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Introduction In Russia, the prevalence of GERD is 18-46% [Ivashkin V. T., Maev I. V., Trukhmanov A. S., 2011]. GERD leads to a significant decrease in the quality of life of patients, especially with nocturnal symptoms, extraesophageal symptoms (chest pain, persistent cough), and increases the risk of complications such as bleeding from ulcers and erosions, peptic strictures and, which causes the greatest caution, Barrett’s esophagus and esophageal adenocarcinomas Objectives The medical and social significance of the pathology of the thyroid gland and gastrointestinal tract problem is determined by their high prevalence regardless of age, the annual increase in morbidity and the decrease in the quality of life (QOL). Methods Patients were divided in two groups: patients with GERD; patients with GERD and hypothyroidism. Quality of life was studied using the non-specific (general) SF 36 questionnaire. Results The lowest indicators were shown by patients with GERD and hypothyroidism (PF scale - Me 75.00 and 45.00 (p=0.005470), RF scale - 75,00 and 25.00 (p=0.043046), BP scale - 74.00 and 52.00 (p=0.036493), GH scale - 58.00 and 15.00 (p=0.009959)). The second group was more disadvantaged (VT scale - IU 52.50 and 32.50 (p=0.098125), SF scale - 75 00 and 50.00 (p=0.019016), RE scale - 33.30 and 0.00 (p=0.028841), GH scale - 48.00 and 36.00 (p=0.025919). Conclusions According to the results, the presence of combined pathology of the thyroid gland and gastrointestinal tract significantly affected the physical and psychological component of health in the studied patients.

The pathogenesis of metabolic syndrome (MS) is characterized by obesity, hypertension, dyslipidemia and insulin resistance. MS increases the risk of developing type 2 diabetes mellitus (DM2). The neuronal isoform of nitric oxide synthase (nNOS) is defined by complex protein-protein interactions, since nNOS, unlike other isoforms of NOS,contains a C-terminal PDZ domain, which allows it to conjugate with other proteins and, first of all, to interact with an adapter of neuronal, or type 1, nitric oxide synthase (NOS1AP), also denoted CAPON in our work. Changes in the interaction between nNOS and NOS1AP lead to metabolic disorders in brain, heart, liver and skeletal muscles, which plays a key role in the development of MS and T2DM. NOS1AP, interacting with the PDZ domain of nNOS, competes with the postsynaptic density protein (PSD95) and regulates the stability of subcellular localization of nNOS and enzyme expression during synapse formation. NOS1AP promotes nNOS binding to targets such as small GTPase (Dexras1), synapsines, regulating the formation of dendritic roots, mediates activation of the nNOS-p38MAP kinase pathway during excitotoxicity. It has been shown that single-nucleotide polymorphism of the NOS1AP gene and its overexpression in the myocardium leads to the manifestation of long QT syndrome, which is most clearly manifested in elderly patients with DM2. It was found that the genetic polymorphism of NOS1AP affects insulin secretion when using calcium blockers, and can promote the development of DM2. The functional role of NOS1AP in stabilizing the functions of skeletal muscle nNOS in the cytoskeletal complex associated with dystrophin/utrophin was discovered. The purpose of the review is to provide updated information on the role of NOS1AP and the nNOS/NOS1AP complex in the pathogenesis of MS and DM2. The potential molecular mechanisms of the interaction of NOS1AP with nNOS and with other proteins, which leads to change in nNOS activity, localization and content, are discussed.

This literature review presents the role of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO), as well as arginine, the enzyme substrate, in the disease of metabolic syndrome and COVID-19 (SARS-CoV-2 virus). Metabolic syndrome is a combination of obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension. It has been shown that in elderly people, patients with obesity, metabolic syndrome, type 2 diabetes mellitus (DM2), and patients with COVID-19, endothelial dysfunction (ED) and vascular endothelial activation are detected. ED is the main cause of a number of pathological conditions during the development of COVID-19 and earlier in patients with metabolic syndrome, while a sharp drop in the level of nitric oxide (NO) is detected due to a decrease in the expression and activity of eNO synthase and enzyme depletion, which leads to a violation of the integrity of bloodvessels, that is, to vasoconstrictive, inflammatory and thrombotic conditions, followed by ischemia of organs and edema of tissues. It should be noted that metabolic syndrome, DM2, hypertension and obesity, in particular, are age-related diseases, and it is known that blood glucose levels increase with age, which reduces the bioavailability of NO in endothelial cells. Defects in the metabolism of NO cause dysfunction in the pulmonary blood vessels, the level of NO decreases, which leads to impaired lung function and coagulopathy. The review presents possible mechanisms of these disorders associated with ED, the release of eNO synthase, changes in phosphorylation and regulation of enzyme activity, as well as insulin resistance. A modern view of the role of the polymorphism of the eNO synthase gene in the development of these pathologies is presented. To increase the level of endothelial NO, drugs are offered that regulate the bioavailability of NO. These include arginine, agonist NO – minoxidil, steroid hormones, statins, metformin. However, further research and clinical trials are needed to develop treatment strategies that increase NO levels in the endothelium.

The study of the molecular mechanisms of metabolic syndrome (MS) and its complications are among the most acute problems of modern endocrinology. Functional changes in the expression, activity, and regulatory properties of neuronal NO synthase (nNOS), which catalyzes the formation of the most important secondary mediator, nitric oxide (NO), and its dependent NO/cGMP signaling pathways in the brain, myocardium, and skeletal muscles, play a key role among the molecular causes of MS. In the brain, nNOS is associated with NMDA receptors, the hyperactivation of which in MS leads to excessive stimulation of nNOS and hyperproduction of NO, which leads to NO-induced damage to neurons and disruption of the central regulation of physiological processes and neurodegeneration. In the myocardium with MS, there are changes in the expression and localization of nNOS, as well as its functional interaction with cytoskeletal proteins, which leads to disorders of myocardial contraction and hypertrophy. In skeletal muscles, nNOS controls their contraction, oxidative metabolism, is involved in the regulation of vascular relaxation, and also participates in the regulation of glucose transport. A decrease in the expression and activity of nNOS, as well as dysregulation of its activity in MS, cause disturbances of these processes and make a significant contribution to the development of insulin resistance and deterioration of glucose homeostasis. Thus, nNOS can be considered an important therapeutic target in the treatment of MS and other metabolic disorders, as well as to prevent their complications from the nervous and cardiovascular systems and the musculoskeletal system.

Specifically synthesized group of benzimid­azole derivatives possessing varying degrees of delocalization of the positive charge in the cation group of the molecule has been studied in order to search for potential cholinergically active compounds and to study the role of the Coulomb interaction in cholinesterase catalysis. These compounds were reversible inhibitors of cholinesterase (ChE) of human erythrocytes, horse serum, brain of the frog Rana temporaria­ and visual ganglia of the Pacific squid Todarodes pacificus in the presence of acetylthio­choline iodide and propionylthiocholine iodide as substrates. The differences in the nature of reversib­le inhibitory effect were observed. The effect of the inhibitor structure and substrate nature, specific for each of the studied inhibitors, on the character of the process of reversible inhibition was found.

The global risk of viral disease outbreaks emphasizes the need for rapid, accurate, and sensitive detection techniques to speed up diagnostics allowing early intervention. An emerging field of microfluidics also known as the lab-on-a-chip (LOC) or micro total analysis system includes a wide range of diagnostic devices. This review briefly covers both conventional and microfluidics-based techniques for rapid viral detection. We first describe conventional detection methods such as cell culturing, immunofluorescence or enzyme-linked immunosorbent assay (ELISA), or reverse transcription polymerase chain reaction (RT-PCR). These methods often have limited speed, sensitivity, or specificity and are performed with typically bulky equipment. Here, we discuss some of the LOC technologies that can overcome these demerits, highlighting the latest advances in LOC devices for viral disease diagnosis. We also discuss the fabrication of LOC systems to produce devices for performing either individual steps or virus detection in samples with the sample to answer method. The complete system consists of sample preparation, and ELISA and RT-PCR for viral-antibody and nucleic acid detection, respectively. Finally, we formulate our opinions on these areas for the future development of LOC systems for viral diagnostics., 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 Elsevier B.V. All rights reserved.)

A novel membrane-based lateral-flow immunodipstick assay was developed for the fast screening of aflatoxin B(2) (AFB(2)) as a model compound in food samples. The detector reagent consisted of magnetic nanogold microspheres (MnGMs) with nano-Fe(2)O(3) particles as core and gold nanoparticles as shell, and bio-functionalized with monoclonal anti-AFB(2) antibodies. Manually spotted AFB(2)-bovine serum albumin conjugates (AFB(2)-BSA) and goat anti-mouse IgG on nitrocellulose membrane were used as test and control lines, respectively. As the major advantage, experimental results indicated that the visual detection limit (cutoff value) of the MnGM-based dipstick immunoassay with 0.9 ng/ml AFB(2) was about threefold lower compared to a conventional immunodipstick test using gold nanoparticles as detection reagent. Qualitative results (yes/no) could be obtained within 15 min without expensive equipment. The assay was evaluated with AFB(2) spiked or naturally contaminated samples (n=8), including peanuts, hazelnuts, pistacia and almonds, receiving excellent correspondance with results from high performance liquid chromatography (HPLC). Most importantly, the assay gave no false negative results. By controlling the target antibody this assay can be easily extended for use with other food relevant toxins and thus represents a versatile detection method.