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Dmitrij A Sychev,1 Ghulam Md Ashraf,2 Andrey A Svistunov,3 Maksim L Maksimov,4 Vadim V Tarasov,3 Vladimir N Chubarev,3 Vitalij A Otdelenov,1 Natal’ja P Denisenko,1 George E Barreto,5,6 Gjumrakch Aliev7–9 1Russian Medical Academy of Postgraduate Education Studies, Moscow, Russia; 2King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; 3Sechenov First Moscow State Medical University, Moscow, Russia; 4Branch Campus of the Federal State Budgetary Educational Institution of Further Professional Education «Russian Medical Academy of Continuous Professional Education» of the Ministry of Healthcare of the Russian Federation, Kazan State Medical Academy, Volga Region, Kazan, Russia; 5Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia; 6Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile; 7GALLY International Biomedical Research Consulting LLC, San Antonio, TX, USA; 8School of Health Science and Healthcare Administration, University of Atlanta, Johns Creek, GA, USA; 9Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, Russia Abstract: Cytochrome (CYP) 450 isoenzymes are the basic enzymes involved in Phase I biotransformation. The most important role in biotransformation belongs to CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2. Inhibition and induction of CYP isoenzymes caused by drugs are important and clinically relevant pharmacokinetic mechanisms of drug interaction. Investigation of the activity of CYP isoenzymes by using phenotyping methods (such as the determination of the concentration of specific substrates and metabolites in biological fluids) during drug administration provides the prediction of negative side effects caused by drug interaction. In clinical practice, the process of phenotyping of CYP isoenzymes and some endogenous substrates in the ratio of cortisol to 6β-hydroxycortisol in urine for the evaluation of CYP3A4 activity has been deemed to be a quite promising, safe and minimally invasive method for patients nowadays. Keywords: cytochrome CYP450, drug interaction, drug metabolism, phenotyping

Cancer is considered the most important clinical, social and economic issue regarding cause‑specific disability‑adjusted life years among all human pathologies. Exogenous, endogenous and individual factors, including genetic predisposition, participate in cancer triggering. Telomeres are specific DNA structures positioned at the end of chromosomes and consist of repetitive nucleotide sequences, which, together with shelterin proteins, facilitate the maintenance of chromosome stability, while protecting them from genomic erosion. Even though the connection between telomere status and carcinogenesis has been identified, the absence of a universal or even a cancer‑specific trend renders consent even more complex. It is indicative that both short and long telomere lengths have been associated with a high risk of cancer incidence. When evaluating risk associations between cancer and telomere length, a disparity appears to emerge. Even though shorter telomeres have been adopted as a marker of poorer health status and an older biological age, longer telomeres due to increased cell growth potential are associated with the acquirement of cancer‑initiating somatic mutations. Therefore, the present review aimed to comprehensively present the multifaceted pattern of telomere length and cancer incidence association.

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID)., Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration., Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022., Exposures: Symptomatic SARS-CoV-2 infection., Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age., Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months., Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

Background: Previous studies assessing the prevalence of COVID-19 sequelae in adults and children were performed in the absence of an agreed definition. We investigated prevalence of post-COVID-19 condition (PCC) (WHO definition), at 6- and 12-months follow-up, amongst previously hospitalised adults and children and assessed risk factors., Methods: Prospective cohort study of children and adults with confirmed COVID-19 in Moscow, hospitalised between April and August, 2020. Two follow-up telephone interviews, using the International Severe Acute Respiratory and Emerging Infection Consortium survey, were performed at 6 and 12 months after discharge., Results: One thousand thirteen of 2509 (40%) of adults and 360 of 849 (42%) of children discharged participated in both the 6- and 12-month follow-ups. PCC prevalence was 50% (95% CI 47-53) in adults and 20% (95% CI 16-24) in children at 6 months, with decline to 34% (95% CI 31-37) and 11% (95% CI 8-14), respectively, at 12 months. In adults, female sex was associated with PCC at 6- and 12-month follow-up (OR 2.04, 95% CI 1.57 to 2.65) and (OR 2.04, 1.54 to 2.69), respectively. Pre-existing hypertension (OR 1.42, 1.04 to 1.94) was associated with post-COVID-19 condition at 12 months. In children, neurological comorbidities were associated with PCC both at 6 months (OR 4.38, 1.36 to 15.67) and 12 months (OR 8.96, 2.55 to 34.82) while allergic respiratory diseases were associated at 12 months (OR 2.66, 1.04 to 6.47)., Conclusions: Although prevalence of PCC declined one year after discharge, one in three adults and one in ten children experienced ongoing sequelae. In adults, females and persons with pre-existing hypertension, and in children, persons with neurological comorbidities or allergic respiratory diseases are at higher risk of PCC., (© 2022. The Author(s).)

Objectives: The present study investigated the stability of furosemide under space-flight conditions on board the International Space Station, as well as its pharmacokinetics and pharmacodynamics under conditions simulating exposure to some space-flight factors., Methods: Quantitative analysis of furosemide tablets by HPLC was performed before spaceflight (background), then after six months storage under normal ground conditions (control) and under spaceflight conditions (SF). The pharmacokinetics and pharmacodynamics of furosemide were studied in six healthy volunteers after a single oral dose of 40 mg under normal conditions (background) and under anti-orthostatic hypokinesia (ANOH)., Results: Quantitative content of furosemide in tablets before SF was 40.19 ± 0.28 mg (100.47 ± 0.71%), after 6 months storage: under normal conditions (control) - 39.9 ± 0.39 mg (99.73 ± 0.98%), under SF - 39.24 ± 0.72 mg (98.11 ± 1.80%), which was within the prescribed limits. Studying basic hemodynamic parameters showed that in ANOH conditions 6 h after furosemide administration there was a statistically significant increase of the stroke volume (SV) (+36.5 Δ%), a tendency for increasing of the stroke index (SI) (+36.5 Δ%) and decreasing of the total peripheral resistance (TPR) (-21.9 Δ%) compared to baseline study., Conclusions: It has been established that various factors of space flight (overloading, excessive vibration, microgravity, etc.) do not negatively influence the stability of furosemide in tablet form during storage for 6 months on board the International Space Station., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Aim: To establish the role of the main risk factors and endocrine cells of the antrum of the stomach producing motilin (M-cells) in the occurrence of cholelithiasis., Materials and Methods: The first group included 122 patients with cholelithiasis. The second group consisted of 30 healthy individuals who underwent medical examination. The groups were matched for gender and age. The work analyzed anamnestic, biochemical and anthropometric data. All patients underwent esophagogastroduodenoscopy with targeted biopsy of the mucous membrane from the antrum. Biopsies were subjected to cytological and immunohistochemical studies in order to verify Helicobacter pylori and estimate the number of M-cells., Results: Patients with cholelithiasis more often belonged to the group of people of mental labor, had low physical activity, were committed to inappropriate nutrition and more often indicated the presence of aggravated heredity for cholelithiasis. Patients with gallstone disease had higher body mass index, waist volume, total cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, lower high-density lipoprotein cholesterol, H. pylori infection was more often verified and M-cell hypoplasia in the mucous membrane was established. stomach in comparison with the representatives of the second group., Conclusion: Our results suggest that certain external factors, nutritional characteristics of the metabolic syndrome components, hypoplasia of M-cells in the gastric mucosa are important factors in the formation of calculi in the gallbladder.

In view of the significant role of H 2 S in brain functioning, it is proposed that H 2 S may also possess protective effects against adverse effects of neurotoxicants. Therefore, the objective of the present review is to discuss the neuroprotective effects of H 2 S against toxicity of a wide spectrum of endogenous and exogenous agents involved in the pathogenesis of neurological diseases as etiological factors or key players in disease pathogenesis. Generally, the existing data demonstrate that H 2 S possesses neuroprotective effects upon exposure to endogenous (amyloid β, glucose, and advanced-glycation end-products, homocysteine, lipopolysaccharide, and ammonia) and exogenous (alcohol, formaldehyde, acrylonitrile, metals, 6-hydroxydopamine, as well as 1-methyl-4-phenyl- 1,2,3,6- tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenyl pyridine ion (MPP)) neurotoxicants. On the one hand, neuroprotective effects are mediated by S-sulfhydration of key regulators of antioxidant (Sirt1, Nrf2) and inflammatory response (NF-κB), resulting in the modulation of the downstream signaling, such as SIRT1/TORC1/CREB/BDNF-TrkB, Nrf2/ARE/HO-1, or other pathways. On the other hand, H 2 S appears to possess a direct detoxicative effect by binding endogenous (ROS, AGEs, Aβ) and exogenous (MeHg) neurotoxicants, thus reducing their toxicity. Moreover, the alteration of H 2 S metabolism through the inhibition of H 2 S-synthetizing enzymes in the brain (CBS, 3-MST) may be considered a significant mechanism of neurotoxicity. Taken together, the existing data indicate that the modulation of cerebral H 2 S metabolism may be used as a neuroprotective strategy to counteract neurotoxicity of a wide spectrum of endogenous and exogenous neurotoxicants associated with neurodegeneration (Alzheimer's and Parkinson's disease), fetal alcohol syndrome, hepatic encephalopathy, environmental neurotoxicant exposure, etc. In this particular case, modulation of H 2 S-synthetizing enzymes or the use of H 2 S-releasing drugs should be considered as the potential tools, although the particular efficiency and safety of such interventions are to be addressed in further studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The article presents the views on dyspepsia in world practice, data on the difficulties of diagnosis and the problem of the effectiveness of various therapy regimens. Particular attention is paid to the use of fixed forms of drugs for functional dyspepsia, in particular Omez DSR.

Objectives: To study the pharmacokinetics and relative bioavailability of drugs of different chemical structure and pharmacological action under conditions simulating the effects of some factors of spaceflight, as well as the peculiarities of the pharmacokinetics of acetaminophen under long-term spaceflight conditions., Methods: The pharmacokinetics of verapamil (n=8), propranolol (n=8), etacizine (n=9), furosemide (n=6), and acetaminophen (n=7) in healthy volunteers after a single oral administration under normal conditions (background) and under antiorthostatic hypokinesia (ANOH), the pharmacokinetics of acetaminophen in spaceflight members under normal ground conditions (background) (n=8) and under prolonged spaceflight conditions (SF) (n=5) were studied., Results: The stay of volunteers under antiorthostatic hypokinesia had different effects on the pharmacokinetics and bioavailability of drugs: Compared to background, there was a decreasing trend in V z for verapamil (-54 Δ%), furosemide (-20 Δ%), propranolol (-8 Δ%), and acetaminophen (-9 Δ%), but a statistically significant increase in V z was found for etacizine (+39 Δ%); there was an increasing trend in Cl t for propranolol (+13 Δ%) and acetaminophen (+16 Δ%), and a decreasing trend in Cl t for etacizine, verapamil, and furosemide (-22, -23 and -9 Δ% respectively) in ANOH. The relative bioavailability of etacizine, verapamil, and furosemide in ANOH increased compared to background (+40, +23 and +13 Δ%, respectively), propranolol and acetaminophen decreased (-5 and -12 Δ% accordingly). The relative rate of absorption of etacizine and furosemide in ANOH decreased (-19 and -20 Δ%, respectively) while that of verapamil, propranolol, and acetaminophen increased (+42, +58 and +26 Δ%, respectively). A statistically significant decrease in AUC 0-∞ (-57 Δ%), C max (-53 Δ%), relative bioavailability of acetaminophen (-52 Δ%) and a sharp increase in Cl t (+147 Δ%), T max (+131 Δ%) as well as a trend towards a significant decrease in T 1/2 (-53 Δ%), MRT (-36 Δ%) and a moderate increase in V z (+24 Δ%) were found under control compared to background. Unidirectional changes in AUC 0-∞ , Cl t , T 1/2 , MRT and relative bioavailability of acetaminophen, which are more pronounced in SF and opposite dynamics for C max , T max , V z were found in ANOH and SP compared to background studies., Conclusions: The data obtained allow recommending the studied drugs for rational pharmacotherapy in the possible development of cardiovascular disease in manned spaceflight., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

The self-assembly of peptides is a key direction for fabrication of advanced materials. Novel approaches for fine tuning of macroscopic and microscopic properties of peptide self-assemblies are of a high demand for constructing biomaterials with desired properties. In this work, while studying the kinetics of the Fmoc-Diphenylalanine (Fmoc-FF) dipeptide self-assembly using the Thioflavin T (ThT) dye, we observed that the presence of ThT strongly modifies structural and mechanical properties of the Fmoc-FF hydrogel. Notably, the presence of ThT resulted in a tenfold increase of the gelation time and in the formation of short and dense fibers in the hydrogel. As a result of these morphological alteration higher thermal stability, and most important, tenfold increase of the hydrogel rigidity was achieved. Hence, ThT not only slowed the kinetics of the Fmoc-FF hydrogel formation, but also strongly enhanced its mechanical properties. In this study, we provide a detailed description of the ThT effect on the hydrogel properties and suggest the mechanisms for this phenomenon, paving the way for the novel approach to the control of the peptide hydrogels' micro- and macroscale properties., (© 2021 Wiley-VCH GmbH.)

Background: This review summarizes recent findings in molecular biology and neuroimaging and their applicability to the classification and identification of depression. We discuss whether there is reliable evidence that could become a basis for biomarkers or subtyping that may enhance our understanding of the biological foundations of depression and may be useful for clinical practice with respect to diagnosis and prognosis as well as the selection of treatments., Objective: The purpose of this investigation is to present molecular mechanisms that contribute to different origins of depressions that could prove useful in the daily psychiatric clinic-based practices., Methods: The authors have analyzed and summarized electronic publications available in PubMed, Science Direct, Google Scholar, and Scopus., Results: The introduction of molecular diagnostic methods into medical practice is a promising method to improve the accuracy of the diagnosis of depression in clinical settings. The literature analysis revealed structural changes in some areas of the brain, its neuroplasticity, as well as changes at the molecular, epigenetic, and genetic levels. However, there are no current reliable biomarkers for differential diagnosis of the types and subtypes of depression., Conclusion: Major depressive disorder is a biologically and genetically heterogeneous disorder. Given its complexity, subtyping is worthwhile to identify biological bases of conditions. The literature review provides ample findings that reveal possible underlying biological mechanisms associated with atypical and melancholic depression. Additional focused research should be continued with respect to the molecular and genetic biology of different types of depression. There already are promising findings, but additional research to define biologically based depressive subtypes is needed and worthwhile., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The long-term sequalae of COVID-19 remain poorly characterized. We assessed persistent symptoms in previously hospitalized patients with COVID-19 and assessed potential risk factors., Methods: Data were collected from patients discharged from 4 hospitals in Moscow, Russia between 8 April and 10 July 2020. Participants were interviewed via telephone using an ISARIC Long-term Follow-up Study questionnaire., Results: 2,649 of 4755 (56%) discharged patients were successfully evaluated, at median 218 (IQR 200, 236) days post-discharge. COVID-19 diagnosis was clinical in 1291 and molecular in 1358. Most cases were mild, but 902 (34%) required supplemental oxygen and 68 (2.6%) needed ventilatory support. Median age was 56 years (IQR 46, 66) and 1,353 (51.1%) were women. Persistent symptoms were reported by 1247 (47.1%) participants, with fatigue (21.2%), shortness of breath (14.5%) and forgetfulness (9.1%) the most common symptoms and chronic fatigue (25%) and respiratory (17.2%) the most common symptom categories. Female sex was associated with any persistent symptom category OR 1.83 (95% CI 1.55 to 2.17) with association being strongest for dermatological (3.26, 2.36 to 4.57) symptoms. Asthma and chronic pulmonary disease were not associated with persistent symptoms overall, but asthma was associated with neurological (1.95, 1.25 to 2.98) and mood and behavioural changes (2.02, 1.24 to 3.18), and chronic pulmonary disease was associated with chronic fatigue (1.68, 1.21 to 2.32)., Conclusions: Almost half of adults admitted to hospital due to COVID-19 reported persistent symptoms 6 to 8 months after discharge. Fatigue and respiratory symptoms were most common, and female sex was associated with persistent symptoms., (© 2021 John Wiley & Sons Ltd.)

Cell aggregates, including sheets and spheroids, represent a simple yet powerful model system to study both biochemical and biophysical intercellular interactions. However, it is becoming evident that, although the mechanical properties and behavior of multicellular structures share some similarities with individual cells, yet distinct differences are observed in some principal aspects. The description of mechanical phenomena at the level of multicellular model systems is a necessary step for understanding tissue mechanics and its fundamental principles in health and disease. Both cell sheets and spheroids are used in tissue engineering, and the modulation of mechanical properties of cell constructs is a promising tool for regenerative medicine. Here, we review the data on mechanical characterization of cell sheets and spheroids, focusing both on advances in the measurement techniques and current understanding of the subject. The reviewed material suggest that interplay between the ECM, intercellular junctions, and cellular contractility determines the behavior and mechanical properties of the cell aggregates., (© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2021.)

Background: The epidemiology, clinical course, and outcomes of patients with coronavirus disease 2019 (COVID-19) in the Russian population are unknown. Information on the differences between laboratory-confirmed and clinically diagnosed COVID-19 in real-life settings is lacking., Methods: We extracted data from the medical records of adult patients who were consecutively admitted for suspected COVID-19 infection in Moscow between 8 April and 28 May 2020., Results: Of the 4261 patients hospitalized for suspected COVID-19, outcomes were available for 3480 patients (median age, 56 years; interquartile range, 45-66). The most common comorbidities were hypertension, obesity, chronic cardiovascular disease, and diabetes. Half of the patients (n = 1728) had a positive reverse transcriptase-polymerase chain reaction (RT-PCR), while 1748 had a negative RT-PCR but had clinical symptoms and characteristic computed tomography signs suggestive of COVID-19. No significant differences in frequency of symptoms, laboratory test results, and risk factors for in-hospital mortality were found between those exclusively clinically diagnosed or with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR. In a multivariable logistic regression model the following were associated with in-hospital mortality: older age (per 1-year increase; odds ratio, 1.05; 95% confidence interval, 1.03-1.06), male sex (1.71; 1.24-2.37), chronic kidney disease (2.99; 1.89-4.64), diabetes (2.1; 1.46-2.99), chronic cardiovascular disease (1.78; 1.24-2.57), and dementia (2.73; 1.34-5.47)., Conclusions: Age, male sex, and chronic comorbidities were risk factors for in-hospital mortality. The combination of clinical features was sufficient to diagnose COVID-19 infection, indicating that laboratory testing is not critical in real-life clinical practice., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Lactoferrin (Lf) possesses various biological properties and therapeutic potentials being a perspective anti-inflammatory, antibacterial, antiviral, antioxidant, antitumor, and immunomodulatory agent. A significant body of literature has also demonstrated that Lf modulates regenerative processes in different anatomical structures, such as bone, cartilage, skin, mucosa, cornea, tendon, vasculature, and adipose tissue. Hence, this review collected and analyzed the data on the regenerative effects of Lf, as well as paid specific attention to their molecular basis. Furthermore, tissue and condition-specific activities of different Lf types as well as problems of their delivery to the targeted organs were discussed. The authors strongly hope that this review will stimulate researchers to focus on the highlighted topics thus accelerating the progress of Lf's wider clinical application., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The objective of the present study was to evaluate of serum metal levels in COVID-19 patients with different disease severity, and to investigate the independent association between serum metal profile and markers of lung damage. The cohort of COVID-19 patients consisted of groups of subjects with mild, moderate, and severe illness, 50 examinees each. Forty-four healthy subjects of the respective age were involved in the current study as the control group. Serum metal levels were evaluated using inductively-coupled plasma mass-spectrometry. Examination of COVID-19 patients demonstrated that heart rate, respiratory rate, body temperature, C-reactive protein levels, as well as lung damage increased significantly with COVID-19 severity, whereas SpO 2 decreased gradually. Increasing COVID-19 severity was also associated with a significant gradual decrease in serum Ca, Fe, Se, Zn levels as compared to controls, whereas serum Cu and especially Cu/Zn ratio were elevated. No significant group differences in serum Mg and Mn levels were observed. Serum Ca, Fe, Se, Zn correlated positively with SpO 2 , being inversely associated with fever, lung damage, and C-reactive protein concentrations. Opposite correlations were observed for Cu and Cu/Zn ratio. In regression models, serum Se levels were inversely associated with lung damage independently of other markers of disease severity, anthropometric, biochemical, and hemostatic parameters. Cu/Zn ratio was also considered as a significant predictor of lower SpO 2 in adjusted regression models. Taken together, these findings demonstrated that metal metabolism significantly interferes with COVID-19 pathogenesis, although the causal relations as well as precise mechanisms are yet to be characterized.

To date, a lot of nanotechnological optitions are available for targeted drug delivery. Extracellular vesicles (EVs) are membrane structures that cells use for storage, transport, communication, and signaling. Recent research has focused on EVs as natural nanoparticles for drug delivery. This review sheds light on the application of EVs in cancer therapy, such as targeted chemotherapy, gene therapy, and vaccine development. Aspects of biogenesis, isolation, targeting, and loading of EVs are discussed in detail., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Modern medicine has provided considerable knowledge of the pathophysiology of mental disorders at the body, systemic, organ and neurochemical levels of the biological organization of the body. Modern clinical diagnostics of depression have some problems, that is why psychiatric society makes use of diagnostics and taxonomy of different types of depression by implemention of modern molecular biomarkers in diagnostic procedures. But up to now, there are no reliable biomarkers of major depressive disorder (MDD) and other types of depression., Objective: The purpose of this review is to find fundamentals in pathological mechanisms of depression, which could be a basis for development of molecular and genetic biomarkers, being the most feasible for clinical use., Method: This review summarizes the published data using PubMed, Science Direct, Google Scholar and Scopus., Results: In this review, we summarized and discussed findings in molecular biology, genetics, neuroplasticity, neurotransmitters, and neuroimaging that could increase our understanding of the biological foundations of depression and show new directions for the development of reliable biomarkers. We did not find any molecular and genetic biomarker approved for the clinic. But the Genome-Wide Association Study method promises some progress in the development of biomarkers based on SNP in the future. Epigenetic factors also are a promising target for biomarkers. We have found some differences in the etiology of different types of atypical and melancholic depression. This knowledge could be the basis for development of biomarkers for clinical practice in diagnosis, prognosis and selection of treatment., Conclusion: Depression is not a monoetiological disease. Many pathological mechanisms are involved in depression, thus up to now, there is no approved and reliable biomarker for diagnosis, prognosis and correction of treatment of depression. The structural and functional complexity of the brain, the lack of invasive technology, poor correlations between genetic and clinical manifestation of depression, imperfect psychiatric classification and taxonomy of subtypes of disease are the main causes of this situation. One of the possible ways to come over this situation can be to pay attention to the trigger mechanism of disease and its subtypes. Researchers and clinicians should focus their efforts on searching the trigger mechanism of depression and different types of it . HPA axis can be a candidate for such trigger in depression caused by stress, because it influences the main branches of disease: neuroinflammation, activity of biogenic amines, oxidative and nitrosative stress, epigenetic factors, metabolomics, etc. But before we shall find any trigger mechanism, we need to create complex biomarkers reflecting genetic, epigenetic, metabolomics and other pathological changes in different types of depression. Recently the most encouraging results have been obtained from genetics and neuroimaging. Continuing research in these areas should be forced by using computational, statistical and systems biology approaches, which can allow to obtain more knowledge about the neurobiology of depression. In order to obtain clinically useful tests, search for biomarkers should use appropriate research methodologies with increasing samples and identifying more homogeneous groups of depressed patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This article examines issues related to COVID-19 inoculations for children. The bulk of the official COVID-19-attributed deaths per capita occur in the elderly with high comorbidities, and the COVID-19 attributed deaths per capita are negligible in children. The bulk of the normalized post-inoculation deaths also occur in the elderly with high comorbidities, while the normalized post-inoculation deaths are small, but not negligible, in children. Clinical trials for these inoculations were very short-term (a few months), had samples not representative of the total population, and for adolescents/children, had poor predictive power because of their small size. Further, the clinical trials did not address changes in biomarkers that could serve as early warning indicators of elevated predisposition to serious diseases. Most importantly, the clinical trials did not address long-term effects that, if serious, would be borne by children/adolescents for potentially decades. A novel best-case scenario cost-benefit analysis showed very conservatively that there are five times the number of deaths attributable to each inoculation vs those attributable to COVID-19 in the most vulnerable 65+ demographic. The risk of death from COVID-19 decreases drastically as age decreases, and the longer-term effects of the inoculations on lower age groups will increase their risk-benefit ratio, perhaps substantially., Competing Interests: The authors declare that they have no competing interests, (© 2021 The Author(s).)

Aim to determine the efficacy of drug aminodihydrophthalazinedione sodium (Galavit) for prevention of progression of the coronavirus infection pulmonary complications: acceleration of regression of pulmonary infiltrates and resolution of COVID-induced pneumonia. 22 patients with medium and severe COVID-induced pneumonia were included in the study. The study included 8 men and 14 women, the average age was 62.17.4 years. Patients with more than one adverse prognostic factor made 82%. Average volume of pulmonary tissue affection (computer tomography CT-2, 2550% of lung volume) was registered in 13 (59.1%) patients, significant volume (CT-3, 5075% of lung volume), in 9 (40.9%) patients. All patients had progressive respiratory failure manifestations due to hypoxemia and related diseases. Aminodihydrophthalazinedione sodium was administered for 714 days from the beginning of disease, at the end of the course of standard complex therapy, in case of preservation of signs of intoxication, negative dynamics according to computer tomography data. Administration of aminodihydrophthalazinedione sodium had a positive effect on the dynamics of clinical scores. The progression of respiratory failure was halted and there was an increase in SpO2 values. According to the control computer tomography data the stabilization of the pulmonary parenchyma affection degree was noted, as well as reduction of the size of the compacted areas in the pulmonary tissue and formation of the picture of organising pneumonia that contributed to reduction of respiratory failure grade. The use of aminodihydrophthalazinedione sodium in complex therapy of COVID-induced pneumonia has a modulating effect on the immune system, prevents the progression of pulmonary tissue affection, promotes regression of infiltration foci, preventing the development of excessive pneumofibrosis and the progression of respiratory failure.

This study aimed to examine the effects of diallyl trisulfide (DATS), the most potent polysulfide derived from garlic, on metabolic syndrome and myocardial function in rats with metabolic syndrome (MetS). For that purpose, we used 36 male Wistar albino rats divided into control rats, rats with MetS and MetS rats treated with 40 mg/kg of DATS every second day for 3 weeks. In the first part, we studied the impact of DATS on MetS control and found that DATS significantly raised H 2 S, decreased homocysteine and glucose levels and enhanced lipid and antioxidative, while reducing prooxidative parameters. Additionally, this polysulfide improved cardiac function. In the second part, we investigated the impact of DATS on ex vivo induced ischemia/reperfusion (I/R) heart injury and found that DATS consumption significantly improved cardiodynamic parameters and prevented oxidative and histo-architectural variation in the heart. In addition, DATS significantly increased relative gene expression of eNOS, SOD-1 and -2, Bcl-2 and decreased relative gene expression of NF-κB, IL-17A, Bax, and caspases-3 and -9. Taken together, the data show that DATS can effectively mitigate MetS and have protective effects against ex vivo induced myocardial I/R injury in MetS rat.

Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease - 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. The clinical manifestations of this disease are pneumonia, lung injury, inflammation, and severe acute respiratory syndrome (SARS). Currently, there is no vaccine or effective pharmacological agents available for the prevention/treatment of SARS-CoV2 infections. Moreover, development of a suitable vaccine is a challenging task due to antibody-dependent enhancement (ADE) and Th-2 immunopathology, which aggravates infection with SARS-CoV-2. Furthermore, the emerging SARS-CoV-2 strain exhibits several distinct genomic and structural patterns compared to other coronavirus strains, making the development of a suitable vaccine even more difficult. Therefore, the identification of novel small molecule inhibitors (NSMIs) that can interfere with viral entry or viral propagation is of special interest and is vital in managing already infected cases. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, the development of novel inhibitors of ACE2/TMPRSS2 is likely to be beneficial in combating SARS-CoV-2 infections. However, the usage of ACE-2 inhibitors to block the SARS-CoV-2 viral entry requires additional studies as there are conflicting findings and severe health complications reported for these inhibitors in patients. Hence, the current interest is shifted toward the development of NSMIs, which includes natural antiviral phytochemicals and Nrf-2 activators to manage a SARS-CoV-2 infection. It is imperative to investigate the efficacy of existing antiviral phytochemicals and Nrf-2 activators to mitigate the SARS-CoV-2-mediated oxidative stress. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs., (Copyright © 2020 Beeraka, Sadhu, Madhunapantula, Rao Pragada, Svistunov, Nikolenko, Mikhaleva and Aliev.)

Post-traumatic stress disorder (PTSD) is a well-known psychiatric disorder that affects millions of people worldwide. Pharmacodynamic and cognitive-behavioral therapies (CBT) have been used to treat patients with PTSD. However, it remains unclear whether there are concurrent changes in psychopathological and neurophysiological factors associated with PTSD patients. Past reports described those PTSD patients with efficient fatty acid metabolism, neurogenesis, mitochondrial energy balance could improve ability to cope against the conditioned fear responses and traumatic memories. Furthermore, cognitive, behavioral, cellular, and molecular evidence can be combined to create personalized therapies for PTSD sufferers either with or without comorbidities such as depression or memory impairment. Unfortunately, there is still evidence lacking to establish a full understanding of the underlying neurophysiological and psychopathological aspects associated with PTSD. This review has extensively discussed the single nucleotide polymorphism (SNPs) of genetic factors to cause PTSD, the implications of inflammation, neurotransmitter genomics, metabolic alterations, neuroendocrine disturbance (hypothalamus-pituitary-adrenal (HPA) axis), mitochondrial dynamics, neurogenesis, and premature aging related to PTSD-induced psychopathology and neurophysiology. In addition, the review delineated the importance of CBT and several pharmacodynamic therapies to mitigate symptomatology of PTSD.

Cell sheet technology has remained quite popular among tissue engineering techniques over the last several years. Meanwhile, there is an apparent trend in modern scientific research towards combining different approaches and strategies. Accordingly, a large body of work has arisen where cell sheets are used not as separate structures, but in combination with scaffolds as supporting constructions. The aim of this review is to analyze the intersection of these two vast areas of tissue engineering described in the literature mainly within the last five years. Some practical and technical details are emphasized to provide information that can be useful in research design and planning. The first part of the paper describes the general issues concerning the use of combined technology, its advantages and limitations in comparison with those of other tissue engineering approaches. Next, the detailed literature analysis of in vivo studies aimed at the regeneration of different tissues is performed. A significant part of this section concerns bone regeneration. In addition to that, other connective tissue structures, including articular cartilage and fibrocartilage, ligaments and tendons, and some soft tissues are discussed. STATEMENT OF SIGNIFICANCE: This paper describes the intersection of two technologies used in designing of tissue-engineered constructions for regenerative medicine: cell sheets as extracellular matrix-rich structures and supporting scaffolds as essentials in tissue engineering. A large number of reviews are devoted to each of these scientific problems. However, the solution of complex problems of tissue engineering requires an integrated approach that includes both three-dimensional scaffolds and cell sheets. This manuscript serves as a description of advantages and limitations of this method, its use in regeneration of bones, connective tissues and soft tissues and some other details., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

In view of the emerging COVID‑19 pandemic caused by SARS‑CoV‑2 virus, the search for potential protective and therapeutic antiviral strategies is of particular and urgent interest. Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response. Despite the lack of clinical data, certain indications suggest that modulation of zinc status may be beneficial in COVID‑19. In vitro experiments demonstrate that Zn2+ possesses antiviral activity through inhibition of SARS‑CoV RNA polymerase. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore. Indirect evidence also indicates that Zn2+ may decrease the activity of angiotensin‑converting enzyme 2 (ACE2), known to be the receptor for SARS‑CoV‑2. Improved antiviral immunity by zinc may also occur through up‑regulation of interferon α production and increasing its antiviral activity. Zinc possesses anti‑inflammatory activity by inhibiting NF‑κB signaling and modulation of regulatory T‑cell functions that may limit the cytokine storm in COVID‑19. Improved Zn status may also reduce the risk of bacterial co‑infection by improving mucociliary clearance and barrier function of the respiratory epithelium, as well as direct antibacterial effects against S. pneumoniae. Zinc status is also tightly associated with risk factors for severe COVID‑19 including ageing, immune deficiency, obesity, diabetes, and atherosclerosis, since these are known risk groups for zinc deficiency. Therefore, Zn may possess protective effect as preventive and adjuvant therapy of COVID‑19 through reducing inflammation, improvement of mucociliary clearance, prevention of ventilator‑induced lung injury, modulation of antiviral and antibacterial immunity. However, further clinical and experimental studies are required.

Functional diseases of the gastrointestinal tract cause significant damage to the health care system. Their frequent combination in the same patient with the migration of clinical symptoms throughout the digestive tube is accompanied by continuous exacerbations, refractory to the therapy and severe psychosocial disorders. This review provides data on the main etiopathogenetic factors, clinical manifestations, course features and management tactics for patients with overlapping for the most common functional diseases of the gastrointestinal tract.

The levels of the astrocyte markers (GFAP, S100B) were increased unevenly in patients with schizophrenia. Reactive astrogliosis was found in approximately 70% of patients with schizophrenia. The astrocytes play a major role in etiology and pathogenesis of schizophrenia. Astrocytes produce the components that altered in schizophrenia extracellular matrix system which are involved in inflammation, functioning of interneurons, glio-, and neurotransmitter system, especially glutamate system. Astrocytes activate the interneurons through glutamate release and ATP. Decreased expression of astrocyte glutamate transporters was observed in patients with schizophrenia. Astrocytes influence on N-methyl-d-aspartate (NMDA) receptors via D-serine, an agonist of the glycine-binding site of NMDA receptors, and kynurenic acid, an endogenous antagonist. NMDA receptors, on its turn, control the impulses of dopamine neurons. Therefore following theories of schizophrenia are proposed. They are a) activation of astrocytes for neuroinflammation, b) glutamate and dopamine theory, as astrocyte products control the activity of NMDA receptors, which influence on the dopamine neurons., (Copyright © 2020 Tarasov, Svistunov, Chubarev, Sologova, Mukhortova, Levushkin, Somasundaram, Kirkland, Bachurin and Aliev.)

We studied pharmacokinetics and bioavailability of verapamil, propranolol, and ethacizine in healthy volunteers after single oral administration under normal conditions and on the second day of simulated antiorthostatic hypokinesia modeling some effects of microgravity. Under conditions of antiorthostatic hypokinesia, a tendency to a decrease in half-elimination period, mean retention time, and volume of distribution and an increase in the rate of absorption, ratio of maximum concentrations, and relative rate of absorption of verapamil and propranolol were revealed. For ethacizine, a statistically significant increase in the time of attaining maximum concentration and volume of distribution and a decrease in the maximum concentration, rate of absorption, ratio of maximum concentrations, and relative rate of absorption under conditions of antiorthostatic hypokinesia were found.

Cancers of the gastrointestinal tract are widespread among the population and cause significant damage to the health care system. In order to improve the strategy of preventive measures and the detection of oncological diseases at the early stages, it is necessary to provide timely impact on possible risk factors contributing to the onset and progression of malignant neoplasms. This review demonstrates the association between the pathology of the biliary tract and oncological diseases of the digestive system, discusses the possible mechanisms of the influence of cholelithiasis and cholecystectomy on the development of malignant neoplasms of various parts of the gastrointestinal tract.

Objective: Glioblastoma is a highly aggressive and invasive brain and Central Nervous System (CNS) tumor. Current treatment options do not prolong overall survival significantly because the disease is highly prone to relapse. Therefore, research to find new therapies is of paramount importance. It has been discovered that glioblastomas contain a population of cells with stem-like properties and that these cells are may be responsible for tumor recurrence., Methods: A review of relevant papers and clinical trials in the field was conducted. A PubMed search with related keywords was used to gather the data. For example, "glioblastoma stem cells AND WNT signaling" is an example used to find information on clinical trials using the database ClinicalTrials.gov., Results: Cancer stem cell research has several fundamental issues and uncertainties that should be taken into consideration. Theoretically, a number of treatment options that target glioblastoma stem cells are available for patients. However, only a few of them have obtained promising results in clinical trials. Several strategies are still under investigation., Conclusion: The majority of treatments to target cancer stem cells have failed during clinical trials. Taking into account a number of biases in the field and the number of unsuccessful investigations, the application of the cancer stem cells concept is questionable in clinical settings, at least with respect to glioblastoma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: To compare the efficacy of prophylactic administration of mineral-vitamin complexes "Feroglobin-B12" and "Complivit iron" with different degrees of Fe valence., Materials and Methods: 120 female subjects were examined. To determine the quality of life, the SF-36 questionnaire was used. The presence of anxiety was determined on the Spielberger-Khanin Alarm Scale. 30 women with a deficit of Fe were divided into 2 groups of 15 people each. The first group received "Ferroglobin-B12", the second - "Complivit iron" for a month., Results: In a month after the initiation of preventive therapy in women of the 1 group the content of Fe serum was normalized. In the second group, its concentration approached the control values. The difference in Fe content in the 1 and 2 groups was of a reliable nature., Conclusion: The intake of "Ferroglobin-B12" was not accompanied by side effects, and performance indicators, social activity and mental health reached control values, unlike the group of patients taking Complivit iron.

The efficient and rational support of quality om medical care rendering is an important aspect of the system of organization of health care functioning. The study considers the development of concept of patient-oriented model of medical care rendering and also system analysis of main parameters of the model. The study was based on the analysis of publications and normative legislative documents of Minzdrav of Russia and the Federal Foundation of mandatory medical insurance, control boards of health care and territorial Foundations of mandatory medical insurance, subjects of the Russian Federation. The comprehensive analysis resulted in formulation of main parameters and propositions of the patient-oriented model. The concept of related model of organization of medical care rendering to population was presented too. The implementation of the proposed concept in case of its appropriate implementation will favor amelioration of clinical outcomes, increasing of satisfaction and compliance of patients, that will permit to optimize organization of medical care rendering.

The review analyzes the main etiological and pathogenetic mechanisms of the development of NSAID-enteropathy. Particular attention is paid to the role of intestinal microbiota in the manifestation and progression of NSAID-enteropathy. The special role of probiotics in the prevention and treatment of NSAIDs enteropathy is considered.

The review demonstrated results and prospects of non-pharmacological and drug therapy patients with liver disease, not associated with a viral infection. The presented data emphasize the relevance of studying the problem of effective therapy of diseases of the liver and its role in improving the course and outcomes of liver disease.

There is an ongoing search for the molecular and biochemical mechanisms underlying the development of aging and age-associated diseases. At the same time there is growing evidence geroprotective properties of vitamin D.In this review, described in detail the possible mechanisms by which vitamin D affects differentiation, cell proliferation and apoptosis, and describes the potential benefits of this vitamin in the fight against aging and age-related diseases.

Urotensin II (UT II) is an important factor of cellular homeostasis. This regulatory peptide is involved in the pathophysiology of many disorders. For example, it plays an important role in the pathogenesis of acute and chronic diseases, stressful and adaptive reactions of the body, in the development of cardiovascular pathologies, metabolic syndrome, inflammation, liver cirrhosis, renal failure, diabetic nephropathy, reproductive dysfunction, progression of psychosomatic, psychoendocrinal and psychiatric disorders. In this concern, the involvement of UT II in the pathophysiology of many processes determines the perspectives for the development of blockers of urotensin receptors for the treatment of the aforementioned diseases. It is important that even today this kind of perspective is feasible due to the synthesis of a series of GPR14 blockers. The objective of this review is to discuss current molecular mechanisms of biological activity, regulatory functions of UT II, its role in the pathogenesis of different nosologies, as well as analysis of the possible routes of exposure to GPR14 as potential therapeutic targets., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Atrial fibrillation (AF) is one of the most common heart rhythm disorders in the population. Researchers revealed a direct relationship between their incidence and a patient's age long ago. One of the most challenging issues of clinical practice in patients with AF is anticoagulant therapy used in the so-called very elderly patients aged 75 years and older when age itself is a risk factor for developing both thromboembolic and hemorrhagic events due to anticoagulants, regardless of the mechanism of action of the latter. However, scientific data regarding the treatment and prevention of thromboembolic events in elderly and senile patients with AF are very scarce and often uninformative. The data from the EURObservational Research Programme-Atrial Fibrillation Registry Pilot Phase (EORP-AF Pilot) and the randomized clinical studies RELY, ROCKET AF, ARISTOTLE, and AVERROES were analyzed to identify the most safe and most effective anticoagulant for elderly patients (over 75 years). Relying on the analyses of literature data, the authors propose an algorithm based on clinical characteristics for choosing the anticoagulant for patients older than 75 years.

The paper gives an overview of the European Society of Cardiology (ESC) guidelines updated in 2017. The revised and amended guidelines for areas, such as dual antiplatelet therapy (DAT), treatment of patients with ST-segment elevation myocardial infarction (STEMI), and management of patients with valvular heart disease and peripheral artery disease, were presented in late summer of this year. The authors of this paper present an independent analysis and discussion of new data on the key issues of diagnosis and treatment in patients in the above areas. The recommendations on DAT pay special attention to the timing of the therapy and to the choice of its drugs. The updated data on the treatment of patients with STEMI accurately determine the time to percutaneous coronary interventions, approaches to revascularization; the updates touch upon fibrinolytic therapy and new approaches to lipid-lowering therapy too. Recommendations for the management of patients with peripheral artery atherosclerosis propose for the first time a section devoted to the choice of antiplatelet therapy (an antiaggregant and/or an anticoagulant) depending on the clinical situation.

Aim: To evaluate the clinical efficacy of laxatives with different pharmacological effects in the combination therapy in patients with chronic constipation (CC) concurrent with obesity, hypertensive disease, and type 2 diabetes mellitus (DM)., Subjects and Methods: A total of 110 people (45 men, 65 women) aged 45 to 72 years with CC in the presence of concomitant diseases: grade 1 or 2 hypertensive disease + obesity + type 2 DM. The investigators determined the severity of abdominal pain syndrome and flatulence, by indicating the mean frequency of defecations per week and fecal consistency according to the Bristol stool scale; anthropometric parameters; serum biochemistry tests; and serum lipoprotein phenotyping. Quality of life was assessed by the SF-36 questionnaire. The patients were divided into 3 groups according their use of agents: 1) dietary fiber (psyllium); 2) osmotic laxatives (disaccharides); 3) osmotic laxatives (polyethylene glycol)., Results: The patients taking psyllium to treat constipation showed an increasing frequency of defecations and normalization of stool consistency. Incorporating psyllium into combination therapy was accompanied by a significant decrease in the levels of total cholesterol and low-density lipoprotein cholesterol. A similar trend was observed for serum triglycerides. The patients receiving combination therapy including other laxatives displayed no significant differences between lipid metabolic parameters at the beginning and after the end of treatment., Conclusion: The whole complex of properties of psyllium (Mucofalk) can be fully realized in patients with comorbidity and chronic constipation, which is accompanied not only by the normalization of bowel emptying, but also by marked positive changes in the main lipid metabolic parameters and by a reduction in overweight.

The rapid development of medical science and health care practice, the need to improve the quality of health care, the ongoing modernization of education was the basis for scientfic rationale and implementation of the system of continuous medical education, which will be gradually expanded to cover individuals who have undergone 2016 accredited specialist.

Obesity and metabolic syndrome (MS) are risk factors for diabetes, cancer, some cardiovascular and musculoskeletal diseases. Pharmacotherapy should be used when the body mass index (BMI) exceeds 30 kg/m² or 27 kg/m² with comorbidity. Efficacy and safety of pharmacotherapy depend on the mechanism of action of drugs. In this context, drugs affecting the central and peripheral mediator systems such as cannabinoid receptor antagonists (Rimonabant), neuronal reuptake inhibitor of NE and 5 HT (Sibutramine), neuronal reuptake inhibitor of NE 5-HT DA (Tesofensine), agonist of 5 HT 2C receptors (Lorcaserin) have a high risk of side effects on the central nervous and cardiovascular systems when used for a long period. Apparently, the drugs design targeting obesity should screen safer drugs that affect fat absorption (Orlistat), activate energy metabolism (Adipokines), inhibit MetAP2 (Beloranib) and other peripheral metabolic processes. The use of synergies of anti-obesity drugs with different mechanisms of action is an effective approach for developing new combined pharmaceutical compositions (Contrave®, EmpaticTM, Qsymia et al). The purpose of this article is to review the currently available anti-obesity drugs and some new promising trends in development of anti-obesity therapy.