Multi-target neural network model of anxiolytic activity of chemical compounds using correlation convolution of multiple docking energy spectra.

Anxiety disorders are one of the most common mental health pathologies in the world. They require searc h and development of novel effective pharmacologically active substances. Thus, the development of new approaches to the search for anxiolytic substances by artificial intelligence methods is an important area of modern bioinformatics and pharmacology.

Dual-Reporter SARS-CoV-2 Replicon for Screening Viral Polymerase Inhibitors.

To design a safe cellular system for testing inhibitors targeting the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, a genetic construct was engineered containing viral cDNA with two blocks of reporter genes while the genes encoding structural S, E, and M proteins were absent. The first reporter block, consisting of Renilla luciferase and green fluorescent protein (Rluc-GFP), was located upstream of the SARS-CoV-2 5'-UTR. Meanwhile, the second block represented by firefly luciferase and red fluorescent protein (Fluc-RFP) was positioned downstream of the transcription regulatory sequence (TRS-N).

[Interventional radiological and endoscopic technologies in diagnosis and treatment of chronic pancreatitis].

This review is devoted to internationally accepted diagnostic algorithms for complicated chronic pancreatitis (CP). In addition, the authors discuss interventional radiological and endoscopic diagnostic and therapeutic procedures, as well as their role in surgical approaches for this disease. Chronic pancreatitis is often diagnosed with severe symptoms following severe course of disease and complications.

[THE ROLE OF POSITION PROFILING IN THE MEDICAL STAFF HIRING].

The personnel shortage in domestic medical organizations continues to be a key problem in healthcare. Modern research in the field of personnel policy reflects a predominantly random choice of specialty by a graduate after graduating from a medical university - 30% of young specialists leave the profession, often noting that the specialty «did not suit». There is a growing need for job profiling in order to more effectively distribute personnel in various sectors of economic activity.

[Regulation of mitophagy and mitochondrial biogenesis by monocarbonyl analogues of curcumin in the cerebral cortex of rats in experimental Alzheimer's disease].

Objective: To evaluate the effect of monocarbonyl analogues of curcumin on changes in the processes of mitophagy and mitochondrial biogenesis in the cerebral cortex of rats with experimental Alzheimer's disease.

Material And Methods: Alzheimer's disease was modeled in Wistar rats of both sexes by injection of β-amyloid fragments into the hippocampus of the animal. Compounds (1E, 4E)-1.

Directed Design, Screening and Antiglycation Activity for 3-Substituted Thiazolium Derivatives, New Analogs of Alagebrium.

Preliminary ab initio calculations led to the synthesis of novel substituted thiazolium salts, analogs of Alagebrium, which were further explored in vitro for their potential as inhibitors of the glycation reaction utilizing three distinct assays: inhibition of fluorescent AGEs formation, anticrosslinking, and deglycation. Despite the unidirectionality of the assays, distinct differences were observed in the mechanisms of interference and activity manifestation by the compounds. The gathered data permitted the formation of hypotheses about the molecular fragments of the studied antiglycators that are of utmost significance in each assay, thereby guiding future design endeavors.

[Stage-by-stage treatment of a patient with severe combined trauma and heart rupture complicated by extensive ischemic stroke].

We demonstrate the peculiarities of diagnosis and successful multi-stage treatment of a patient with severe combined trauma and heart rupture complicated by extensive ischemic stroke in early postoperative period. A patient with severe combined injury was treated at the trauma center grade 3 (State Clinical Hospital No. 25, Volgograd) in 2023.

Takotsubo Syndrome: An International Expert Consensus Report on Practical Challenges and Specific Conditions (Part-2: Specific Entities, Risk Stratification and Challenges After Recovery).

Takotsubo syndrome (TTS) still remains as an enigmatic phenomenon. In particular, long-term challenges (including clinical recurrence and persistent symptoms) and specific entities in the setting of TTS have been the evolving areas of interest. On the other hand, a significant gap still exists regarding the proper risk-stratification of this phenomenon in the short and long terms.

Takotsubo Syndrome: An International Expert Consensus Report on Practical Challenges and Specific Conditions (Part-1: Diagnostic and Therapeutic Challenges).

In the recent years, there has been a burgeoning interest in Takotsubo syndrome (TTS), which is renowned as a specific form of reversible myocardial dysfunction. Despite the extensive literature available on TTS, clinicians still face several practical challenges associated with the diagnosis and management of this phenomenon. This potentially results in the underdiagnosis and improper management of TTS in clinical practice.

[Cytotoxicity Studies of 5-Arylaminouracil Derivatives].

We have previously shown that 5-arylaminouracil derivatives can inhibit HIV-1, herpesviruses, mycobacteria, and other pathogens through various mechanisms. The purpose of this study was to evaluate the potential of 5-arylaminouracils and their derivatives against leukemia, neuroblastoma, and glial brain tumors. 5-Aminouracils with various substituents and their 5'-norcabocyclic and ribo derivatives were screened for cytotoxicity against two neuroblastoma cell lines (SH-SY5Y and IMR-32), K-562 lymphoblastic cells, HL-60 promyeoloblastic cells, and low-passage variants of well-differentiated glioblastoma multiforme (GBM5522 and GBM6138).

A Novel Dipterocarpol Derivative That Targets Alpha-Glucosidase and NLRP3 Inflammasome Activity for Treatment of Diabetes Mellitus.

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia, chronic inflammation, impaired insulin secretion, and/or peripheral insulin resistance. Current α-glucosidase inhibitors approved for clinical use exhibit limited efficacy compared to other glucose-lowering agents. In this study, a series of mono- and bis-benzylidene derivatives were synthesized via aldol condensation of 3-oxo-dammarane triterpenoids with terephthalic aldehyde.

Tocotrienol-rich fraction (TRF) protects against retinal cell apoptosis and preserves visual behavior in rats with streptozotocin-induced diabetic retinopathy.

Background: Tocotrienol is a vitamin E analogue that is known to exert anti-inflammatory and antioxidant effects. Hence, in the current study, the effects of TRF on the expression of pro- and anti-apoptotic proteins in the streptozotocin-induced diabetic rat retinas were investigated. The effect of TRF on the visual behaviour of rats was also studied.

Preclinical Evaluation of Soluble Epoxide Hydrolase Inhibitor AMHDU against Neuropathic Pain.

Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund's adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound (1,1'-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models.

Asymmetric scapuloperoneal phenotype of -related distal myopathy: case series.

Recent research has sparked a discussion on the spectrum of diseases linked to the gene associated with amyotrophic lateral sclerosis and distal myopathy with vocal cord and pharyngeal weakness (VCPDM). To date, fewer than 50 cases of VCPDM have been reported in the literature. We aim to build upon the work of previous researchers by gathering additional information about VCPDM.

Effectiveness of add-on acetazolamide in children with drug-resistant CHD2-related epilepsy and in a zebrafish CHD2 model.

CHD2-related epilepsy is characterized by early-onset photosensitive myoclonic epilepsy with developmental delay and a high rate of pharmacoresistance. We sought to evaluate the efficacy of acetazolamide (ACZ) in CHD2-related epilepsy, due to ACZ's unexpected efficacy in our first patient harboring a pathogenic CHD2 variant. We collected patients from different Eastern European countries with drug-resistant CHD2-related epilepsy who were then treated with ACZ.

Component Composition and Features of Biological Activity of Viscum album (Viscaceae).

The review summarizes the data on the chemical composition and some features of biological activity of the European mistletoe Viscum album L. (Viscaceae Batsch). Among secondary metabolites, viscotoxins, lectins, carbohydrates, amino acids, flavonoids, triterpene acids, and nitrogenous compounds predominate in V.

Assessing the importance and safety of hypoxia conditioning for patients with occupational pulmonary diseases: A recent clinical perspective.

Occupational pulmonary diseases (OPDs) pose a significant global health challenge, contributing to high mortality rates. This review delves into the pathophysiology of hypoxia and the safety of intermittent hypoxic conditioning (IHC) in OPD patients. By examining sources such as PubMed, Relemed, NLM, Scopus, and Google Scholar, the review evaluates the efficacy of IHC in clinical outcomes for OPD patients.

Derivatization of Abietane Acids by Peptide-like Substituents Leads to Submicromolar Cytotoxicity at NCI-60 Panel.

Natural compounds, including diterpenoids, play a critical role in various biological processes and are recognized as valuable components in cancer treatment. Isocyanides multicomponent reactions (IsMCRs) are one of the effective methods to obtain adducts at the carboxyl group with a peptide-like substituent. In this study, dehydroabietic acid and levopimaric acid diene adducts as the starting scaffolds were modified by the multicomponent Passerini (P-3CR) and Ugi (U-4CR) reactions to afford α-acyloxycarboxamides and α-acylaminocarboxamides.

Biomarker profiles associated with reverse ventricular remodelling in patients with heart failure and a reduced ejection fraction: Insights from the echocardiographic substudy of the VICTORIA trial.

Aims: Reverse ventricular remodelling, defined as a decrease in left ventricular end-systolic volume indexed to body surface area (LVESVI) or an increase in left ventricular ejection fraction (LVEF), is associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, the underlying pathophysiological mechanisms remain unclear.

Methods And Results: We evaluated paired core-lab assessed echocardiograms and measurements of 92 biomarkers at baseline and 8 months thereafter in 419 participants with HFrEF.

Efficient synthesis and evaluation of therapeutic potential of fluorine containing 2-arylchromen-4-ones.

A large series of 2-arylchromen-4-ones containing from 1 to 3 fluorine atoms or a trifluoromethyl group in the structure was synthesized by condensation of fluorinated 2-hydroxyacetophenones with benzaldehydes in an alkaline medium and subsequent oxidative cyclization of the resulting 2'-hydroxychalcones by action of I in DMSO. The cytotoxicity of the obtained compounds was studied in glioblastoma cell line, SNB19, and in a monkey-derived normal kidney epithelium cell line, Vero. In addition, antiglycation activity of the obtained compounds was evaluated.

Antiplatelet and Antithrombotic Properties of Compound L-36, a 6H-1,3,4-Thiadiazine Derivative.

Compound L-36, a new derivative of 6H-1,3,4-thiadiazine, was studied in in vitro and in vivo experiments. This compound exhibits high antiplatelet and antithrombogenic activity. In in vitro experiments, compound L-36 by its antiplatelet activity (by IC) was superior to acetylsalicylic acid by 9.