УДК  615.371:577.215.3
DOI: https://doi.org/10.52540/2074-9457.2025.2.77
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Н. С. Голяк, В. М. Царенков, О. А. Сушинская, О. Г. Сечко, С. С. Мальчëнкова

ДОСТИЖЕНИЯ В ОБЛАСТИ РАЗРАБОТКИ ВАКЦИН НА ОСНОВЕ мРНК

Белорусский государственный медицинский университет, г. Минск, Республика Беларусь

В статье описывается структура естественной эукариотической и синтетической мРНК, влияние модификации составных частей синтетической мРНК на иммуногенность, повышение стабильности и эффективности трансляции. Представлены ключевые открытия и достижения, способствующие появлению мРНК-вакцин как лекарственных препаратов. Описаны этапы производства мРНК вакцин, а также структура липидных наночастиц, как единственно одобренная для клинического использования система доставки мРНК. Представлена краткая характеристика двух первых одобренных мРНК вакцин для профилактики Covid-19: Comirnaty^® и Spikevax^®. Показано, что обе вакцины имеют оптимизированную структуру мРНК и кодируют S-белок mut, содержащий две мутации K986P и V987P (P2 S, которые гарантируют, что S-белок остается в антигенно оптимальной конформации до слияния. Обе вакцины доставляются в клетки с помощью липидных наночастиц, состоящих из 50% в молярном соотношении ионизированных липидов, 38,5% холестерина, 10% дистеарилфосфотидилхолина и 1,5% пэгилированного липида. Производители используют разные ионизированные и пегилированные липиды. Обе вакцины представляют собой стерильную белую дисперсию, но состав вспомогательных веществ отличается. Одобренные мРНК-вакцины требуют хранения при низких (-20 °C) Spikevax^® или сверхнизких температурах (-70 °C) Comirnaty^®. В качестве криопротектора используется сахароза. Описаны данные по безопасности применения зарегистрированных вакцин для профилактики Covid-19. Основными нежелательными реакциями являются спайкопатия, неврологические нарушения, возникновение аутоимммунных заболеваний. Показаны перспективы повышения стабильности мРНК вакцин за счет лиофилизации и получения кольцевых мРНК.

Ключевые слова: мРНК, вакцины, структура мРНК, липидные наночастицы (ЛНЧ), катионные липиды, ионизированные липиды, пегилированные липиды, лиофилизированные мРНК-вакцины, самоамплифицирующиеся мРНК-вакцины, кольцевые мРНК-вакцины, безопасность, эффективность.

SUMMARY

S. Golyak, V. M. Tsarenkov, O. A. Sushinskaya, O. G. Sechko, S. S. Malchenkova

ADVANCES IN THE DEVELOPMENT OF MRNA-VACCINES

The article describes the structure of natural eukaryotic and synthetic mRNA, the effect of modification of the components of synthetic mRNA on immunogenicity, increasing stability and translation efficiency. Key discoveries and achievements that contribute to the emergence of mRNA vaccines as drugs are presented. The stages of mRNA vaccine production are described, as well as the structure of lipid nanoparticles as the only mRNA delivery system approved for clinical use. A brief description of the first two approved mRNA vaccines for the prevention of Covid-19: Comirnaty^® and Spikevax^® is presented. Both vaccines have been shown to have an optimized mRNA structure and encode the S protein mut containing two mutations, K986P and V987P (P2 S, which ensure that the S protein remains in an antigenically optimal conformation prior to fusion. Both vaccines are delivered to cells using lipid nanoparticles composed of 50% molar ionized lipids, 38.5% cholesterol, 10% distearylphosphatidylcholine and 1.5% pegylated lipid. The ionized and pegylated lipids used by the manufacturers differ. Both vaccines are a sterile white dispersion, but the excipient composition differs. The approved mRNA-vaccines require storage at low (-20 °C) Spikevax^® or ultra-low temperatures (-70 °C) Comirnaty^®. Sucrose is used as a cryoprotectant. The safety data for the use of registered vaccines for the prevention of Covid-19 are described. The main adverse reactions are adhesion disease, neurological disorders, and the occurrence of autoimmune diseases. The prospects for increasing the stability of mRNA vaccines through lyophilization and obtaining circular mRNA are shown.

Keywords: mRNA, vaccines, mRNA structure, lipid nanoparticles (LNPs), cation lipids, ionized lipids, pegylated lipids, lyophilized mRNA vaccines, self-amplifying mRNA-vaccines, safety, efficacy

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Адрес для корреспонденции:

220116, Республика Беларусь,

г. Минск, пр-т Дзержинского, 83, корп. 15,

УО «Белорусский государственный

медицинский университет»,

кафедра фармацевтической технологии

с курсом повышения квалификации

и переподготовки,

тел. раб.: +375 17 279-42-54,

e-mail: goliakns@mail.ru,

Голяк Н. С.

Поступила 10.06.2025 г.

УДК 615.015.1: 599.323.45
DOI: https://doi.org/10.52540/2074-9457.2025.2.54
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Е. В. Кравченко¹, О. Н. Саванец¹, Д. И. Макеева^2,1, Д. В. Сикита¹, К. В. Бородина¹, О. В. Грибовская¹, Р. Д. Зильберман¹, Н. А. Бизунок²

Действие тетрапептида, структурно родственного С-концевому фрагменту аргинин-вазопрессина, на модели обсессивно-компульсивного расстройства

¹ГНУ «Институт биоорганической химии НАН Беларуси», г. Минск, Республика Беларусь

²УО «Белорусский государственный медицинский университет», г. Минск, Республика Беларусь

Изучено корректорное влияние тетрапептида N-Ac-Trp-Pro-Arg-Gly-NH₂ на ориентировочно-исследовательскую активность мышей, нарушенную квинпиролом (животная модель обсессивно-компульсивного расстройства – ОКР).

Эксперименты проведены на аутбредных мышах ICR (n = 120). Особям группы I назначали две инъекции растворителя (Р; вода очищенная – интраназально (и/н) и внутрибрюшинно (в/б)); группы II – Р (и/н) и квинпирол (КВ) (0,5 мг/кг, в/б); группы III –
В-5 (N-Ac-Trp-Pro-Arg-Gly-NH₂) в дозе 1,0 мкг/кг, и/н и КВ (0,5 мг/кг, в/б); IV – В-5 (1,0 мкг/кг, и/н) и Р (в/б). Проводили групповую актометрию продолжительностью 70 мин с использованием актометра «Ugo Basile», Италия. Выявлено снижение вертикальной двигательной активности (ВДА) в группе мышей, которым вводили КВ (группа II) в сравнении с контролем (в 5 и 6 мин эксперимента, р < 0,05), а также с уровнем ВДА мышей, которым применяли В-5 (в 1 мин – р < 0,05). Введение В-5 накануне назначения КВ препятствовало патологической гипоактивности в период наиболее выраженного стресса «новизны». В последний 5-минутный интервал ВДА грызунов, получавших КВ, статистически значимо возрастала относительно среднего уровня ВДА за 70 мин; В-5 препятствовал соответствующим КВ-индуцированным нарушениям. Эффективность В-5 позволяет рассматривать его как перспективное фармакологическое вещество для терапии расстройств настроения.

Ключевые слова: мыши, актометрия, N-Ac-Trp-Pro-Arg-Gly-NH₂, квинпирол.

SUMMARY 

V. Kravchenko, O. N. Savanets, D. I. Makeeva, D. I. Sikita, K. V. Borodina, О. V. Gribovskaya, R. D. Zilberman, N. A. Bizunok

TETRAPEPTIDE EFFECT STRUCTURALLY RELATED TO THE C-TERMINAL FRAGMENTOF ARGININE VASOPRESSIN ON A MODEL OF OBSESSIVE-COMPULSIVE DISORDER

The corrective effect of tetrapeptide N-Ac-Trp-Pro-Arg-Gly-NH₂ on exploratory and orienting behaviour of mice disrupted by quinpirole (an animal model of obsessive-compulsive disorder - OCD) was studied.

The experiments were conducted on outbred ICR mice (n = 120). Specimen of group I were prescribed  two injections of solvent (S; distilled water – intranasally (i.n.) and intraperitoneally (i.p.)); group II – S (i.n.) and quinpirole (0.5 mg / kg, i.p.); group III – B-5 (N-Ac-Trp-Pro-Arg-Gly-NH₂) at a dose of 1.0 mcg / kg, i.n. and Q (0.5 mg / kg, i.p.); IV–V-5 (1.0 mcg / kg, i.n.) and S (i.p.). Group actimetry was performed for the session lasting for 70 minutes using an actimeter "Ugo Basile", Italy. A decrease in the vertical locomotor activity (VLA) was detected in the group of mice treated with Q (group II) compared with the control (in the 5^th and 6^th minutes of the experiment, p < 0.05), and also with the level of VLA in the mice treated with V–5 (in the 1^st minute, p < 0.05). Injection of V-5 before administering Q prevented pathological hypoactivity during the period of the most pronounced stress of "novelty". In the last 5-minute interval the VLA level of rodents treated with Q increased statistically significantly related to the average VLA level over 70 minutes; V-5 prevented corresponding Q-induced disorders.  The effectiveness of V-5 allows us to consider it as a promising pharmacological substance for the treatment of mood disorders.

Keywords: mice, actimetry, N-Ac-Trp-Pro-Arg-Gly-NH₂, quinpirole.

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Адрес для корреспонденции:

220141, Республика Беларусь,

г. Минск, ул. Академика Купревича, 5/2,

лаборатория токсикологии

Института биоорганической химии

НАН Беларуси

тел. раб. 8017-234-04-80,

e-mail: kravchenko@iboch.by,

Кравченко Е. В.

Поступила 10.06.2025 г.

УДК 612.392.69:616-084
DOI: https://doi.org/10.52540/2074-9457.2025.2.65
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М. Р. Конорев, Н. Р. Прокошина, Т. М. Соболенко

ЦИНК: ОТ ПРОФИЛАКТИКИ ДЕФИЦИТА ДО ТЕРАПЕВТИЧЕСКОГО ПОТЕНЦИАЛА. ЧАСТЬ 2

Витебский государственный ордена Дружбы народов медицинский университет, г. Витебск, Республика Беларусь

Дефицит цинка, широко распространенный во всем мире, оказывает неблагоприятное воздействие на здоровье человека. Недостаток данного микроэлемента может отягощать течение различных заболеваний, сопровождающихся окислительным стрессом и процессом воспаления. Учитывая разнообразные функции цинка в организме, в последние годы возрос интерес исследователей к изучению его терапевтического потенциала. Во второй части обзора проанализированы результаты мета-анализов, систематических обзоров и клинических исследований за последние 10 лет по изучению возможности применения препаратов цинка при ряде патологических состояний. Представлены исследования по оценке положительного влияния добавок цинка на репродуктивное здоровье мужчин и женщин, снижение риска младенческой смертности, параметры роста и развития детей. Учитывая неблагоприятные последствия дефицита цинка в период беременности, обсуждается целесообразность использования добавок цинка у женщин с низким его потреблением. Показаны потенциальные возможности применения препаратов цинка в терапии респираторных вирусных инфекций, включая Covid-19, сердечно-сосудистых заболеваний, сахарного диабета, ожирения, заболеваний кожи. Рассмотрены перспективы биообогащения цинком продуктов питания для коррекции нарушений кишечной микробиоты.

Ключевые слова: цинк, дефицит цинка, репродуктивное здоровье, здоровье детей, инфекции верхних дыхательных путей, Covid-19, сердечно-сосудистые заболевания, сахарный диабет, ожирение, заболевания кожи, микробиота.

SUMMARY

R. Konorev, N. R. Prakoshyna, T. M. Sabalenka

ZINC: FROM DEFICIENCY PREVENTION TO THERAPEUTIC POTENTIAL. PART 2

Zinc deficiency widespread throughout the world has an adverse effect on human health. Lack of this microelement can aggravate the course of various diseases accompanied by oxidative stress and inflammation. Given the diverse functions of zinc in the body, in recent years, researchers have shown increasing interest in studying its therapeutic potential. The second part of the review analyzes the results of meta-analyses, systematic reviews and clinical studies over the past 10 years on the possibility of using zinc preparations in a number of pathological conditions. Studies are presented to assess the positive effect of zinc supplements on the reproductive health of men and women reducing the risk of infant mortality, and growth and development parameters in children. Given the adverse effects of zinc deficiency during pregnancy, the advisability of using zinc supplements in women with low zinc intake is discussed. The potential uses of zinc preparations in the treatment of the respiratory viral infections, including Covid-19, cardiovascular diseases, diabetes, obesity, and skin diseases are shown. The prospects of biofortification of food products with zinc to correct intestinal microbiota disorders are considered.

Keywords: zinc, zinc deficiency, reproductive health, children's health, upper respiratory tract infections, Covid-19, cardiovascular diseases, diabetes mellitus, obesity, skin diseases, microbiota.

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Адрес для корреспонденции:

210009, Республика Беларусь,

г. Витебск, пр. Фрунзе, 27,

УО «Витебский государственный ордена

Дружбы народов медицинский университет»,

кафедра общей и клинической фармакологии

с курсом ФПК и ПК,

тел. раб.: 8 (0212) 58 13 87,

Конорев М. Р.

Поступила 06.06.2025 г.

УДК 631.4:544.623
DOI: https://doi.org/10.52540/2074-9457.2025.2.41
Скачать статью 

Г. Н. Бузук 

МЕТОД ИЗМЕНЯЮЩЕГОСЯ ГЕОМЕТРИЧЕСКОГО КОЭФФИЦИЕНТА ДЛЯ ОПРЕДЕЛЕНИЯ ЭЛЕКТРОПРОВОДНОСТИ/ЭЛЕКТРОСОПРОТИВЛЕНИЯ ПОЧВ

г. Витебск, Республика Беларусь

Представлен новый метод калибровки и обработки данных по электросопротивлению почв, полученных с использованием квадратной установки и неизолированных электродов. Метод основан на впервые выявленной линейной зависимости между глубиной погружения электродов в калибровочный раствор 0,001 М калия хлорида и геометрическим коэффициентом установки. Аппроксимация зависимости с помощью линейной регрессии позволяет оперативно рассчитывать актуальные значения геометрического коэффициента для различных субстратов, включая почву и водные экстракты. Разработано устройство для контролируемого заглубления электродов, обеспечивающее воспроизводимость измерений и снижение экспериментальных погрешностей. Предложенный подход открывает новые перспективы для стандартизации методики в почвенных и агрохимических исследованиях.

Такие измерения электросопротивления могут служить индикатором специфических условий местообитаний, способствующих формированию уникальных фитохимических профилей и адаптивных стратегий лекарственных растений.

Ключевые слова: электросопротивление почвы, геометрический коэффициент, квадратная установка, неизолированные электроды, линейная регрессия, калибровочный раствор 0,001 М калия хлорида, контролируемое заглубление, почвенный экстракт, методика измерений.

SUMMARY

N. Buzuk

METHOD OF VARIABLE GEOMETRY FACTOR IN SOIL ELECTRICAL CONDUCTIVITY/RESISTIVITY DETERMINATION

A novel method for calibrating and processing soil electrical resistivity data has been developed using a square electrode configuration with non-insulated (bare) electrodes. The method is based on a newly identified linear relationship between electrode immersion depth in a 0.001 M potassium chloride (KCl) calibration solution and the geometric factor of the configuration. This dependence approximation using linear regression allows to calculate topical data of the geometric factor for various substrates including soils and aqueous extracts. A device for controlled electrode immersion providing measurements reproducibility and reduction of experimental errors has been designed. The proposed approach opens up new prospects for standardizing the methodology in soil and agrochemical research.

Such measurements of electrical resistivity can serve as an indicator of specific habitat conditions contributing to the formation of unique phytochemical profiles and adaptive strategies of medicinal plants.

Keywords: soil electrical resistivity, geometric factor, square electrode configuration, bare electrodes, linear regression, calibration solution, potassium chloride (KCl), controlled immersion, soil extract, measurement methodology.

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Бузук, Г. Н. Определение трофности почв электрофизическим методом. Сообще-ние 2. Конструкция электродов и способ расчета геометрического коэффициента / Г. Н. Бузук // Вестник фармации. – 2021. – № 4. –
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Бузук, Г. Н. Определение трофности почв электрофизическим методом. Сообщение 3. Корректировка влияния влажности / Г. Н. Бузук // Вестник фармации. – 2021. – № 4. – С. 74–84. – DOI: 10.52540/2074-9457.2021.4.74.

Бузук, Г. Н. Определение трофности почв электрофизическим методом. Сообще-ние 4. Почвенная матрица / Г. Н. Бузук // Вестник фармации. – 2022. – № 1. – С. 56–62. – DOI: 10.52540/2074-9457.2022.1.56.

Бузук, Г. Н. Определение трофности почв электрофизическим методом. Сообще-ние 5. Полевые испытания / Г. Н. Бузук // Вестник фармации. – 2022. – № 2. – С. 65–76. – DOI: 10.52540/2074-9457.2022.2.65.

Бузук, Г. Н. Определение трофности почв электрофизическим методом. Сообще-ние 6. Квадратная установка, конструкция электродов и способ расчета геометрического коэффициента / Г. Н. Бузук // Вестник фармации. – 2022. – № 3. – С. 23–29. – DOI: 10.52540/2074-9457.2022.3.23.

Бузук, Г. Н. Определение трофности почв электрофизическим методом. Сообщение 7. Новое в технике измерений и расчетов / Г. Н. Бузук // Вестник фармации. – 2024. – № 2. – С. 31–41. – DOI: 10.52540/2074-9457.2024.2.31.

Бузук, Г. Н. Определение трофности почв электрофизическим методом. Сообщение 8. Полевые испытания с квадратной установкой / Г. Н. Бузук // Вестник фармации. – 2024. – № 4. – С. 44–54. – DOI: 10.52540/2074-9457.2024.4.44.

Бузук, Г. Н. Определение трофности почв электрофизическим методом. Сообщение 9. От линеаризации к экспоненциальной регрессии и корректировке влажности / Г. Н. Бузук // Вестник фармации. – 2025. – № 1. – С. 58–69. – DOI: 10.52540/2074-9457.2025.1.58.

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Effects of equilibrium time on electrical conductivity measurements using soil-water extracts and soil saturated paste / B. S. Seo, K. S. Lee, Y. J. Leong, W. J. Choi // Korean journal of soil science and fertilizer. – 2021. – Vol. 54, N 2. – P. 257–263. – DOI: 10.7745/KJSSF.2021.54.2.257.

Aboukila, E. Assessment of saturated soil paste salinity from 1:2.5 and 1:5 soil-water extracts for coarse textured soils / E. Aboukila, E. F. Abdelaty // Alexandria Science Exchange journal. – 2017. – Vol. 38, N 4. – P. 722–732. – DOI: 10.21608/ASEJAIQJSAE.2017.4181.

Aboukila, E. F. Estimation of saturated soil paste salinity from soil-water extracts / E. F. Aboukila, J. B. Norton // Soil science. – 2017. – Vol. 182, N 3. – P. 107–113. – DOI: 10.1097/SS.0000000000000197.

Evaluation of 1:5 soil to water extract electrical conductivity methods / Y. He, T. DeSutter, L. Prunty [et al.] // Geoderma. – 2012. – Vol. 185. – P. 12–17. – DOI: 10.1016/j.geoderma.2012.03.022.

Kargas, G. Comparison of soil EC values from methods based on 1:1 and 1:5 soils to water ratios and ECe from saturated paste extract-based method / G. Kargas, P. Londra, A. Sgoubopoulou // Water. – 2020. – Vol. 12, N 4. – P. 1–12. – DOI: 10.3390/w12041010.

Kargas, G. The effect of soil texture on the conversion factor of 1:5 soil/water extract electrical conductivity (EC 1:5) to soil saturated paste extract electrical conductivity (ECe) / G. Kargas, P. Londra, K. Sotirakoglou // Water. – 2022. – Vol. 14, N 4. – P. 1–10. – DOI: 10.3390/w14040642.

An Investigation of the relationship between the electrical conductivity of the soil saturated paste extract ECe with the respective values of the mass soil/water ratios 1:1 and 1:5 (EC1:1 and EC1:5) / G. Kargas, I. Chatzigiakoumis,
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Evaluation and analysis of different regression models for estimation of ECe from EC1:5–With a case study from Buin-Zahra, Iran / M. Hassannia, B. Nazari, A. Kavani, A. Sotoodehnia // Irrigation and drainage. – 2020. – Vol. 69, N 5. – P. 1192–1203. – DOI: 10.1002/ird.2488.

Modeling the electrical conductivity relationship between saturated paste extract and 1:2.5 dilution in different soil textural classes / M. M. Omar, M. Shitindi, B. H. J. Massawe [et al.] // Frontiers in soil science. – 2024. – Vol. 4. – P. 1–10. – DOI: 10.3389/fsoil.2024.1421661.

Spiteri, K. Estimating the electrical conductivity of a saturated soil paste extract (ECe) from 1:1 (EC1:1), 1:2 (EC1:2) and 1:5 (EC1:5) soil: water suspension ratios, in calcareous soils from the Mediterranean Islands of Malta / K. Spiteri,
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Correlation between electrical conductivity in saturated paste extracts and different diluted extracts (1/2.5, 1/5) of coarse-textured soils / D. Bakhti, M. Oustani, M. T. Halilat [et al.] // Journal of agriculture and applied biology. – 2024. – Vol. 5, N 1. – P. 18–34. – DOI: 10.11594/jaab.05.01.02.

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Поступила 06.06.2025 г.