Background. The combination of metabolic-associated fatty liver disease (МAFLD) with iron overload occurs in approximately 1/3 of patients and is extremely difficult to treat. In addition to the fact that no specific treatments have been developed for this МAFLD form, there are also few experimental models on which such agents could be tested.Objective: to create a MAFLD model and to study the effectiveness of using human placenta hydrolyzate (HPH) in experiment.Material and methods. In experiment, the rats were divided into three groups: Group 1 was on a normal diet and drinking water, in Groups 2 and 3, a model of liver iron overload was reproduced by intraperitoneal administration of iron sulfate for 12 days under conditions of adding saturated fats (palm oil) and fructose to the diet. On Day 13 of the study, blood was collected from animals in Groups 1 and 2 for biochemical testing and autopsy material (liver, kidneys, brain, heart) for histopathological examination. In Group 3, standardized HPH was administered in a therapeutic dose intramuscularly for 4 weeks. On Day 41, blood and autopsy material were collected. The model was used to test the effectiveness of using standardized HPH and to characterize complex changes in more than 20 biomarkers of liver and kidney functions, hematopoiesis, inflammation, and thrombus formation.Results. HPH injections were shown to be an effective treatment for iron overload МAFLD. Specifically, after reproducing the model on Day 41, levels of ferritin (intact: 201±45 μg/l; model: 254±12 μg/l; p<0.0001), aspartate aminotransferase (AST) (intact: 114.9±27.3 U/l; model: 301,3±30,3 U/l; р<0.000001), alanine aminotransferase (ALT) (intact: 22.8±3.2 U/l; model: 58.7±5.5 U/l; p<0.00014), leukocytes (intact: 4.6±1.3×109 cells/l; model: 6.9±0.8×109 cells/l; p<0.01), thrombocytes (intact: 509.7±121.6×109 cells/l; model: 820.2±50.5×109 cells/l; p<0.01) increased reliably. Total protein levels (intact: 46.2±2 4.6 g/l; model: 45.5±5.8 g/l; p=0.002), serum creatinine (intact: 35.7±1.2 μmol/l; model: 23.3±1.4 μmol/l; p<0.00001) and glomerular filtration rate (GFR) (intact: 169±5 ml/min/1.73 m2; model: 154.1±7.1 ml/min/1.73 m2; p=0.04) decreased. HPH administration resulted in normalization of the listed indicators of polyorgan pathology on Day 41: reliable reduction of ferritin (141±24 μg/l; p<0.001), AST (166.7±51.3 U/l; p=0.00±77), ALT (36.4±7.2 U/l; p=0.00001), leukocytes (4.5±2.7×109 cells/l; p=0.039), thrombocytes (639.0±92.3×109 cells/l; p=0.00157) and reliable elevation of total protein (55.9±3.8 g/l; p=0.0014), normalization of creatinine (27.7±1.5 μmol/l; p=0.0002), and GFR (169.8±6.2 ml/min/1.73 m2; p=0.0011). Histological analysis revealed that HPH promoted hepatic iron excretion while preventing renal, brain, and myocardial damage in the proposed iron-overload МAFLD model.Conclusion. The administration of standardized HPH is effective and safe in the therapy of experimental iron overload МAFLD and prevents polyorgan pathology.

Objective: to investigate the antitumor effects of various forms of vitamin B12 in combination with various synergistic vitamins and evaluate the prospects for clinical applications. Material and methods. Cell lines BT-474 (breast ductal carcinoma) and A549 (lung carcinoma) were used as an in vitro cell model, and transplantable epidermoid Lewis lung carcinoma (LLC) was used as an in vivo animal tumor model. Animal studies of LLC were carried out on 25 male F 1 hybrid mice (age 2.5–3 months, body weight 23–26 g). In silico research was conducted as a systematic computer analysis of 9,326 scientific sources. Results. In vitro studies on cultures of two human tumor cell lines (BT-474 and A549) confirmed the cytotoxic effect of vitamin B12 (aquacobalamin). It has been shown that vitamin B12 has weak cytotoxic properties in the concentration range of 3.125–200 μg/L (IC50>200 nM), and its hydrophobic derivative (heptamethyl cyanoquacobyric acid ester) significantly reduces the survival of tumor lines. BT-474 and A549 cells at high concentrations (100–200 µg/l, IC50~100 nM). Experimental animals with an in vivo LLС model easily tolerated a drug based on vitamin B12. Exposure to the drug up to the 21 st day of LLС development was accompanied by an increasing tendency to inhibit tumor growth by 10–20% (р=0.059). The results of a systematic in silico review of the literature show that clinical data confirmed the significant antitumor effect of vitamin B12. Conclusion. The cellular model indicated the antitumor properties of vitamin B12 and its hydrophobic derivative. With subchronic intragastric administration of B12 to tumor-bearing animals, a steady tendency to inhibit the LLС growth was observed. Analysis of clinical data confirmed the feasibility of the antitumor use of vitamin B12 individually and in combination with synergistic vitamins.

It is well known that a complex of nervous and hormonal signals during stress stimulates adrenal glands to secrete adrenaline, norepinephrine and cortisol. Much less attention has been paid to the roles of intermediate signaling proteins mediating the effects of “stress hormones”, neurotransmitters, and other signaling molecules. This paper presents the results of a systematization of studies of glycogen synthase kinases GSK-3α and GSK-3β, whose excessive activity aggravates the course of chronic stress, has a negative effect on neuronal survival and adaptation processes. Lithium ions are a natural inhibitor of the excessive activity of both GSK-3, which partly determines the normothymic and antidepressant effects of lithium drugs. Taking lithium salts based on organic anions is the safest and most effective way to replenish lithium deficiency in the body. The prospects for the use of lithium ascorbate to increase the body's adaptive reserves are considered.

Combined oral contraception and treatment of new coronavirus infection (COVID-19): issues of drug interaction This article examines the interaction of combined oral contraceptives with drugs recommended in the treatment of new coronavirus infection (COVID-19) at the pharmacodynamic and pharmacokinetic levels, with an assessment of the effectiveness and safety of therapy for the female body.

Micronization of progesterone is necessary for improving the pharmacokinetic properties of progestin preparations that increase the chances of favorable pregnancy outcomes and are essential for hormone replacement therapy. A computer analysis of 637 publications on micronized progesterone (MP) made it possible to systematize the results of studies (1) on the pharmacokinetics of MP preparations, (2) the use of MP in therapy for hot flashes, (3) the effect of MP on the central nervous system, (4) the normolipidemic properties of MP, (5) the use of MP to maintain pregnancy and (6) to improve the efficiency of reproductive technologies. Key words: safety issues, micronized progesterone, pregnancy maintenance, Prajisan, pharmacoanalytics

The search for original publications on fundamental and clinical medicine that would produce results of the highest scientific quality represents an urgent need for every medical researcher. Such publications are essential, in particular, for the development of reliable treatment standards. The Englishlanguage resources PUBMED and EMBASE are essential to help in solving this problem. However, there is an obvious problem in assessing the quality of the studies found. The paper formulates a method for analyzing the texts of biomedical publications, which is based on an algorithmic assessment of the emotional modality of medical texts (so-called sentiment analysis). The use of the topological theory of data analysis made it possible to develop a set of high-precision algorithms for identifying 16 types of sentiments (manipulative turns of speech, research without positive results, propaganda, falsification of results, negative personal attitude, aggressiveness of the text, negative emotional background, etc.). On the basis of the developed algorithms, a point scale for assessing the sentiment quality of research was obtained, which we called the "β-score": the higher the β-score, the less the evaluated text contains manipulative language constructions. As a result, the ANTIFAKE system (http://antifake-news.ru) was developed to analyze the sentiment-quality of Englishlanguage scientific texts. An analysis of ~ 20 million abstracts from PUBMED showed that publications with low sentiment quality (β-score <0, that is, that the prevalence of manipulative constructions over meaningful ones) is only 19 %. In the overwhelming majority of thematic headings (27,090 out of 27,840 headings of the MESH system PUBMED), a positive dynamics of sentiment quality of the texts of publications is shown by years). At the same time, as a result of the study, 249 headings were identified with sharply negative dynamics of sentiment quality and with a pronounced increase in manipulative sentiments characteristic of the "yellow" English-language press. These headings include tens of thousands of publications in peer-reviewed journals, which are aimed at (1) legalizing ethically unacceptable practices (euthanasia, perversions, so-called "population control", etc.), (2) discrediting psychiatry as a science, (3) media the war against micronutrients and (4) discrediting evidence-based medicine under the guise of developing the so-called "international standards of evidence-based medicine". In general, the developed system of artificial intelligence allows researchers to filter out pseudoscientific publications, the text of which is overloaded with emotional manipulation and which are published under the guise of "evidence-based standards".

Aim. Sufficient provision of women of reproductive age with omega-3 polyunsaturated fatty acids (PUFA), vitamins and microelements is an important factor in optimizing the course and outcomes of pregnancy. Therefore, in therapeutic practice, methods of non-invasive and rapid assessment of the supply of омега-3-PUFAs in women: docosahexaenoic (DHA), eicosapentaenoic (EPA) acid and synergistic micronutrients are in great demand. Materials and methods. Collection and analysis of data from a cross-sectional study of Russian women of reproductive age (1835 years old, n=1368). Results. A verified 100-point scale for a non-invasive rapid assessment of a woman's status by омега-3-PUFA is proposed. This scale, based on the established correlations between the omega-3 index (% EPA + % DHA in the blood), makes it possible to identify patients with normal values of the omega-3 index in the blood (more than 4%) with a sensitivity of 65% and a selectivity of 88%. Score values less than 60 correspond to an insufficient value of the omega-3 index (sensitivity 81%, selectivity 65%). Conclusion. The correlations established in this study between the reduced supply of omega-3-PUFAs and other micronutrients (vitamins E, K, A, B1, B2, PP, B6, folates, magnesium, selenium, copper and iron) suggest the presence of combined micronutrient deficiencies in women with low value of the score on the developed scale.

Objective: to carry out a systematic computer-assisted analysis of scientific literature on on the relationships between the effects of vitamin and nociception (including the impact of vitamin D deficiency on the development of pain syndrome.Material and methods. For the query “(pain OR nociception) AND (vitamin D OR cholecalciferol OR VITD OR CALCITRIOL OR HYDROXYVITAMIN OR DIHYDROXYVITAMIN OR ALPHACALCIDOL)", 2318 references, including 77 references on alpha-calcidol, were found in the biomedical publications database PubMed. The computer-assisted analysis of this array of publications was carried out using the current big data analysis methods developed within the topological and metric approaches to recognition/classification problems.Result and discussion. A systematic computer-assisted text analysis of 2318 studies on the relationships between nociception and vitamin D showed that the analgesic effects of the vitamin are by anti-inflammatory action and the regulation of serotonergic, dopaminergic, and opioidergic neurotransmission. The lower blood levels of the major vitamin D metabolite 25 (OH)D is a risk factor for decreased pain threshold in myalgia, fibromyalgia, arthralgia, dorsalgia, and a number of neuralgias.Conclusion. In patients with impaired renal conversion of active vitamin D metabolites (especially in the elderly), the efficacy of cholecalciferol-based drugs is reduced, which makes it necessary to use the active forms of vitamin D.

Objective: analysis of the osteoarthritis (OA) comorbidity taking into account the microelement status and genetic polymorphisms of the examined patients, determination of the prospects for the OA prevention and therapy.Material and methods. A cross-sectional study of a multiethnic cohort (n=655, mean age 43±14 years, 95% CI 29–70) formed on the basis of the Institute of Microelements database, was carried out. For all participants, the content of the 62 elements of the Element Periodic Table profile in hair was identified and variants of 120 nucleotide polymorphisms associated with various pathologies were definedResults. The study found that 18 of the 27 ICD-10 diagnoses examined were comorbid with OA. Osteoarthritis was comorbid with pathologies with a pronounced component of inflammation (ulcerative colitis, atherosclerosis, unspecified encephalopathy, obesity, diabetes mellitus, essential (primary) hypertension, urine calculus, acute myocardial infarction, cholelithiasis, etc.). The core of OA comorbidity was established, which included following pathologies: chronic cerebral ischemia, diabetes mellitus, thrombophlebitis, atherosclerosis, cholelithiasis. Seven profiles of the most frequent combinations of these diagnoses were identified. The presence of 2 out of 5 of these pathologies was recorded in 92% of patients with OA (n=50) and only in 2% of control patients (n=600), which corresponded to an extreme increase in the risk of OA (OR 56.3, 95% CI 17.4–181.6, p<10–20). Analysis of the 62 elements profile of the Element Periodic Table content in hair showed that reduced levels of silicon, molybdenum, vanadium and calcium are significantly associated with OA. As a result of studying data on 120 nucleotide polymorphisms, OA was significantly associated with the LPL Ser447Stop CC, LPL N291S AA, NOS3 E298D GG, and MTHFR 677 CC genotypes, which regulate lipid metabolism and inflammation.Conclusion. Based on the obtained results the prospects for the use of chondroitin sulfate and glucosamine sulfate in patients with an increased risk of OA development are shown.

Combined oral contraception and treatment of new coronavirus infection (COVID-19): issues of drug interaction This article examines the interaction of combined oral contraceptives with drugs recommended in the treatment of new coronavirus infection (COVID-19) at the pharmacodynamic and pharmacokinetic levels, with an assessment of the effectiveness and safety of therapy for the female body.

This article discusses the problem of drug interactions between combined oral contraceptives on the example of Belara® (30 μg of ethinyl estradiol + 2 mg of chlormadinone acetate; Gedeon Richter, Hungary) and medications recommended for the treatment of new coronavirus infection (COVID-19) and concomitant disorders at the pharmacodynamic and pharmacokinetic levels with an assessment of the efficacy and safety of therapy for females. We described safe, potentially dangerous, and dangerous combinations of these drugs. Key words: new coronavirus infection (CAVID-19), combined oral contraceptives, antiviral drugs, antibacterial drugs, antiinflammatory drugs, anticoagulants, migraine drugs, antihypertensive drugs, oral hypoglycemic drugs, essential micronutrients, pharmacodynamic and pharmacokinetic interactions

Vitamin B12 (cyanocobalamin) and some of its hydrophilic derivatives are used as antidotes and also to treat megaloblastic anemia, nerve myelination disorders, and liver pathology. This work presents results of a comparative experimental study of cyanocobalamin and its derivatives aquacobalamin and heptamethyl ester of cyanoaquacobyrinic acid. In a model of thiosemicarbazide seizures in rats, aquacobalamin contributed to a lengthening of the seizure latency period while cyanocobalamin contributed to a decrease in the seizure latency period and to a decrease in seizures. Histological study of the brain samples showed that all investigated compounds exhibited an antispasmodic effect as well as neuroprotective and myelinating effects. For the first time it was shown that a derivative of vitamin B12, which has hydrophobic substituents—heptamethyl ester of cyanoaquacobyrinic acid, also exhibits biological activity and, therefore, is of interest for further research. Analysis of changes in the electronic absorption spectra recorded during the interaction of aquacobalamin with thiosemicarbazide indicated possibility of direct interaction of thiosemicarbazide with aquacobalamin.

Introduction. Chondroitin sulfate (CS) and glucosamine sulfate (GS), widely used as chondroprotectors, can maintain the normal functioning of the urinary system but their effect has not been analyzed systematically.Aim: to perform a systematic analysis of the possibilities of using CS and GS in patients with pathology of the kidneys and urinary system.Materials and methods. Predictive analysis of 2,093 publications on the interactions of CS/GS with the functioning of the kidneys and other organs of the urinary system found at the request “(urinary OR bladder OR kidney) AND (glucosamine OR chondroitin)” by methods of the theory of topological data analysis.Results. Disorders of cholesterol and glucosamine metabolism are characteristic of cystitis, glomerular nephritis, urinary tract infections (UTIs), urolithiasis, proteinuria, and formation of diabetic nephropathy. In addition to inhibiting the pro-inflammatory cascade NF-kB, CS/GS contribute to eliminating the deficiency of glycosaminoglycans in the pathology of urothelium, inhibit urolithiasis, inhibit the synthesis of pro-inflammatory nitric oxide NO in macrophages, and modulate O-glycosylation processes.Conclusion. The results of fundamental and clinical studies show that subsidies of CS/GS substances of pharmacological quality per os and CS instillation in the bladder (in particular, in combination with hyaluronic acid) are the means of choice for patients suffering from osteoarthritis and diseases of the urinary system. Highly purified pharmacological CS substances are part of the preparation Chondroguard.

Extracts of Vitex agnus-castus are used to regulate the menstrual cycle, in the treatment of premenstrual tension syndrome, hyperprolactinemia, and infertility. Vitex extracts component analysis showed the presence of such compounds as vitexin, rotundifuran, kastitsin, artemetin and some phytoestrogens. Extracts components are characterized with antiinflammatory, antiproliferative, antioxidant, antimicrobial (particularly antifungal), vasoprotective and analgesic effects. The role of the extracts components in modulation of opioid and dopamine receptors has been described. The paper also reviews estrogen modulating and anti-hyperprolactinemic properties of Vitex extracts

Introduction. The English-language databases PubMed/MEDLINE and Embase are valuable information resources for finding original publications in basic and clinical medicine. Currently, there are no artificial intelligence systems to evaluate the quality of these publications.Aim. Development and testing of a system for sentiment analysis (i.e. analysis of emotional modality) of biomedical publications.Materials and methods. The technique of analysis of the “Big data” of biomedical publications was formulated on the basis of the topological theory of sentiment analysis. Algorithms have been developed that allow for the classification of texts from 16 sentiment classes with 90% accuracy (manipulative speech, research without positive results, propaganda, falsification of results, negative personal attitude, aggressive text, negative emotional background, etc.). Based on the algorithms, a scale for assessing the sentiment quality of research (β-score) is proposed.Results. Abstracts of 19.9 million publications registered in PubMed/MEDLINE over the past 50 years (1970–2019) were analyzed. It was shown that publications with low sentiment quality (the value of the β-score of the text is less than zero, which corresponds to the prevalence of manipulative and negative sentiments in the text) comprise only 18.5% (3.68 out of 19.9 million). The greatest values of the β-score were characterized by publications on sports medicine, systems biology, nutrition, on the use of applied mathematics and data mining in medicine. The rubrication of the entire array of publications by 27,840 headings (MESH-system of PubMed/MEDLINE) indicated an increase in the β-score by years (i.e., the positive dynamics of sentiment quality of the texts of publications) for 27,090 of the studied headings. The most intense positive dynamics was found for research in genetics, physiology, pharmacology, and gerontology. 249 headings with sharply negative dynamics of sentiment quality and with a pronounced increase in the manipulative sentiments characteristic of the tabloid press were highlighted. Separate assessments of international experts are presented that confirm the patterns identified.Conclusion. The proposed artificial intelligence system allows a researcher to make an effective assessment of the sentiment quality of biomedical research papers, filtering out potentially inappropriate publications disguised as “evidence-based”.

The chondroprotectors glucosamine sulfate (GS) and chondroitin sulfate (CS) show a complex anti-inflammatory effect and therefore may be used in the therapy of many diseases concurrent with osteoarthritis. Objective: to carry out a systematic analysis of the relationship between the molecular pathophysiology of tenosynovitis and the potential mechanisms of pathogenic action of CS/GS in this disease. Material and methods. The texts of 15 097 publications were systemized using the current methods for topographic big data analysis, which had been developed as part of topological and metric approaches to recognition/classification problems. Results and discussion. The investigators created a map showing the molecular pathophysiology of tendosynovitis and including 15 molecular mechanisms and 27 comorbidities and identified mechanisms, through which GS/CS could prevent the development of tenosynovitis, such as inhibition of the effects of proinflammatory cytokines (IL-1, IL-8, γ -interferon, and TNF- α ), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein, NLRP3 inflammasome, NF- κ B and JAK/STAT signaling pathways, and O-glucosamination of proteome proteins. To date, no randomized clinical or cohort (non-interventional) studies of the effects of CS/GS have been conducted in patients with tendosynovitis and comorbidities. However, preclinical studies of GS and CS in the treatment of tendinopathies showed that the drugs had analgesic properties, alleviated chronic inflammation and edema, and improved the maturation of collagen bundles and therefore the mechanical properties of connective tissue in the tendons and ligaments. Conclusion. The experimental and clinical studies indicate that pharmaceutical-grade GS/CS preparations of high standardization are promising in treating tenosynovitis.