Endogenous multiple modified LDL (mLDL) and the renin-angiotensin system play a significant role in the development of atherosclerosis. It has been found that by behavioral and hemodynamic parameters the physiological activity of angiotensin II (Ang II) in combination with mLDL is considerably modified due to weakening of its diuretic effect and the inversion of hypertensive and tachyarrhythmic effects. Atherosclerosis is a long-term pathological process, so a single administration of artificially synthesized Ang I-mLDL complexes can be considered a model of the first contact of the body with pathogenic factors. We believe that angiotensin complexes with mLDL participate in adaptive and compensatory mechanisms at the initial stages of atherosclerosis and later contribute to its progression.

We have previously demonstrated multidirectional changes in trypsin activity and some serum biochemical parameters in rats under conditions of water and food deprivation with following satiation. In the present study, administration of soybean trypsin inhibitor (STI) to animals subjected to water and food deprivation caused a moderate decrease in trypsin activity and an increase in the serum concentration of total protein, which attested to deceleration of protein metabolism. Significant changes in the content of cholesterol and triglycerides against the background of STI administration were also found indicating intensification of lipid and energy metabolism. These findings suggest that STI prevents disturbances of metabolic processes in the body under conditions of water and food deprivation. However, the peculiarities of STI influence on metabolic processes require further study.

Citation: Kuzmina IV, Tolpygo SM, Kotov AV, Shoibonov BB and Zamolodchikova TS (2024) Basal pancreatic secretion in a comparative aspect in poultry and rodents. Front. Physiol. 15:1340130. doi: 10.3389/fphys.2024.1340130

OPINION article Front. Endocrinol., 23 January 2024Sec. Diabetes: Molecular Mechanisms Volume 15 - 2024 | https://doi.org/10.3389/fendo.2024.1293221

Irina V. Kuzmina*Svetlana M. TolpygoAlexander V. KotovBatogab B. ShoibonovTatyana S. ZamolodchikovaNatalya V. Ovchinnikova

Trypsin is mainly regarded as a digestive enzyme, but there is evidence that activation of protease-activated receptor-2 (PAR-2) leads to behavioral changes. There are no data on trypsin activity in the serum of animals under conditions of thirst and starvation in the available literature. In our experiments, water deprivation led to a significant (p⩽0.05) increase in trypsin activity in rats, and food deprivation led to its decrease in comparison with controls (free access to water and food). After deprived rats received water and food, a decrease in trypsin activity was observed in both experimental groups. Changes in trypsin activity under conditions of water or food deprivation and after satiation were accompanied by shifts in some biochemical parameters of the bloods. Under conditions of metabolic stress (starvation and thirst), opposite changes in trypsin activity seem to indicate its participation in the mechanisms of adequate restructuring of metabolism and maintenance of vital processes in the body.

The research task has been testing of the method of modified low density lipoproteins (mLDLP) determina- tion as the chronic inflammatory process marker in poultry and laboratory mammals (rats and mice) serum. Experiments have been carried out with 3 days chicks and 180 days layers and also with laboratory rat males from Wistar population and laboratory mice males from C57BI/6 line. Serum investigation results have shown that poultry had increased mLDLP content in 3 and 180 days age. It means that mLDLP determination in poultry at different ontogenesis stages will give the possibility to identify metabolic process disruption timely and to carry out necessary treatment and preventive measures and to correct poultry feeding and management at different raising periods. Determination of mLDLP levels in laboratory mammals will give the possibility to form personalized animal groups for researches with normal and increased mLDLP lev- els for the results reliability increasing.

Serine proteases, including trypsin, thrombin, plasminogen activators, plasmin and several others, are synthesized in nervous tissue, mainly in the brain, including the cortex, limbic system and cerebellum. This review examines the involvement of serine proteases in neuroplasticity and behavioral regulation. Endogenous serine proteases play an important role in the formation, development and maintenance of the nervous system. Through limited proteolysis, these proteases activate PARs (protease-activated receptors), modify other receptors or their ligands, process neurotrophic factors, degrade intercellular matrix and cell adhesion proteins and initiate complex signal transduction cascades necessary for structural modification of synapses. The involvement of serine proteases in morphological and functional synaptic plasticity may underlie cognitive processes, including learning and memory in animals and humans.

The starting point of this paper is the conceptual framework of Oparin-Kolmogorov-Anokhin on the constructive role of sensory variability mechanisms in various forms of life and processes of various structural and functional complexity occurring in them. The paper attempts to highlight the potential of studying the psychophysiological and neurobiological consequences of sensory variability using non-traditional models of formal neurons based on the ranking of input perturbations to compute the output reaction. This required the simplest non-numbering procedure of 'weighing on lever scales' and permutation-substitution operations implemented in prebiological, biological and supbiological environments, as well as processes occurring in them. The paper proposes promising areas of research in the development and practical use of biohybrid technologies.

The modern period of medicinal and pharmacologic development is characterized by significant achievements in the area of peptide-based drugs. The concept of peptide regulation of organism biological functions detected feasibility for the development of new highly efficient regulatory peptide-based drugs that has resulted in heavy growth of pharmacologic studies in the area of peptide drugs, including the agonists of receptors associated with G proteins (GPCR) (Wacker et al., 2017; Grieco and GomezMonterrey, 2019). The use of peptides as drugs is limited due to their short half-life, rapid degradation, and high clearance, but in some cases, for example, for Giapreza, containing angiotensin II (AngII), a short plasma half-life may be clinically beneficial (Khalique and Ferguson, 2019). In order to improve pharmacologic properties of the peptide drugs, a special strategy of peptide conjugation with high molecular weight compounds, including proteins, is developed (Bumbaca et al., 2019; Davenport et al., 2020). A similar approach is used to create conjugate peptide vaccines for stabilization, delivery to the immune competent cells, and stimulation of the immune reaction; the target peptide antigen is conjugated with any protein, such as keyhole limpet hemocyanin or bovine serum albumin (BSA). An analogous method for vaccine creation is proposed for the prospective method of hypertension immune treatment: peptide–protein antihypertensive vaccines contain different factors of the renin–angiotensin system (RAS), including protein-conjugated angiotensins (Downham et al., 2003; GarayGutiérrez et al., 2021). In pursuit of the goal of correcting pathologic conditions using synthetic peptide–protein preparations, it should be borne in mind that the incorporation of a peptide into an artificial macromolecular construct is inevitably accompanied with changes in its structural conformation characteristics due to new peptide–protein interactions. For this reason, the peptide hormone integrated into the peptide–protein complex is an altered ligand with globally modified signaling properties. There are cases when the use of GPCRtargeted peptide drugs leads to unexpected reactions and dangerous side effects (Allen and Roth, 2011). Based on literature and own data, we show by the example of angiotensins–multifunctional factors of the RAS that the hormones included into the synthetic peptide–protein complexes could globally change their properties till reverse agonism and cause unpredictable physiological effects. Edited by: Salvatore Salomone, University of Catania, Italy

OPINION article Front. Immunol., 03 March 2020Sec. Nutritional Immunology Volume 11 - 2020 | https://doi.org/10.3389/fimmu.2020.00411

Актуальность. Определение фибриногена (ФГ) по Клауссу является чувствительным к гипо-, дис- и гипер-фибриногенемии, а также к продуктам деградации фибрина, которые влияют на процесс коагуляции и могут быть причиной занижения или повышения уровня фибриногена. Цель настоящей работы - разработка простого турбидиметрического теста для определения фибриногена и оценка его функциональности. Материалы и методы. В работе определяли фибриноген в цитратных плазмах 96 пациентов по методу Клаусса, модифицированным методом Рутберга и новым турбидиметрическим тестом. Результат. Разработан простой турбидиметрический тест определения фибриногена, основанный на определении коагулированного фибриногена при рекальцификации цитратной плазмы по формуле: ФГ (г / л) = ΔА450 × 5,12, где ΔА450 - изменение оптической плотности в опытной пробе; 5,12 - переводной коэффициент ΔА450 в г/л ФГ. Корреляционный анализ показал высокую степень сходимости результатов (R = 0,843). При разнице ФГ более 10% по Клауссу и по разработанному методу констатируют как нарушенную функциональность ФГ. Заключение. Использование простого, доступного турбидиметрического метода определения фибриногена в рутинных исследованиях позволяет оценивать функциональность фибриногена. Background. The Clauss fibrinogen assay is sensitive to hypo-, dys- and hyper-fibrinogenemia, as well as to fibrin degradation products, which may affect coagulation and cause underestimation of or increase the fibrinogen level. The aim of this study was to develop a simple turbidimetric test to measure fibrinogen and evaluate its functionality. Materials and methods. In this study, fibrinogen was measured in citrate plasma from 96 patients using the Clauss assay, a modified Rutberg method, and a new turbidimetric test. Result. A simple turbidimetric test was developed for measuring fibrinogen. This test is based on measuring coagulated fibrinogen during recalcification of citrate plasma according to the formula, FG (g/l) = ΔА450 × 5.12, where ΔА450 is a change in optical density of the experimental sample; 5.12 is a conversion coefficient ΔА450 in g/l FG. Correlation analysis showed a high degree of agreement between the results (R = 0.843). With a FG difference of more than 10% by the Clauss assay and the developed method, impaired functionality of the FG is stated. Conclusion. Using a simple, affordable turbidimetric method to determine fibrinogen in routine studies allows accessing the fibrinogen functionality.

Разработан скрининг-тест для определения множественно-модифицированных липопротеинов низкой плотности (ммЛПНП) в сыворотке крови для рутинных исследований. Инкубация сыворотки в буфере, содержащем 9,1% поливинилпирролидона 35000 (ПВП-35) приводит к полной агрегации ммЛПНП. Патогенность выделенных ммЛПНП подтверждена в тестах связывания системы комплемента и литической активности in vitro , а также в тесте сосудистой дистонии у крыс in vivo . Предлагаемый способ отличается высокой производительностью и низкой себестоимостью. Метод включает 2 операции - смешивание сыворотки с раствором 10% ПВП-35 в 96-луночных иммунологических планшетах, инкубация в течение 10 мин при комнатной температуре и турбидиметрия при 450 нм на ИФА-ридере. Проведены исследования взаимосвязи концентрации ммЛПНП в сыворотке крови и толщины комплекса интима-медиа по данным ультразвукового дуплексного сканирования сонных артерий у 78 человек с низким сердечно-сосудистым (SCORE <1%) и низким кардио-метаболическим рисками (CMDS 0-1). Из всех фракций липидного спектра крови ммЛПНП показали самый высокий коэффициент корреляции с показателями субклинического атеросклероза, что подтверждает высокий атерогенный потенциал ммЛПНП. A screening test was developed to determine multiply-modified low-density lipoprotein (mmLDL) in serum for routine studies. Incubation of serum in a buffer containing 9.1% polyvinylpyrrolidone 35,000 (PVP-35) results in complete aggregation of mmLDL. Pathogenicity of isolated mmLDL was confirmed during binding tests of the complement system and lytic activity in vitro , and also in vascular dystonia test with rats in vivo . The proposed method is characterized by high productivity, low cost, includes 2 operations - mixing serum with a solution of 10% PVP-35 in 96-well immunoassay plates, incubating for 10 min at room temperature and turbidimetry at 450 nm on an ELISA reader. A study was made to determine relationship between concentration of mmLDL in the blood serum and thickness of the intima-media complex from data of ultrasound duplex scanning of carotid arteries with 78 people with low cardiovascular risk (SCORE <1%) and low cardiovascular risk (CMDS 0-1). Of all fractions of the lipid spectrum of the blood, mmLDL showed the highest correlation coefficient with the indices of subclinical atherosclerosis, which confirms high atherogenic potential of mmLDL.

A screening test was developed to determine multiply-modified low-density lipoprotein (mmLDL) in serum for routine studies. Incubation of serum in a buffer containing 9.1% polyvinylpyrrolidone 35,000 (PVP-35) results in complete aggregation of mmLDL. Pathogenicity of isolated mmLDL was confirmed during binding tests of the complement system and lytic activity in vitro, and also in vascular dystonia test with rats in vivo. The proposed method is characterized by high productivity, low cost, includes 2 operations — mixing serum with a solution of 10% PVP-35 in 96-well immunoassay plates, incubating for 10 min at room temperature and turbidimetry at 450 nm on an ELISA reader. A study was made to determine relationship between concentration of mmLDL in the blood serum and thickness of the intima-media complex from data of ultrasound duplex scanning of carotid arteries with 78 people with low cardiovascular risk (SCORE

Цель настоящей работы - разработка доступного теста для скрининга функциональной активности системы комплемента по классическому пути. Материалы и методы. В работе исследовали сыворотки крови 90 относительно здоровых лиц с избыточной массой тела (ИМТ >25) без метаболического синдрома. Иммуноферментный анализ функциональной активности системы комплемента по классическому пути проводили с использованием коммерческого набора. Реакцию лизиса эритроцитов барана, сенсибилизированных антителами (ЕА), оценивали турбидиметрически по снижению оптической плотности суспензии при длине волны 620 нм, степень лизиса определяли по калибровочному графику. Результаты. Разработан простой скрининг-тест для определения функциональной активности классического пути системы комплемента. Корреляционный анализ показал высокую степень сходимости результатов (r = 0,496), полученных разными методами. Заключение. Скрининг-тест для определения функциональной активности классического пути системы комплемента является быстрым, информативным и доступным для рутинных исследований. The aim of this work was to develop an accessible test for screening the functional activity of the complement system classic pathway. Materials and methods. Blood serum from 90 relatively healthy, overweight (BMI>25) individuals without the metabolic syndrome was studied. Enzyme immunoassay of the complement system functional activity following the classic pathway was performed using a commercial kit. The lysis of antibody-sensitized sheep erythrocytes was evaluated turbidimetrically by a decrease in suspension optical density at a wavelength of 620 nm; the lysis intensity was determined by the calibration curve. Results. A simple screening test was developed to determine the functional activity of the complement classic pathway. A high degree of correlation (r = 0.496) was observed between results obtained by different methods. This screening test for evaluating the functional activity of classic complement system pathway is fast, informative, and available for routine research.

Aim of the study. Determination of the potential opportunity of immune protease cathepsin G (Cat G) to participate in the regulation of homeostasis and protective reactions in the intestinal epithelium by interacting with cell adhesion proteins (cadherins). Materials and methods. Biopsies of the human duodenal mucosa were examined by confocal immunofluorescence microscopy using specific antibodies to desmogleins 1-3 (DSGs 1-3), E-cadherin and Cat G of human. Results. The presence of DSG 2 in the contact area of the basolateral membrane of epitheliocytes of intestinal villi and intestinal glands (crypts) with the basal membrane was demonstrated. DSGs 1 and 3 were not detected in the test samples. E-cadherin is located in the zone of the basolateral membrane of enterocytes, goblet cells and Paneth cells. E-cadherin-specific fluorescence is also found between the secretory granules of Paneth cells, which indicates the synthesis of this protein by Paneth cells and/or E-cadherin role in intracellular signaling. In inflammation (duodenitis II-III degree) Cat G-containing granules are localized near the basal membrane of villi and intestinal glands. Conclusions. The catalytic properties of Cat G and its close proximity to the cell adhesion proteins (DSG 2 and E-cadherin) indicate the possibility of interaction of these proteins and their role in the regulation of tissue metabolism, modification and maintenance of the barrier properties of the epithelium during the development of protective and / or pathological processes.

The renin-angiotensin system (RAS) is the universal multiple-factor regulator of many vital processes at the organismal, tissue and cellular levels. Classical (circulating) RAS provides maintenance of arterial pressure, a water and salt balance, lipid and glucose homeostasis. Local tissue RAS are functioning independently and participating in metabolic processes and protective reactions. Local RAS of a small intestine mucosa is presented practically by a complete rangeof the components (renin, angiotensinogen, angiotensin-converting enzymes, angiotensin receptors) localized, mainly, in an intestinal epithehum, lamina propria and muscularis mucosa. Local RAS participates in regulation of the most levels of activity ofa small intestine, influencing on an intestinal motility, secretory-transport processes, adaptation and protective reactions. The experimental data presented in this review are very promising for the detection of possible complications when using drugs that alter the activity of the RAS-related unexplored effects of the interaction of these drugs with their potential targets, localized not only in the blood vessels, but also directly to the niucosa of the gastrointestinal tract. This is especially important in connection with the extensive use of drugs that modulate the activity of the RAS in the practice of the treatment of cardiovascular diseases such as hypertension, atherosclerosis, endothelial dysfunction, and others.

In rats with acute hypo- and hyperglycemia the initial effects of free angiotensin IV and its complexes with functionally different carrier proteins (transport protein BSA, neuron-specific protein S100b) on hemodynamics and behavior of rats were qualitatively altered, in comparison with those in intact animals. At the same time, free angiotensin IV under conditions of hypo- and hyperglycemia paradoxically acquired functions of angiotensin II (moderate hypertension, tachycardia, polydipsia and activation of instrumental drinking behavior). Concurrently, complexes of angiotensin IV with BSA and S100b acquired functions of free angiotensin IV (hypotensia, suppression of drinking behavior). It is suggested that complexes of angiotensin IV with functionally different proteins are involved in a differentiated way first in compensation of behavior and hemodynamics impairment produced by acute and/or chronic hypo- and hyperglycemia, and then in qualitative transformation of these adaptive processes into stable pathological condition involving mechanisms of so called “metabolic memory”.