Iron deposits in tissues (hemosiderosis) accompany various diseases of the liver and pancreas. Overload of the liver with iron occurs due to (1) a diet with excess saturated fats, which provoke inflammation of the liver, (2) slowdown and stagnation of blood flow in the area of the portal vein (physical inactivity, obesity, alcoholism, etc), (3) uncontrolled and long-term use of iron supplements (primarily based on inorganic forms - sulfates, oxides, hydroxides of iron, etc.), (4) hereditary diseases (hemochromatosis). Patients with liver overload with iron require not only correction of diet and lifestyle (including physical activity), but also special therapy using effective and safe drugs. To study the effect of excess iron on the body and search for the most appropriate therapy for hemosiderosis, special models of liver overload with iron have been developed in pharmacology. The degree of iron overload and the rate of hemosiderosis formation in models can be slowed down by the addition of micronutrients with hepatoprotective properties (vitamins A, C) and accelerated by the addition of saturated fat and/or fructose to the diet.

Palm oil is a component of most food products, characterized by a high content of palmitic and oleic acids, an excess of which leads to the formation of tripalmitins, practically do not respond to enzymatic hydrolysis by lipoprotein lipase and predetermine the development of obesity, type 2 diabetes mellitus and atherosclerosis. This paper presents the results of a study of the drug Laennek, produced on the basis of standardized hydrolysates of the human placenta (HRP). The use of HRP under the influence of excessive consumption of palm oil in the diet led to a significant decrease in markers of liver dysfunction (ALT), which increase with an enriched diet of refined palm oil (bilirubin, total protein, ALT, AST). The hepatoprotective effect of Laennek was confirmed by the results of histological and biochemical studies indicating a decrease in the severity and prevalence of fatty liver dystrophy.

Today, it is difficult to overestimate the new directions in the pharmacotherapy of peripheral T-cell lymphomas (PTCL): immunotherapy, including adoptive, targeted therapy and chemotherapy. However, there are few biomarkers that predict response to therapy. A big problem is patients with refractory and recurrent PTCL who do not respond to such therapy or demonstrate adverse events, which makes it important to personalize therapy and search for predictive markers, followed by thorough analytical and clinical validation. The literature highlights the importance of using biomarkers obtained from whole exome sequencing and tumor transcriptome sequencing. The review discusses the T cell ontogenesis, as well as the possibilities of personalization of anticancer drugs such as azacitidine, duvelisib, romidepsin, and bortezomib for the treatment of refractory or recurrent PTCL.

High-throughput next-generation sequencing (NGS) technologies such as whole exome sequencing (WES) and bulk RNA sequencing (RNA-seq) allow identification of the new biomarkers of response and resistance to antitumor therapy. Retrospective studies have shown that the state of the tumor microenvironment (TME), identified via RNA-seq, is an independent prognostic and predictive biomarker. WES and RNA-seq technologies, along with classical immunohistochemistry, provide a comprehensive analysis of the tumor and TME. Affordability of high-throughput sequencing will enable personalization of antitumor pharmacotherapy.

Objectives. To systematize publications on drugs based on cytidine diphosphocholine (CDP-choline). Materials and methods. Systematic computer analysis of all currently available publications on CDPcholine (1750 publications in PubMed) using topological analysis theory for big data. Results. CDP-choline is required for acetylcholine biosynthesis, phospholipid metabolism, and DNA methylation. This article sequentially considers the effects of CDP-choline on acetylcholinergic and other types of neurotransmission and the anti-inflammatory and neuroprotective effects of CDP-choline, as well as the influences of this molecule on fat metabolism and gene expression in the context of the postgenomic paradigm (particularly elevated expression of nicotinic and muscarinic acetylcholine receptors). Results from basic and clinical studies of CDP-choline in the treatment of cognitive impairments associated with cerebral ischemia and neurodegeneration are presented. Conclusions. The pharmacological effects of CDP-choline are realized via multiple molecular mechanisms contributing to the nootropic actions of this molecule.

Lithium salts have been the mainstay of treatment for bipolar disorder for more than 50 years, since approval by the FDA in 1970 for the treatment of this pathology. A variety of the molecular mechanisms of action of lithium have been well studied, primarily inhibition of the enzymes glycogen synthase 3β and inositol monophosphatase, with subsequent activation of cascades of cellular reactions, including induction of brain-derived neurotrophic factor and antiapoptotic proteins and suppression of calcium-dependent activation of apoptosis. Research over the last decade has focused on the effects of lithium on the regulation of autophagy and the accumulation of pathological proteins such as amyloid β and tau protein in neurons. Lithium is also thought to induce telomere elongation and to increase telomerase activity. Clinical studies of lithium have addressed the potential for its use for the prevention and treatment of neurodegenerative diseases, primarily Alzheimer’s disease, with increasing emphasis on the use of lithium microdoses. A separate scientific problem is the search for safe and effective lithium salts using methods including chemoreactome analysis.

Hepatoprotectors are necessary for the treatment of alcoholic and non-alcoholic (including medicinal) liver damage. This paper presents the results of a study of the Laennec hepatoprotector, produced on the basis of pharmaceutically standardized human placental hydrolysates (HPH). The use of HSP in toxic liver damage with alcohol or paracetamol led to a significant decrease in markers of liver dysfunction (AST, ALT, bilirubin, MDA), which increase when the models are reproduced. The hepatoprotective effect of Laennec was confi rmed by the results of histological studies, indicating a reduction in infl ammation and preservation of the liver parenchyma. Histological studies also indicated the nephroprotective and cardioprotective effects of Laennec in liver damage with both alcohol and paracetamol.

OBJECTIVE:Systematization of the array of publications on cytidyldiphosphocholine (CDP-choline).MATERIAL AND METHODS:Systematic computer analysis of all currently available publications on CDP-choline (1750 publications in PUBMED) using the topological theory of big data analysis.RESULTS:CDP-choline is essential for acetylcholine biosynthesis, phospholipid metabolism, and DNA methylation. The article describes the effects of CDP-choline on acetylcholinergic and other types of neurotransmission, anti-inflammatory, neuroprotective and neurotrophic effects of CDP-choline. Also, the paper presents the effects of the molecule on lipid metabolism and gene expression within the post-genomic paradigm (in particular, an increase in the expression of nicotinic and muscarinic acetylcholine receptors). The results of fundamental and clinical studies of CDP-choline in the treatment of cognitive impairments associated with cerebral ischemia and neurodegeneration are presented.CONCLUSION:The pharmacological effects of CDP-choline are mediated through multiple molecular mechanisms that contribute to the nootropic action of this molecule.

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".

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.

Objective: to establish the molecular mechanisms of interaction of cytidine-diphosphocholine choline (CDP-choline) with other agents used to treat chronic cerebral ischemia (CCI) to increase the effectiveness of the therapy..Material and methods. A chemoreactom analysis of CDP-choline, betahistine, ethyl-methyl-hydroxypyridine succinate (EMHPS), vinpocetine, and nicergoline was conducted using the computational methods of the theory of topological analysis of chemographs. Results and discussion. The profiles of the pharmacological action of molecules are described, including the accumulation in tissues, pharmacokinetic and pharmacodynamic parameters, the effect on the metabolome and proteome, the survival of neurons during glutamate stress. The mechanisms of the synergistic action of CDP-choline and EMHPS were discovered, including: 1) inhibition of the activation of the pro-inflammatory factor NF-κB; 2) decrease in the procoagulant profile; 3) decrease in glutamate excitotoxicity secondary to improved oxygen metabolism. These effects result in conjunction with at least 25 proteins of the human proteome.Conclusion. CDP-choline supports cholinergic neurotransmission and is used in the treatment of vascular pathologies of the brain. The cholinergic effect of CDP-choline is enhanced by the anti-inflammatory, anticoagulant, and neuroprotective action of both the molecule itself and synergistic molecules (in particular, EMHPS).

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.

Objective: to investigate the effect of dexketoprofen on the severity of seizures on a rat model of primary generalized seizures caused by thiosemicarbazide; to evaluate the neuroprotective effect of the drug.Material and methods. The investigation was conducted on 72 male albino rats weighing 200–300 g. The animals were given dexketoprofen and/or comparison drugs (gabapentin, sodium valproate) for 5 days, after which the seizure model was reproduced. The effects of the drugs were evaluated from a set of neurological tests and the results of a histopathological examination of the brain.Results and discussion. Dexketoprofen reduced the severity, duration, and number of primary generalized seizures and potentiated the anticonvulsant effects of gabapentin and sodium valproate. Histopathological and morphometric examinations of the rat brain showed that dexketoprofen inhibited the formation of irreversible neuronal changes (27.2%; control, 55.7%), by transferring them into reversible changes (47.7%; control, 21.8%).Conclusion. The investigation made it possible to conclude that dexketoprofen had a moderate neuroprotective effect neurologically and morphometrically verified.

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”.