(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.

We studied the anti-anxiety effect of a low-molecular-weight mimetic of the BDNF loop 2, hexamethylenediamide bis-(-N-hexanoyl-L-seryl-L-lysine) (GTS-201) in adult animals. GTS-201 at a dose of 5 mg/kg after acute intraperitoneal administration to outbred male and female rats increased the time spent in the open arms and the number of entries into the open arms in the elevated plus maze (EPM). In "highly emotional" male BALB/c mice, GTS-201 exhibited a dose-dependent anxiolytic effect in the EPM in a dose range of 0.5-2.0 mg/kg with a maximum effective dose of 1 mg/kg. These data confirm the previously revealed anti-anxiety properties of GTS-201 in inbred male and female BALB/c mice and rats and indicate the dependence of the pharmacological activity of the BDNF mimetic on animal age.

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.

РезюмеАктуальность: Сложный и динамичный процесс ранозаживления включает стадии воспаления, пролиферации и созревания соединительной ткани рубца.На каждом из этапов ремоделирования раны цинк как эссенциальный микроэлемент играет важную физиологическую роль.Цинк увеличивает миграцию и пролиферацию кератиноцитов, участвует в реэпителизации эпидермиса, обладает противовоспалительным, антиоксидантным, иммуномодулирующим и антимикробным действием.Цель исследования: Сравнительное изучение влияния комплекса цинка производного N-изопропенилимидазола под шифром Пилим-1 на течение раневого неинфицированного процесса при моделировании плоскостной кожной раны у крыс

(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 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.

Epigenetic regulation by microRNAs (miRs) demonstrated a promising therapeutic potential of these molecules to regulate genetic activity in different cancers, including colorectal cancers (CRCs). The RNA-based therapy does not change genetic codes in tumor cells but can silence oncogenes and/or reactivate inhibited tumor suppressor genes. In many cancers, specific miRs were shown to promote or stop tumor progression. Among confirmed and powerful epigenetic regulators of colon carcinogenesis and development of resistance are onco-miRs, which include let-7, miR-21, miR-22, miR-23a, miR-27a, miR-34, miR-92, miR-96, miR-125b, miR-135b, miR-182, miR-200c, miR-203, miR-221, miR-421, miR-451, and others. Moreover, various tumor-suppressor miRs (miR-15b-5b, miR-18a, miR-20b, miR-22, miR-96, miR-139-5p, miR-145, miR-149, miR-197, miR-199b, miR-203, miR-214, miR-218, miR-320, miR-375-3p, miR-409-3p, miR-450b-5p, miR-494, miR-577, miR-874, and others) were found silenced in drug-resistant CRCs. Re-expression of tumor suppressor miR is complicated by the chemical nature of miRs that are not long-lasting compounds and require protection from the enzymatic degradation. Several recent studies explored application of miRs using nanocarrier complexes. This study critically describes the most successfully tested nanoparticle complexes used for intracellular delivery of nuclear acids and miRs, including micelles, liposomes, inorganic and polymeric NPs, dendrimers, and aptamers. Nanocarriers shield incorporated miRs and improve the agent stability in circulation. Attachment of antibodies and/or specific peptide or ligands facilitates cell-targeted miR delivery. Addressing in vivo challenges, a broad spectrum of non-toxic materials has been tested and indicated reliable advantages of lipid-based (lipoplexes) and polymer-based liposomes. Recent cutting-edge developments indicated that lipid-based complexes with multiple cargo, including several miRs, are the most effective approach to eradicate drug-resistant tumors. Focusing on CRC-specific miRs, this review provides a guidance and insights towards the most promising direction to achieve dramatic reduction in tumor growth and metastasis using miR-nanocarrier complexes.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family with diverse psychopharmacological effects including antidepressant and anxiolytic actions. However, the clinical use of BDNF is limited due to its poor pharmacokinetic properties. The development of low-molecular-weight BDNF mimetics passing through the blood-brain barrier is an emerging strategy for improved managing psychiatric diseases. The present study characterizes a novel dipeptide mimetic of the 2nd BDNF loop named GTS-201, which exhibits psychotropic properties in experimental animal models of anxiety and alcohol dependence. The aim of this work was to study the pharmacokinetics of GTS-201 in rats at a saturating dosage of 5 mg/kg applied by the intraperitoneal route and to characterize the effects on neurotransmitter levels in the blood and brain. The maximum concentration (Cmax) of GTS-201 in the plasma (867 ± 69 ng/ml) was recorded at 35 ± 7.7 min after administration (Tmax) with a half-elimination period (T1/2) of 19.5 ± 1.8 min, while in the brain tissue Cmax was 14.92 ± 3.11 ng/ml, Tmax was 40.0 ± 7.7 min and T1/2 were 87.5 ± 12.7 min. The relative tissue availability of the GTS-201 for the brain reached 2.9%. At the dose applied, GTS-201 induced a significant increase of serotonin (5-fold) and dopamine levels in the brain tissue (8-fold) along with a decrease in cortisol content in blood plasma 45 min after acute administration. In summary, GTS-201 crosses the blood-brain barrier after acute administration and affects the activity of serotonergic and dopaminergic systems, which may underlie its neuropsychotropic effects described previously.

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.

The study examined the effect of GTS-201, a low-molecular weight mimetic of brain-derived neurotrophic factor (BDNF) loop 2, on persistent alcohol craving in outbred male and female albino rats with ethanol preference score ~50% developed in the free choice paradigm between 10% ethanol and water over 24 weeks. Both single and subchronic (5 days) injections of GTS-201 in a daily dose of 5 μg/kg reduced alcohol deprivation effect in female, but not in male rats. The possibility of in vivo sex-dependent regulation of modeled alcohol craving with a low-molecular-weight dipeptide mimetic of BDNF loop 2 was demonstrated and sex-related differences in this effect were revealed

Pain is an important signal of almost all pathological processes. At the same time, in the presence of painful sensations, a person tried to eliminate them to improve the quality of life. Therefore, at all times, painkillers are played a very important role in the pharmaceutical market. The search for new molecules with analgesic properties and the development of dosage forms for already acting drugs are still important tasks in the pharmaceutical environment. In this review, we tried to show development path of the search for a new painkillers.

Ранее было показано,что миметик 4-й петли мозгового нейротрофического фактора (BDNF) ГСБ-106при взаимодействии с TrkB рецепторами активируетпострецепторные сигнальные пути (PI3K/AKT и МАРК/ERK1/2) и проявляет анксиолитическую активность [1].Синтезированный в НИИ фармакологии имени В.В.Закусова миметик 2 й петли BDNF (ГТС 201)на культуре клеток активировалтолько МАРК/ERK1/2 путь.Целью исследования было изучение возможного анксиолитического действия ГТС-201 в опытах invivo.Эксперименты выполнены на беспородных половозрелых мышах самцах CD-1 и на инбредных мышах-самцах линии BALB/cс выраженной тревожной реакцией на эмоциональный стресс.Оценку тревожного поведения проводили в тесте «приподнятый крестообразный лабиринт» (ПКЛ, ООО «Открытая наука»), спонтанную двигательную активность регистрировали с помощью актометра(Opto-Varimex, США).Увеличение времени нахождения в открытых рукавах при отсутствии изменений двигательной активности рассматривали как проявление анксиолитического эффекта.Статистическую обработку полученных результатов проводили с использованием однофакторного дисперсионного анализа (ANOVA) и t-критерия Стьюдента (α=0.05).При изучении противотревожного действия ГТС-201 в диапазоне доз 0,1-5,0 мг/кг, в/б, в тесте ПКЛ установлено, что у мышей CD-1 миметик дозозависимов дозе 1,0 мг/кг увеличивал число выходов в открытые рукава по сравнению с контрольной группой (1,7±0,5 vs0,5 ± 0,2, p≤0,05), не влияя на общую двигательную активность животных.У мышей BALB/cГТС-201 в дозах 0,5 и 1,0 мг/кг, в/б, статистически значимо увеличивал время пребывания в открытых рукавах лабиринта по сравнению с контрольной группой в 2,44 и 2,9 раз соответственно.При оценке спонтанной двигательной активности ГТС-201 при однократном и субхроническом введении не вызывал изменений локомоторной активности, что позволяет исключить психостимулирующее действие.Полученные данные свидетельствуют о выявлении анксиолитической активности в фармакологическом профиле низкомолекулярного миметика2-й петли BDNF.Литература

Изучены анксиолитические свойства димерных дипептидных миметиков 1-й (ГСБ-214), 2-й (ГТС-201) и 4-й (ГСБ-106) петель мозгового нейротрофического фактора (BDNF), взаимодействующих с TrkB-рецепторами и по-разному активирующих пострецепторные сигнальные пути. Впервые в тесте «Приподнятый крестообразный лабиринт» выявлены анксиолитические свойства соединений ГСБ-106 и ГТС-201 в диапазоне доз 0,1 – 5 мг/кг (внутрибрюшинно) при однократном введении и показана зависимость эффекта от дозы у мышей-самцов CD-1. Активация МАРК/ERK1/2 и PI3K/AKT путей определяет наиболее выраженный анксиолитический эффект ГСБ-106 в дозе 1 мг/кг, по сравнению с умеренным действием ГТС-201, преимущественно активирующим МАРК/ERK1/2 путь и отсутствием эффекта у ГСБ-214, влияющего на PI3K/AKT путь. Таким образом, проявление анксиолитической активности миметиков BDNF связано с активацией ERK1/2 и AKT сигнальных путей.

This review is devoted to updating the existing knowledge about pharmacology of the drugs from the group of direct oral anticoagulants (DOACs). Special attention is paid to comparison of the anticoagulant properties of DOACs with traditional (indirect) anticoagulants at various dosage regimens and to study drug interactions of DOACs with drugs from different pharmacological groups. Widely analyzed the side effects associated with errors in the application of DOACs and provided recommendations for their correction, including the using of reversal agents therapy. Based on this, the presented article will be useful to clinicians to familiarize themselves with modern medical strategies based on the use of drugs from the DOACs group for the prevention and treatment of diseases associated with increased blood clotting ability and using of DOACs specific antagonists for treatment overdose of DOACs.