New Organometallic Ru(II) Compounds with Lonidamine Motif as Antitumor Agents.

The combination of one molecule of organic and metal-based fragments that exhibit antitumor activity is a modern approach in the search for new promising drugs. In this work, biologically active ligands based on lonidamine (a selective inhibitor of aerobic glycolysis used in clinical practice) were introduced into the structure of an antitumor organometallic ruthenium scaffold. Resistant to ligand exchange reactions, compounds were prepared by replacing labile ligands with stable ones.

Consensus Ensemble Multitarget Neural Network Model of Anxiolytic Activity of Chemical Compounds and Its Use for Multitarget Pharmacophore Design.

A classification consensus ensemble multitarget neural network model of the dependence of the anxiolytic activity of chemical compounds on the energy of their docking in 17 biotargets was developed. The training set included compounds thathadalready been tested for anxiolytic activity and were structurally similar to the 15 studied nitrogen-containing heterocyclic chemotypes. Seventeen biotargets relevant to anxiolytic activity were selected, taking into account the possible effect on them of the derivatives of these chemotypes.

The role of iNOS inhibition in the mechanism of the cardioprotective effect of new GABA and glutamic acid derivatives in the model of acute alcoholic myocardial injury in rats.

The cardioprotective effects of new derivatives of glutamic acid (glufimet) and GABA (mefargin) were studied in rats exposed to acute alcohol intoxication (AAI) under conditions of selective blockade of inducible NO-synthase (iNOS). AAI induced a pronounced decrease in the contractile function of the myocardium during exercise tests (load by volume, test for adrenoreactivity, isometric exercise), caused mitochondrial dysfunction and increased processes of lipid peroxidation (LPO) in heart cells. A decrease in NO production during iNOS inhibition and AAI improved the respiratory function of mitochondria, a decreased the level of LPO products, and increased mitochondrial superoxide dismutase activity of heart cells.

Solid herbal extract of L. improves morphofunctional condition of rats' myocardium in chronic alcohol intoxication.

Background And Aim: Chronic alcohol intoxication (CAI) induces heart damage. One of the promising ways of its treatment involves the administration of herbal medicinal products. The purpose of this study was to explore the effect of solid herbal extract of Primula veris L.

3-Arylidene-2-oxindoles as GSK3β inhibitors and anti-thrombotic agents.

Development of novel agents that prevent thrombotic events is an urgent task considering increasing incidence of cardiovascular diseases and coagulopathies that accompany cancer and COVID-19. Enzymatic assay identified novel GSK3β inhibitors in a series of 3-arylidene-2-oxindole derivatives. Considering the putative role of GSK3β in platelet activation, the most active compounds were evaluated for antiplatelet activity and antithrombotic activity.

Long term results of non-refluxing ureteral reimplantation in the pediatric population.

Purpose: To evaluate the long-term results of UR and to determine the difference between patients with VUR and OMU in terms of re-obstruction rate, complications associated with pregnancy, and de novo reflux.

Methods: Two-site retrospective study with 69 patients (36 females and 33 males) with a mean age of 5 ± 3.4 years.

Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy.

Aim: Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF.

[Study of the effect of Unifuzol on cognitive impairment and damage to the hippocampus and cerebral cortex during course administration to rats with bilateral stenosis of the common carotid arteries, causing chronic circulatory failure].

Objective: To study the effect of Unifuzol (L-arginine sodium succinate) on cognitive impairment, cerebral blood flow, and damage to the tissues of the hippocampus and cerebral cortex during a 10-day course of administration to rats with chronic cerebral ischemia (CCI) caused by bilateral stenosis of the common carotid arteries (CCA).

Material And Methods: The study was conducted on male rats with CCI caused by bilateral stenosis of the CCA by 60%. 40 days after surgery, rats received Unifusol (21, 42 and 84 ml/kg), nicergoline (10 mg/kg), citicoline (500 mg/kg) or placebo (0.

Screening of Lesser-Known Salted-Dried Fish Species for Fatty Acids, Tocols, and Squalene.

The fillets and roes of 29 species of dry-salted fishes consumed in Eurasian countries were analyzed for fatty acids (FAs), tocols, and squalene, looking for derived health benefits. FAs were analyzed by GC-FID, and tocols and squalene were analyzed by HPLC-DAD. With some exceptions, docosahexaenoic (DHA, 22:6-3), eicosapentaenoic (EPA, 20:5-3), and arachidonic (ARA, 20:4-6) acids were the prominent polyunsaturated fatty acids (PUFAs).

Comparability of biosimilar romiplostim with originator: Protein characterization, animal pharmacodynamics and pharmacokinetics.

The results of preclinical studies of romiplostim analogue GP40141 are presented. The effect of a cell proliferation, phosphorylation of the TPO receptor and JAK2 phosphorylation were studied in the presence of romiplostim and in the presence of GP40141 in a cell line of mice (Mus musculus) lymphoblasts with stable expression of human TPO receptor 32D-hTPOR clone 63. Binding to the TPO receptor and to the neonatal Fc receptor (FcRn) was examined for both romiplostim and the developed analogue.

Neuroprotection by trans-resveratrol in rats with N-methyl-D-aspartate (NMDA)-induced retinal injury: Insights into the role of adenosine A1 receptors.

Adenosine A1 receptors (AA1R) have been shown to counteract N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitotoxicity. In the present study, we investigated the role of AA1R in neuroprotection by trans-resveratrol (TR) against NMDA-induced retinal injury. In total, 48 rats were divided into the following four groups: normal rats pretreated with vehicle; rats that received NMDA (NMDA group); rats that received NMDA after pretreatment with TR; and rats that received NMDA after pretreatment with TR and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an AA1R antagonist.

Synthesis of 1-[ω-(Bromophenoxy)alkyl]-3-Naphthalenylmethyl Uracil Derivatives and Their Analogues as Probable Inhibitors of Human Cytomegalovirus Replication.

A new series of 1-[ω-(bromophenoxy)alkyl]-uracil derivatives containing naphthalen-1-yl, naphthalen-2-yl, 1-bromonaphthalen-2-ylmethyl, benzyl, and anthracene-9-ylmethyl fragments in position 3 of uracil residue was synthesized. The antiviral properties of the synthesized compounds against human cytomegalovirus were studied. It was found that the compound containing a bridge consisting of five methylene groups exhibits a high anti-cytomegalovirus activity in vitro.

3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors.

The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2.

[Laparoscopic versus laparoscopy-assisted suturing of perforated peptic ulcers (meta-analysis)].

Objective: To compare laparoscopic and laparoscopy-assisted repair of perforated peptic ulcer using evidence-based methods.

Material And Methods: A systematic review and meta-analysis were carried out in accordance with the recommendations of the Ministry of Health of Russian Federation and

Unlabelled: Data searching was carried out in Russian and English languages using the E-library, Cochrane Library and PubMed databases. We analyzed titles and references in specialized journals and thematic reviews, respectively.

Derivatives of 2-aminobenzimidazole potentiate ASIC open state with slow kinetics of activation and desensitization.

The pharmacology of acid-sensitive ion channels (ASICs) is diverse, but potent and selective modulators, for instance for ASIC2a, are still lacking. In the present work we studied the effect of five 2-aminobenzimidazole derivatives on native ASICs in rat brain neurons and recombinant receptors expressed in CHO cells using the whole-cell patch clamp method. 2-aminobenzimidazole selectively potentiated ASIC3.

[The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries].

Background: There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI).

Aim: To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period.

Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury.

The problem of lung damage originating from excessive inflammation and cytokine release during various types of infections remains relevant and stimulates the search for highly effective and safe drugs. The biological activity of the latter may be associated with the regulation of hyperactivation of certain immune cells and enzymes. Here, we propose the design and synthesis of amino derivatives of 4,6- and 5,7-diaryl substituted pyrimidines and [1,2,4]triazolo[1,5-]pyrimidines as promising double-acting pharmacophores inhibiting IL-6 and NO.

[Анализ влияния коморбидной сердечно-сосудистой патологии на течение и исходы COVID-19 у госпитализированных пациентов в первую и вторую волну пандемии в Евразийском регионе].

Цель:  Изучение особенностей клинического течения новой коронавирусной инфекции и  влияния сопутствующих заболеваний на исход заболевания у госпитализированных больных с инфекцией SARS-CoV-2 в первую и вторую волны пандемии.Методы и результаты.  Для оценки особенностей течения COVID-19 в Евразийском регионе были созданы международные регистры АКТИВ 1 и во время второй волны пандемии АКТИВ 2.

Plant-food-derived Bioactives in Managing Hypertension: From Current Findings to Upcoming Effective Pharmacotherapies.

A sedentary lifestyle has evoked a high risk of cardiovascular (CV) disease, diabetes, and obesity, all of them with high morbimortality rates and with a common denominator, hypertension. Numerous pharmacological drugs have been used for the treatment of hypertension. However, the side effects associated with the use of existing pharmacological therapies have triggered a demand for plant-based medications.

A comparative analysis of lecturers' satisfaction with Anatomage and Pirogov virtual dissection tables during clinical and topographic anatomy courses in Russian universities.

Anatomy is increasingly taught using computer-assisted learning tools, including electronic interactive anatomy dissection tables. Anatomage was he first virtual anatomy dissection table introduced in Russian medical universities and gained popularity among lecturers and students. The Pirogov interactive anatomy table was recently released, but the strengths and weakness of each platform is currently unknown.

6-(Tetrazol-5-yl)-7-aminoazolo[1,5-]pyrimidines as Novel Potent CK2 Inhibitors.

In this work, we describe the design, synthesis, and structure-activity relationship of 6-(tetrazol-5-yl)-7-aminoazolo[1,5-a]pyrimidines as inhibitors of Casein kinase 2 (CK2). At first, we optimized the reaction conditions for the azide-nitrile cycloaddition in the series of 6-cyano-7-aminoazolopyridimines and sodium azide. The regioselectivity of this process has been shown, as the cyano group of the pyrimidine cycle was converted to tetrazole while the nitrile of the azole fragment did not react.

Caucasian Blueberry: Comparative Study of Phenolic Compounds and Neuroprotective and Antioxidant Potential of Vaccinium myrtillus and Vaccinium arctostaphylos Leaves.

(1) Background: Two Caucasian blueberries L. and L. are famous berry bushes growing in the Caucasus region and used to treat neurological diseases, but the chemistry and bioactivity of leaf extracts are still poorly studied.

Discovery and evaluation of biphenyl derivatives of 2-iminobenzimidazoles as prototype dual PTP1B inhibitors and AMPK activators with in vivo antidiabetic activity.

This work describes the synthesis of series hydrobromides of N-(4-biphenyl)methyl-N'-dialkylaminoethyl-2-iminobenzimidazoles, which, due to the presence of two privileged structural fragments (benzimidazole and biphenyl moieties), can be considered as bi-privileged structures. Compound 7a proved to activate AMP-activated kinase (AMPK) and simultaneously inhibit protein tyrosine phosphatase 1B (PTP1B) with similar potency. This renders it an interesting prototype of potential antidiabetic agents with a dual-target mechanism of action.

[Antiastenic effect of sequential levocarnitine and acetylcarnitine therapy in patients with cardiovascular diseases].

Objective: Evaluation of the antiasthenic effect of sequential therapy with levocarnitine (LC) and acetylcarnitine (ALC) in patients with arterial hypertension and/or ischemic heart disease (CHD) with asthenic syndrome (AS).

Material And Methods: An open comparative study included 120 patients aged 54-67 years in patients with arterial hypertension and/or coronary artery disease with AS. Patients of group1 (=60), in addition to basic therapy for the underlying disease, received LC (Elcar solution for intravenous and intramuscular injection of 100 mg/ml, the company PIQ-PHARMA) intravenously for 10 days at a dose of 1000 mg/day, followed by a transition to oral administration of ALC (Carnicetine, the company PIQ-PHARMA) 500 mg (2 capsules) 2 times a day for 2 months.

Impact of heart failure on all-cause mortality in COVID-19: findings from the Eurasian International Registry.

Aims: To study all-cause mortality in patients hospitalized with COVID-19 with or without chronic heart failure (CHF) during hospitalization and at 3 and 6 months of follow-up.

Methods And Results: The international registry Analysis of Comorbid Disease Dynamics in Patients with SARS-CoV-2 Infection (ACTIV) was conducted at 26 centres in seven countries: Armenia, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russian Federation, and Uzbekistan. The primary endpoints were in-hospital all-cause mortality and all-cause mortality at 3 and 6 months of follow-up.