receptors. These receptors play a key role in the regulation of the neuronal plasticity, a neuronal survival and apoptotic processes. The performed review of the scientific literature made it possible to establish that at least 9 chemical compounds with a potential anti-addictive activity that affect the receptors and signaling cascades associated with BDNF, have been identified as of 2025. Based on the data obtained, a hypothesis about the prospective use of BDNF and its signaling pathways as potential targets for developing new pharmacological agents aimed at the treatment of alcohol dependence, have been formulated. The established facts can significantly expand the therapeutic opportunities in the fight against the alcoholic dependence and associated neurotoxic conditions.Conclusion. At least 9 compounds with a potential anti-addictive activity associated with a mimetic effect on the receptors and signaling pathways of the BDNF molecule have been analyzed and found to exist as of 2025.

(1) Background: Impacted third molar extraction with a scalpel and rotary instruments is one of the most traumatic surgeries in dentistry. Therefore, it is necessary to discover less traumatic methods and instruments to reduce the risk of postoperative complications. (2) Methods: This study is reported in accordance with the CONSORT guidelines. The study aim is to assess the effectiveness of an Er:YAG laser with a wavelength of 2.94 μm, cutting and rotating instruments in the extraction of lower third molars in comparison with the traditional instruments using clinical and radiology parameters. In the control group, the impacted third molars were extracted with the traditional instruments, like scalpel and rotary instruments; in the test group, the impacted third molars were extracted with an Er:YAG laser. As per the inclusion and exclusion criteria, we enrolled 60 patients who were randomly assigned into two groups (Er:YAG laser group and control group). The efficacy of the Er:YAG laser was assessed by postoperative pain, collateral swelling, mouth opening, and radiology parameters such as radiographic infrabony defects and radiographic bone height after tooth extraction. (3) Results: The results showed that the clinical postoperative parameters like pain, collateral swelling, and mouth opening were less pronounced in the Er:YAG laser group than those in the control group (p < 0.001). According to the data of the radiology parameters (RBH and RID), the regeneration of the socket after extraction was better in the laser group than in the control group (p < 0.001). (4) Conclusions: Based on the obtained results of clinical and radiology parameters assessment, it was shown that third molar extraction using an Er:YAG laser is a less traumatic method than extraction using a scalpel and rotary instruments.

To assess the pharmacological safety of the dipeptide mimetic of the 2nd loop of BDNF (compound GTS-201) when co-administered with ethanol, its effect on the alteration in motor activity induced by ethanol during acute and subchronic administration in mice C57Bl/6 and DBA/2 was studied. It was found that GTS-201 at a dose of 5.0 mg / kg, i.p., without affecting spontaneous motor activity per se, after a preliminary acute administration prevented the development of a sedative reaction caused by ethanol (2.0 g/ kg, i.p.) in C57Bl/6 mice. After subchronic administration, GTS-201 is devoid of psychostimulant effect and impact on the formation of ethanol-induced behavioral sensitization in DBA/2 mice. The data obtained indicate the absence of a psychostimulant component and synergism in the pharmacological profile of GTS-201 when used with ethanol at low dose.

The most common primary malignant brain tumors in adults are gliomas. Glioblastoma is the most prevalent and aggressive tumor subtype of glioma. Current standards for the treatment of glioblastoma include a combination of surgical, radiation, and drug therapy methods. The drug therapy currently includes temozolomide (TMZ), an alkylating agent, and bevacizumab, a recombinant monoclonal IgG1 antibody that selectively binds to and inhibits the biological activity of vascular endothelial growth factor. Supplementation of glioblastoma radiation therapy with TMZ increased patient survival from 12.1 to 14.6 months. The specificity of TMZ effect on brain tumors is largely determined by special aspects of its pharmacokinetics. TMZ is an orally bioavailable prodrug, which is well absorbed from the gastrointestinal tract and is converted to its active alkylating metabolite 5-(3-methyl triazen-1-yl)imidazole-4-carbozamide (MTIC) spontaneously in physiological condition that does not require hepatic involvement. MTIC produced in the plasma is not able to cross the BBB and is formed locally in the brain. A promising way to increase the effectiveness of TMZ chemotherapy for glioblastoma is to prevent its hydrolysis in peripheral tissues and thereby increase the drug concentration in the brain that nanoscale delivery systems can provide. The review discusses possible ways to increase the efficacy of TMZ using nanocarriers.

(1) Background: Antibiotics are used in every medical field including dentistry, where they are used for the prevention of postoperative complications in routine clinical practice during the third molar extraction. (2) Methods: This study is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The present systematic review aimed to evaluate and systematize the use of antibacterial drugs in order to prevent postoperative complications in outpatient oral surgery for wisdom teeth extraction. We conducted a systematic review using electronic databases such as Medline PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. Considering inclusion and exclusion criteria, we included randomized clinical trials published up to 2021 investigating the antibiotic prescription for third molar extraction. (3) Results: We selected 10 studies after the application of inclusion and exclusion criteria. The results showed that the most widely used antibiotic was amoxicillin both with and without clavulanic acid, in different dosages and duration. There were no statistically significant differences between treatment groups for development of postoperative complications. (4) Conclusions: Based on the analysis of the included studies, penicillin is currently the most widely prescribed group of antibiotics. The widespread use of this antibiotic group can lead to antimicrobial resistance (AMR). Due to increasing prevalence of bacteria resistance to penicillins, clinicians should carefully prescribe these antibiotics and be aware that the widespread use of amoxicillin may do more harm than good for the population.

The forced massive transition of universities to distance learning due to the pandemic has raised questions about the effectiveness of online education in general and video lectures in particular. Research shows that video lectures are either comparable or less effective than face-to-face lectures. In this work, based on the data collected as part of the experiment, we compare two lecture formats (videolecture and face-to-face lecture) based on the educational results of students, and also evaluate the combined lecture format. The experiment involved 151 second-year students in the direction of training “Pharmacy” of Sechenov University. The field experiment was carried out in the spring semester of the 2020-2021 academic year in three stages. At the first stage, some of the students listened to a face-to-face lecture, and some - a video lecture. At the second stage, both groups were swapped. At the final stage, both groups listened to a combined lecture. Our research has shown that a video lecture and a face-to-face lecture are the same in their effectiveness: on average, students received the same educational results as a result of mastering the lecture material. At the same time, the combined lecture led to an increase in the educational results of students - after the combined lecture format, students received a higher score for the post-test, and also showed a greater increase in the level of knowledge. The results of the study will be especially relevant for the administration of universities responsible for the implementation of online learning, and teachers who conduct lectures.