Susanna Sergeevna Sologova

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.

Background/Objectives: Vancomycin remains a cornerstone antibiotic for Gram-positive infections, but its narrow therapeutic window and marked pharmacokinetic variability in critical patients complicate dosing. This study aimed to analyze survival and identify factors associated with mortality in intensive care unit (ICU) patients receiving vancomycin under therapeutic drug monitoring (TDM). Methods: A single-center, retrospective cohort study was conducted at City Clinical Hospital named after I.V. Davydovsky (Moscow, Russia) between December 2021 and January 2026 (IRB protocol VANCO-2021). A total of 190 adult patients from surgical, therapeutic, and cardiac ICUs receiving vancomycin for at least 3–5 days were analyzed; trough concentrations were determined by HPLC-MS/MS. Cox proportional hazards, spline Cox, and segmented (piecewise) Cox models were applied to identify mortality predictors, with bootstrap subsampling assessing threshold robustness. Results: Three independent predictors of mortality were identified: ln(minimum vancomycin concentration) (HR = 1.644, p = 0.028), age (HR = 1.019, p = 0.037), and serum creatinine (HR = 1.004, p < 0.001). A data-driven threshold trough concentration (Ctrough) of 25.5 µg/mL was identified, above which mortality increased substantially (63.0% vs. 26.4%; p < 0.05). The adjusted hazard ratio for Ctrough ≥ 25.5 µg/mL was approximately 1.88 (p = 0.054); bootstrap subsampling yielded an uncertainty interval of 23.2–33.6 µg/mL. Conclusions: Elevated minimum vancomycin concentrations exceeding 25.5 µg/mL are independently and statistically associated with increased mortality in ICU patients, likely reflecting altered drug exposure and illness severity rather than a direct causal effect. Systematic TDM is essential for maintaining vancomycin within the therapeutic range.

Local drug delivery increasingly relies on injectable hydrogels that form directly at the x‘administration site, among which light-cured systems are of particular interest: irradiation converts a liquid precursor into a depot and can trigger drug release with high spatiotemporal resolution. The aim of this critical narrative review is to systematize the key design elements of such systems and to assess their path toward the clinic. We analyze the mechanisms of photoactivation, the role of wavelength, the natural, synthetic, and hybrid polymer matrices together with their tuning parameters, and the photoinitiators. The clinical and preclinical experience in dentistry, ophthalmology, regenerative medicine, and oncology is then considered separately. Finally, we address standardization through the Quality by Design concept. We show that, despite an extensive preclinical base, no photocrosslinkable injectable depot for drug delivery has yet been approved, whereas photopolymerization itself and the photoinitiators employed are already accepted in the clinic in adjacent fields. We conclude that clinical translation is defined by three tractable tasks: qualifying photoinitiators for the injectable route of administration, overcoming the limited depth of light activation, and standardizing characterization on the basis of Quality by Design.

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/Objectives: Modern dentistry increasingly requires biomaterials that not only replace damaged tissues but also actively regulate healing processes, modulate inflammation, and provide controlled delivery of therapeutic agents under the complex physicochemical conditions of the oral cavity. This review aims to analyze the potential of PCHs, particularly methacryloyl gelatin (GelMA), as multifunctional platforms for drug delivery in dental applications. Methods: This review provides a structured narrative synthesis of the literature, focusing on the physicochemical, biological, and translational aspects of photocrosslinkable hydrogels in dentistry. Special attention was given to the key functional requirements for hydrogels used in dentistry, including adhesion in a wet environment, antimicrobial properties, and the ability to provide sustained and localized release of active compounds. Natural, synthetic, and semi-synthetic polymers were comparatively evaluated to justify the selection of GelMA as a leading platform due to its tunable mechanical properties, biocompatibility, and photopolymerization capacity. The review also analyzes mechanisms of drug release activation and provides a comparative assessment of commonly used photoinitiators, including Irgacure 2959, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and camphorquinone, with emphasis on their cytocompatibility with oral tissues. Results: Applications of these hydrogels in endodontics, periodontology, peri-implantitis therapy, and regeneration of bone and dental pulp are summarized. Conclusions: Overall, photocrosslinkable GelMA-based hydrogels (PC-GelMA) represent promising multifunctional platforms for localized drug delivery and regenerative strategies in modern dentistry.

Background. Enzyme replacement drugs for treatment of mucopolysaccharidosis type II (MPS II) do not penetrate the blood-brain barrier, significantly reducing their efficacy in patients with neuropathic form. Verenafusp alfa (Clotilia®) is a recombinant fusion protein of iduronate-2-sulfatase and a monoclonal antibody Fab fragment to human insulin receptor for distribution of the enzyme into brain. Aim. To evaluate safety, tolerability, and pharmacokinetic parameters of verenafusp alfa after single intravenous administration of escalating doses in healthy volunteers. Materials and methods. This open-label, multicohort study included 20 healthy male volunteers aged 18 to 47 years (26.1±7.8 years). Verenafusp alfa was administered intravenously for 3 hours at single doses of 0.3 mg/kg (n=1), 0.5 mg/kg (n=1), 1 mg/kg (n=6), 2 mg/kg (n=6), and 3 mg/kg (n=6). Safety was assessed based on the incidence of clinical and laboratory adverse events (AEs) and their relationship to the investigational medicinal product. Pharmacokinetic parameters were calculated using a noncompartmental method. Results. All 20 volunteers completed the study. AEs reported in 6 (30%) volunteers were mild in severity and related to changes in individual laboratory and instrumental test data. One AE (increased bilirubin level) was possibly related to the study drug. Pharmacokinetic analysis demonstrated a dose-dependent increase in maximum concentration (Cmax) from 197.60 (0.3 mg/kg) to 10,225.80 ng/mL (3 mg/kg) and area under the concentration-time curve (AUC) from 38,678.60 to 2,714,067.42 ng×min/mL respectively. The half-life ranged from 86.69 to 213.42 minutes, and clearance lowered with the increasing dose from 7.67 to 1.11 mL/min/kg. Conclusion. Single intravenous administration of verenafusp alfa at doses ranging from 0.3 to 3 mg/kg demonstrated a favorable safety profile and good tolerability in healthy volunteers. The drug's pharmacokinetics was nonlinear, with a dose-dependent increase in Cmax and AUC with the dose increment. Volume of distribution volume lowered with increase of the dose.

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.

Introduction. The use of synthetic drugs is associated with a number of side effects. When choosing a therapy to correct symptoms and treat dental diseases such as stomatitis, periodontitis, gingivitis, cheilitis, it is preferable to use herbal medicines in combination with traditional therapy, which would improve the resistance of periodontal tissues to pathogenic microorganisms. Herbal preparations are highly effective and well tolerated, which allows them to be used in modern medicine.Aim. To develop a medicinal collection with antimicrobial, anti-inflammatory, and wound-healing effects.Materials and methods. The following substances and reagents were used as research materials: Achilleae millefolii herba, Bidentis tripartitaе herba, Alni fructus, Anisi vulgaris fructus in a ratio of 1 : 1 : 1 : 1, diclofenac sodium, ascorbic acid, phosphate buffer, sodium citrate, luminol, iron (II) sulfate, heparinized blood, zymosan, saline solution, 2 % formalin solution, 10 % neutral formalin solution, hematoxylin, eosin. Antimicrobial activity was studied by comparing growth retardation of pathogenic microorganisms, antioxidant activity was studied on a chemoluminometer HLM-003 (Russia), hematological tests on mice were carried out using the ImageJ software package, Sysmex KX-21N (Sysmex, Japan), Leica RM 2145 microscope (Leica Biosystems Nussloch GmbH, Germany), binocular microscope Leica CME (Leica Biosystems Nussloch GmbH, Germany).Results and discussion. The evaluation of the anti-inflammatory, antioxidant, wound healing and antimicrobial activities of the plant herbal mixture was carried out. According to the results of the experiment, it was found that the herbal mixture has moderate antioxidant, wound healing and pronounced anti-inflammatory activity comparable to the comparison drug.Conclusion. A herbal mixture has been developed that has anti-inflammatory, antimicrobial and regenerating effects.

(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.