A three-component reaction of 3,5-diacetyl-2,6-dimethylpyridine, p-N-dimethylaminobenzaldehyde and phenylhydrazine in the presence of KOH in ethanol gave the condensation product of two p-N-dimethylaminobenzaldehyde and phenylhydrazine molecules, namely bis(biarylhydrazone). Structure of the obtained derivative was proved by the 1H and 13C NMR spectroscopy and X-ray diffraction analysis data. It was shown that the bis(biarylhydrazone) derivative has high antiradical and cytoprotective activity.

Introduction. A human metagenome is 100 times larger than its own genome and determines many physiological processes in our body. The metagenome has specific characteristics for each population, which determines the markers of diseases, the course and ways of preventing and treating pathologies. Materials and methods. The studies were carried out according to the procedures of IHMC (International Human Microbiome Consortium) standards. Results. These studies of human metagenome are the first among the Central Asian population. Comparison of Kazakh samples of the gut microbiome with samples of other populations demonstrated the main differences and similarities and found that the microbiome depends on nutrition, climatic and geographical features, lifestyle, social factors and age. We compared the distal gut microbiota of 149 Kazakhstan individuals aged 25 - 65 years. Our studies have shown that microbiomes are different depending on climatic and geographical features, lifestyle, social factors and age. mOTU analysis showed that a microbiome core of our population form by the genera Faecalibacterium, Bacteroides, Dorea, Collinsella, Oscillibacter, Ruminococcus, Subdoligranulum, Coprococcus, Escherichia, Eberichia, Eberichia Roseburia, Parabacteroides and Prevotella. The microbiome core does not change throughout life, and their ratio determines the human enterotype, that determine the risks of developing microbiome-associated diseases, especially the metabolism of drug substances and dietary features to maintain health. The Kazakh samples mostly belong to Enterotype 3. As well as at the mOTU level we found significant (Spearman FDR 0.05) associations to many categories of nutrients, which were studied using FFQ questionnaire. Due to study, the functionality of bacterial genes using the KEGG database were defined the 44 KEGG pathways with significant differences depending on clinical and laboratory characteristics, as well as an anamnesis. Conclusion The main characteristics of the gut metagenome of Kazakhstan individuals were determined. Крспе Адамны метагеномы зн геномынан 100 есе лкен жне денемздег кптеген физиологиялы процестерд анытайды. Метагеноманы р популяцияа тн сипаттамалары бар, олар ауруларды белглерн, патологияны алдын-алу жне емдеу жолдарын анытайды. Материалдар мен дстер. Зерттеулер IHMC (Халыаралы адам микробиомасы консорциумы) стандарттарына сйкес жргзлд. Нтижелер. Бл зерттеулер Орта Азияда популяция микробиомын зерттеу бойынша дниежзндег алашы зерттеу. шек микробиомыны азастанды лглерн баса популяциялармен салыстыру негзг айырмашылытар мен састытарды крсетт жне микробиомны таматануа, климатты жне географиялы ерекшелктерне, мр салтына, леуметтк факторлара, жасына байланысты екендг аныталды. Бз 25 пен 65 жас аралыындаы 149 азастандыты дистальды шект микробиоталарын салыстырды. Бзд зерттеулермз микробиомаларды климатты жне географиялы ерекшелктерге, мр салтына, леуметтк факторлара, жасына байланысты ерекшеленетнн крсетт. мOTU дегейндег талдау микробиомны ядросын анытауа ммкндк берд, оны рамына келес туыстар кред: Faecalibacterium, Bacteroides, Dorea, Collinsella, Oscillibacter, Ruminococcus, Subdoligranulum, Coprococcus, Escherichia, Eberichia, Eberichia Roseburia, Parabacteroides жне Prevotella Микробиомны ядросы мр бойы згермейд жне денсаулыты сатау шн ауруларды даму аупн анытайтын, дрлерд метаболизм мен таматану ерекшелктерн анытайтын адамны энтеротипн райды. азастанды лглер негзнен энтеротип 3-ке енед. Сонымен атар, MOTU дегейнде FFQ сауалнамасы арылы зерттелген кптеген оректк заттарды санаттары бар маызды ауымдастытар табылды (Spearman FDR 0.05). KEGG деректер базасын олдана отырып, бактериалды гендерд функционалдыын зерттеуге сай клиникалы жне зертханалы сипаттамаларына, сондай-а медициналы тарихына байланысты 44 KEGG жолы айтарлытай айырмашылытары бар екендг аныталды. орытынды. азастандытарды шек метагеномыны негзг сипаттамалары аныталды. Введение. Метагеном человека в 100 раз превышает собственный геном и определяет многие физиологические процессы в нашем организме. Метагеном имеет специфические характеристики для каждой популяции, что определяет маркеры заболеваний, течение и пути профилактики и лечения патологий. Материалы и методы. Исследования проведены согласно процедурам стандартам IHMC (International Human Microbiome Consortium). Настоящее исследование является первым в мире по изучению микробиома популяции Центральной Азии. Сопоставление казахских образцов кишечного микробиома с образцами других популяций, продемонстрировали основные отличия и сходства и установили что микробиом зависит от питания, климато-географических особенностей, образа жизни, социальных факторов, возраста. Мы сравнили микробиоту дистальной части кишечника 149 казахстанцев в возрасте от 25 до 65 лет. Результаты. Наши исследования показали, что микробиомы различаются в зависимости от климатических и географических особенностей, образа жизни, социальных факторов, возраста. Анализ на уровне mOTU позволил определить микробиомное ядро, которое ввключает следующие роды Faecalibacterium, Bacteroides, Dorea, Collinsella, Oscillibacter, Ruminococcus, Subdoligranulum, Coprococcus, Escherichia, Eberichia, Eberichia Roseburia, Parabacteroides и Prevotella. Микробиомное ядро не изменяется в течение жизни, и формирует энтеротип человека, который определяет риски развития заболеваний, метаболизм лекарственных веществ и особенности питания для поддержания здоровья. Казахстанские образцы в основном относятся к энтеротипу 3. Кроме того, на уровне mOTU мы обнаружили значимые (Spearman FDR 0,05) ассоциации со многими категориями питательных веществ, которые были изучены с помощью опросника FFQ. В связи с изучением функциональности бактериальных генов с использованием базы данных KEGG были определены 44 пути KEGG со значительными различиями, в зависимости от клинических и лабораторных характеристик, а также от анамнеза. Заключение. Определены основные характеристики кишечного метагенома казахстанцев.

It has been thought that caloric restriction favors longevity and healthy aging where autophagy plays a vital role. However, autophagy decreases during aging and that can lead to the development of aging-associated diseases such as cancer, diabetes, neurodegeneration, etc. It was shown that autophagy can be induced by mechanical or chemical stress. In this regard, various pharmacological compounds were proposed, including natural polyphenols. Apart from the ability to induce autophagy, polyphenols, such as resveratrol, are capable of modulating the expression of pro- and anti-apoptotic factors, neutralizing free radical species, affecting mitochondrial functions, chelating redox-active transition metal ions, and preventing protein aggregation. Moreover, polyphenols have advantages compared to chemical inducers of autophagy due to their intrinsic natural bio-compatibility and safety. In this context, polyphenols can be considered as a potential therapeutic tool for healthy aging either as a part of a diet or as separate compounds (supplements). This review discusses the epigenetic aspect and the underlying molecular mechanism of polyphenols as an anti-aging remedy. In addition, the recent advances of studies on NAD-dependent deacetylase sirtuin-1 (SIRT1) regulation of autophagy, the role of senescence-associated secretory phenotype (SASP) in cells senescence and their regulation by polyphenols have been highlighted as well. Apart from that, the review also revised the latest information on how polyphenols can help to improve mitochondrial function and modulate apoptosis (programmed cell death).

The purpose of this study was to study the potential therapeutic properties of water-alcohol extracts of bilberry, blueberries, cowberries, cranberries, on the model of experimental streptozotocin diabetes mellitus. Research material and methods. Wild bilberry, cowberries, cranberries and blueberries collected in the summer and autumn of 2018 in the Surgut district of the Khanty-Mansiysk district of the Tyumen region of the Russian Federation were used to obtain polyphenolic water-alcohol extracts of Northern berries. The extracts were concentrated in a vacuum evaporator to the level of polyphenols in 10 mg / ml. the Rats were injected with polyphenol extracts at the rate of 10 mg / kg (the input volume of 0.2-0.3 ml). Results. The concentration of polyphenols in the samples was studied using a commercial set for determining the concentration of polyphenols «Polyphenols folin-ciocalteu (ENOLOGY line by BioSytems. Spain)», in accordance with the instructions of the reagent manufacturer. The results were expressed in the equivalent of Gallic acid, i.e. mg of Gallic acid/ml of berry extract (mgGAE /ml Conclusion. A model of type II diabetes mellitus obtained in rats with streptozotocin was used to study the effect of extracts of wild bilberry, cowberries, cranberries and blueberries in North-Western Siberia on the level of glycemia and insulin resistance, lipid metabolism, the level of expression of CRP, IL-6 and TNF-α in the liver and adipose tissue of rats, and histopathological changes in pancreatic tissue were also established. Determined that extracts of bilberry, cowberries, cranberries and blueberry on the model of diabetes reduces the severity of insulin resistance such as Metformin, lower blood glucose levels (except lingonberry extract), reduce the concentration of triglycerides (except cowberries extract), reduces the concentration of LDL (except cranberries and cowberries). The use of blueberry extract on the background of diabetes reduces the expression of inflammatory cytokine genes IL-6, TNF-α and CRP. At the same time, extracts of Northern berries in the blood plasma prevent excessive release of free radicals and increase antioxidant activity. Pathomorphological studies of pancreatic tissue document a lower degree of damage to the Langerhans islets against the background of the introduction of Northern berry extracts.

New antidiabetic agents are being sought because of the global problem with diabetes. Amidoxime derivatives are known to have antidiabetic activity. β-Aminopropionamidoxime bases and pharmacologically acceptable salts of O -aroyl-β-(morpholin-1-yl)propionamidoximes and 5-substituted phenyl-3-β-(piperidin-1-yl and morpholin-1-yl)ethyl-1,2,4-oxadiazoles were screened in vitro for antidiabetic activity manifested as inhibition of α-amylase and α-glucosidase. Compounds with pronounced antidiabetic properties were identified. The series of 3,5-disubstituted 1,2,4-oxadiazoles were more active than the series of O -aroyl-β-aminopropionamidoximes. The results could be used for further in vivo screening of the antidiabetic properties of the most promising compounds with a preliminary assessment of their mean toxic doses in animals.

It is fundamental truth that breast milk is the best food for a newborn, providing it with energy, high-quality nutrients, as well as a large variety of biologically active components necessary for adequate physical and psychomotor development. Acting either as part of complex biological structures or separately, the breast milk components, including personalized microbial and immune, regulate morphogenesis at the molecular and cellular level, determine the metabolism nature, guide the development of mucosal immunity in the child’s body. It is impossible to identify any component of breast milk as the main component that determines its functional activity and provides the benefits of natural feeding. The purpose of this review is to describe the role of prebiotics in breast milk and infant formula for the formation and maintenance of a healthy baby intestinal microbiota, which is a key element in the formation of normal digestion, a functionally sound immune system and metabolism.

O-Tosylates-β-aminopropioamidoximes and chlorides of 2-amino-4,5-dihydrospyropyrazolylammoniums have been studied in vitro for anti-tuberculosis and anti-diabetic activity. In two groups of compounds containing β-amino groups: piperidin-1-yl, morpholin-1-yl, thiomorpholin-1-yl, 4-phenylpiperazine-1-yl, benzimidazol-1-yl (with the exception of the benzimidazole derivative in the spiro derivative series), drugs with an average anti-tuberculosis activity were detected on the DS strains of M. tuberculosis (MBC 50 μg/ml) and with moderate anti-diabetic α-amylase activity (27% to 29%) in the first row, containing β-amino groups: piperidin-1-yl, morpholin-1-yl and in the second row – piperidin-1-yl. References [1] Singh A., Prasad R., Balasubramanian V., Gupta N., Gupta P. Prevalence of adverse drug reaction with first-line drugs among patients treated for pulmonary tuberculosis // Clinical epidemiology and global health. 2015. Vol. 3. P. 80-90. [2] Yang T.W., Park H.O., Jang H.N., Yang J.H., Kim S.H., Moon S.H., Byun J.H., Lee C.E., Kim J.W., Kang D.H. Side effects associated with the treatment of multidrug-resistant tuberculosis at a tuberculosis referral hospital in South Korea: A retrospective study // Medicine. 2017. Vol. 96, Issue 28. e7482. [3] Forouhi N.G. and Wareham N.J. Epidemiology of diabetes // Medicine (Abingdon). 2014. Vol. 42, N 12. Р. 698-702. [4] Williams textbook of endocrinology (12th ed.). Philadelphia: Elsevier/Saunders. P. 13711435. ISBN 978-1-4377-0324-5. [5] Australian Indigenous HealthInfoNet, Chronic conditions: Diabetes. Accessed 31 August 2016. [6] Zaklyuchitel'nyy otchet po proektu KN MON RK «Proizvodnye β-aminopropioamidoksimov kak novye, netoksichnye i aktivnye tuberkulostatiki», 2003 g. Inv. nomer № 0203 RK 00809. P. 57-62. [7] Patent RK № 32421. Primenenie gidrohlorida O-para-toluoil-β-(morfolin-1-il)propioamidoksima v kachestve protivodiabeticheskogo sredstva / Kayukova L.A., Praliev K.D., Dyusembaeva G.T., Gulyaev A.E., Shul'gau Z.T., Sergazy Sh.D., Nurgozhin T.S.; opubl. 16.10.2017, Byul. №10. [8] Baytursynova G.P., Kayukova L.A., Geronikaki A., Praliev K.D., Kenesbekova A.K. Cintez O-para-toluolsul'fonil-β-aminopropioamidoksimov // Himicheskiy zhurnal Kazahstana. 2016. N 4. P. 114-122. [9] Kayukova L.A., Baytursynova G.P., Geronikaki A., Praliev K.D., Akatan K., Shaymor- dan E., Kaynarbaeva Zh.N. Tozilaty β-aminopropioamidoksimov v usloviyah otschepleniya uhodyaschey gruppy // Himicheskiy zhurnal Kazahstana. 2016. N 4. P. 328-335. [10] Mashkovskiy D.M. Lekarstvennye sredstv. 14-e izdanie. M.: Novaya volna, 2002. Vol. 2. P. 273-288. [11] Doulou I., Kontogiorgis C., Koumbis A.E., Evgenidou E., Hadjipavlou-Litina D., Fylaktakidou C. Synthesis of stable aromatic and heteroaromatic sulfonyl-amidoximes and evaluation of their antioxidant and lipid peroxidation activity // European Journal of Medicinal Chemistry. 2014. N 80. P. 145-153. [12] Bernfeld P. // in: Methods in Enzymology, Colowick S. P. and Kaplan N. O. (eds.). NewYork: Academic Press, 1955. P. 149-158.

Histologic research is one of the most reliable methods of diagnosis of pathologies of organs and tissues. This method allows estimating both macroscopic and microscopic structural changes in organs and tissues of animals. Data obtained in the course of the pathomorphological research have fundamental value for studying toxic influence of preparations at the stage of preclinical research. Results of histologic structure of internals and tissues of laboratory Sprague Dawley rats are presented in this article. As a result of experiments it has been established that no side effects have been revealed at preparation administration toanimals. “Microfit” biological preparation exerted no negative impact on functional activity of internals of an organism of rats, caused no allergic reactions. The macroscopic research of internals of all experimental animals revealed no pathology after autopsy. Pathomorphological research of the main organs and tissues confirms safety of the structure of tissues. Following the research results, within one month (30 days) of administration of the biological preparation, it has been established that in case of course intragastric administration of “Microfit” preparation to white Sprague Dawley rats in a conditional-therapeutic dose (30 mg/kg) and a dose exceeding the conditional-therapeutic dose by 10 times (300 mg/kg), the preparation has no toxic effect on condition of internals and tissues.

It is recognized that breast milk is the ideal food for newborns. Indeed breast milk can provide basic guidelines to improve the composition of ingredients in adapted infant formulae. One of the main parts of breast milk is milk fat. Although the exact functionality of the entire spectrum of fat is not yet fully understood, it is known that various lipids present in breast milk, can modulate functions of the gastrointestinal tract, the lipoprotein metabolism, the structure and function of cell membranes, as well as many signal pathways in the infant's organism. In this paper we tried to present evidence that dietary cholesterol (CHOL) is a very important component of the infant's nutrition. Meanwhile, almost all infant formulae, both cow and goat milk based, use nearly only vegetable oils as their fat component providing phytosterols, rather than CHOL as in breast milk. It is known that breast milk is a rich source of CHOL and phytosterols cannot perform the functions of CHOL. One can imagine that when the infant is transferred to artificial feeding with such formulae, and denied the opportunity to receive dietary CHOL in any useful amounts, this may affect outcomes like optimal child development, and may have a major long-term 'programming' effect on the metabolism of CHOL. We propose to discuss the thesis of the great importance of the presence of CHOL in infant formulae. The applied value of this thesis is the need to optimize the fat component of breast milk substitutes by introducing CHOL, for example, in the composition of milk fat. Although it is clear that compelling evidence of the potential benefits of adding various sources of CHOL infant formula is insufficient, at this stage, there is cause for a critical discussion and review of the composition of functional components of breast milk substitutes.

This article describes the results of experiments dealing with application of gel form of recombinant human angiogenin (Farmagen) used in the treatment of regular and suppurative tender wounds.

This review emphasises the genotypical heterogeneity of the population of goats, which at the molecular level is manifested in the form of gene polymorphism in the milk proteins. Polymorphic genes, represented in the population of heterogeneous alleles, cause a wide variance in the chemical composition and processing properties of goat milk. We summarized the literature about the main features of genes encoding proteins of goat milk. It is stressed that goat's milk, due to genetic polymorphism has a great value when creating a new functional food product for children.

This review summarizes the most complete information on such fundamentally important quality parameters of goat milk as the cellular composition of somatic cells and the structure of cytoplasmic debris in milk. It also focuses on the characterization of an essential component of the energetic value and nutritional content of milk--milk fat globules and milk fat globule membranes. The survey also clarifies some of the terms and meanings of physiological processes associated with the formation of the milk of various ruminants and breast milk.

The reaction of 3-amino-4,6-dimethylpyridin-2(1H)-one and 3-amino-4-phenylpyridin-2-one with acyl isothiocyanates (benzoyl-, 4-bromobenzoyl-, and methacryloyl isothiocyanates) and with allyl isothiocyanate has been studied. The N-carbamothioyl methacrylamides and N-allylthioureas obtained undergo intramolecular heterocyclization reactions to give the corresponding 1,3-thiazin-4-one and 1,3-thiazoline derivatives. It was found that the starting 3-amino-4,6-dimethylpyridin-2(1H)-one shows antiradical activity but the synthesized thioureas do not.

Investigations aimed at the development of a combined wound-healing preparation on a hydrophilic ointment base have been carried out. Copolymers of acrylic acid and its derivatives with a new divinyl monomer, β-vinyloxyethylamide of acrylic acid, are proposed as the bases. It is established that these ointment bases exhibit sufficiently high osmotic activity. Polymer-based complexes including the ethereal oil of smooth wormwood and the proteolytic enzyme protosubtilin showed pronounced antibacterial and wound-healing activity.