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In this study, the fungus strain LS-4.2 isolated from the bottom sediments of Lake Lower Suzdalskoe was tested for its algicidal activity. We identified the strain LS-4.2 as Penicillium canescens summing its morphological characteristics with the reported DNA sequence. We revealed that the filtrate of a 7-day culture of the fungus suppressed the cell growth of toxic Microcystis aeruginosa. Our results showed that the filtrate caused rapid M. aeruginosa growth inhibition up to complete cell lysis recorded after 4 days. Living fungal mycelia did not suppress the growth of cyanobacterium. According to the results of this study we suppose that strain LS-4.2 may be a potential bioagent in the control of cyanobacterial blooms.

Innovative modernization of Russia’s dairy industry is a key factor in ensuring the country’s food and environmental security in the context of increasing export orientation. The goal of our research is to substantiate the concept for development of the dairy industry in Russia and to develop forecast scenarios for its functioning based on the introduction of the best available technologies. The paper reveals specific features of functioning of the industry and the contradictions they cause. We conclude that effective development of the industry is possible only under balanced state policy that takes into account international experience and the challenges that the industry has to deal with. We analyze the use of the best available technologies in the dairy industry in Russia and propose a model for development of the concept of the dairy industry on the basis of the best available technologies. Our scenarios for development of Russia’s dairy industry are of practical interest, as well as our conclusion that the state policy for the development of this industry should be based on an innovative scenario involving its system modernization, which will help ensure food and environmental security of the country and promote dairy products exports. We note that the development and implementation of the best available technologies at enterprises of the dairy industry with the use of foreign experience and tools of state regulation can serve as a response to the system-wide and rapid transformations that are taking place in the industry at the present time. The material of the paper can be used in the educational process in universities; it is relevant for managers and specialists of the dairy industry and for scientists involved in its development through the use of the best available technologies

The article discusses the importance of an individual approach when considering the time needed for learning basic technical courses of a technical University (such as higher mathematics, physics, etc.) to motivate a student to obtain 100% standard of mastering the educational material using the experience of the Department of mathematics. In the modern conditions of the world of information technologies it is extremely important to teach people how to handle information independently and, what is the most important, to assess it. As you know, universities set a certain studying time for each academic subject fixed by curriculum. But time should not be a constant component. Obviously, such a new approach will require innovation in the methodological literature. Using the experience of the Department of Mathematics of MGSU the author offers methodical developments and research works for studying under the direction of a teacher along with standard digestion of the curriculum.

Abstract Background Accumulating evidences suggest that Hsp 70, the inducible component of Hsp70 family, might release from a living cell. Here we show that a pharmacological inhibitor of phospholipase C activity U73122 caused a 2–4 fold reduction of an intracellular level of Hsp70 in A431 human carcinoma cells. Results A depletion of Hsp70 under U73122 was a result of the protein release since it was detected in cell culture medium, as was established by immunoprecipitation and precipitation with ATP-agarose. The reduction of Hsp70 level was specifically attributed to the inhibition of PLC, since the non-active inhibitor, U73343, had no effect on Hsp70 level. The PLC-dependent decrease of Hsp70 intracellular level was accompanied by the enhanced sensitivity of A431 cells to the apoptogenic effect of hydrogen peroxide. Here for the first time we demonstrated one of the possibilities for a cell to export Hsp70 in PLC-dependent manner. Conclusion From our data we suggest that phospholipase C inhibition is one of the possible mechanisms of Hsp70 release from cells.

Astrocytes are subtypes of glial cells involved in metabolic, structural, homeostatic, and neuroprotective processes that help neurons maintain viability. Insulin-like growth factors IGF-1 and IGF-2 are known to have neuroprotective effects on neurons and glial cells through interaction with specific receptors. IGF forms a complex with IGF-binding proteins (IGFBP) in nervous tissue and is released from the complex via IGFBP proteolysis by specific proteases. It has been reported that IGFBP-2, 5 and 6 are cleaved by specific proteases in the central nervous system (CNS), followed by IGF release; however, it was unknown whether IGFBP-4 was exposed to a particular proteolysis in nervous tissue. Using neurons and astrocytes derived from human induced pluripotent stem cell lines (hiPSC), as well as rat brain-sourced primary neuron-glia cultures, we demonstrated that IGFBP-4 is specifically cleaved in nervous tissue by the Pregnancy Associated Plasma Protein A (PAPP-A) protease and that this cleavage is IGF-dependent. Our results indicate that astrocyte rather than neuron PAPP-A cleaves IGFBP-4 in nervous tissue suggesting that this may be one of the fundamental mechanisms for IGF interchange between these two types of cells., 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 © 2024 Elsevier Inc. All rights reserved.)

Cardiovascular diseases (CVD) are among the leading causes of death and disability worldwide. Pregnancy-associated plasma protein-A (PAPP-A) is a matrix metalloprotease localized on the cell surface. One of the substrates that PAPP-A cleaves is the insulin-like growth factor binding protein-4 (IGFBP-4), a member of the family of proteins that bind insulin-like growth factor (IGF). Proteolysis of IGFBP-4 by PAPP-A occurs at a specific site resulting in formation of two proteolytic fragments - N-terminal IGFBP-4 (NT-IGFBP-4) and C-terminal IGFBP-4 (CT-IGFBP-4), and leads to the release of IGF activating various cellular processes including migration, proliferation, and cell growth. Increased levels of the proteolytic IGFBP-4 fragments correlate with the development of CVD complications and increased risk of death in patients with the coronary heart disease, acute coronary syndrome, and heart failure. However, there is no direct evidence that PAPP-A specifically cleaves IGFBP-4 in the cardiac tissue under normal and pathological conditions. In the present study, using a primary culture of rat neonatal cardiomyocytes as a model, we have demonstrated that: 1) proteolysis of IGFBP-4 by PAPP-A occurs in the conditioned medium of cardiomyocytes, 2) PAPP-A-specific IGFBP-4 proteolysis is increased when cardiomyocytes are transformed to a hypertrophic state. Thus, it can be assumed that the enhancement of IGFBP-4 cleavage by PAPP-A and hypertrophic changes in cardiomyocytes accompanying CVD are interrelated, and PAPP-A appears to be one of the activators of the IGF-dependent processes in normal and hypertrophic-state cardiomyocytes.

Aim      To study features of diagnosis and treatment of acute myocardial infarction (AMI) in Russian hospitals, results of the treatment, and early and late outcomes (6 and 12 months after AMI diagnosis); to evaluate the consistence of the treatment with clinical guidelines; and to evaluate patients' compliance with the treatment.Material and methods  The program was designed for 3 years, including 24 months for recruitment of patients to the study. The study will include 10, 000 patients hospitalized with a confirmed diagnosis (I21 according to ICD-10) of ST segment elevation acute myocardial infarction (MI) (STEMI) or non-ST segment elevation MI (NSTEMI) based on criteria of the European Society of Cardiology Guidelines on Forth Universal Definition of Myocardial Infarction (2018). The follow-up period was divided into three stages: observation during the stay in the hospital and at 6 and 12 months following inclusion into the registry. The primary endpoint included cardiac death, nonfatal MI during the hospitalization and after one-year follow-up. Secondary endpoints were 6-months and one-year incidence of repeated MI, heart failure, ischemic stroke, clinically significant hemorrhage, unscheduled revascularization after discharge from the hospital, and the proportion of patients who continue on statins, antiplatelet drugs, and drugs of other groups for 6 months and 1 year.Results The inclusion of patients into the registry started in 2020 and will continue for 24 months. By the time of the article publication (June, 2021), more than 2,000 patients will be included.Conclusion      REGION-MI (Russian rEGIstry Of acute myocardial iNfarction) is a multicenter, retrospective and prospective observational cohort study that excludes any interference with the clinical practice. Results of the registry will help to analyze a real picture of medical care provided to patients with myocardial infarction and to schedule ways to improve the situation.

Background: Entresto™ is a new heart failure (HF) therapy that includes the neprilysin (NEP) inhibitor sacubitril. One of the NEP substrates is B-type natriuretic peptide (BNP); its augmentation by NEP inhibition is considered as a possible mechanism for the positive effects of Entresto. We hypothesized that the circulating products of BNP proteolysis by NEP might reflect NEP impact on the metabolism of active BNP. We suggest that NEP-based BNP cleavage at position 17-18 results in BNP ring opening and formation of a novel epitope with C-terminal Arg-17 (BNP-neo17 form). In this study, we use a specific immunoassay to explore BNP-neo17 in a rat model and HF patient plasma., Methods: We injected BNP into rats, with or without NEP inhibition with sacubitril. BNP-neo17 in plasma samples at different time points was measured with a specific immunoassay with neglectable cross-reactivity to intact forms. BNP-neo17 and total BNP were measured in EDTA plasma samples of HF patients., Results: BNP-neo17 generation in rat circulation was prevented by NEP inhibition. The maximum 13.2-fold difference in BNP-neo17 concentrations with and without sacubitril was observed at 2 min after injection. BNP-neo17 concentrations in 32 HF patient EDTA plasma samples ranged from 0 to 37 pg/mL (median, 5.4; interquartile range, 0-9.1). BNP-neo17/total BNP had no correlation with total BNP concentration (with r = -0.175, P = 0.680) and showed variability among individuals., Conclusions: BNP-neo17 formation is NEP dependent. Considering that BNP-neo17 is generated from the active form of BNP by NEP, we speculate that BNP-neo17 may reflect both the NEP activity and natriuretic potential and serve for HF therapy guidance., (© 2019 American Association for Clinical Chemistry.)

The long-term (4 weeks) administration of estradiol (15 μg/kg/day) to ovariectomized female Wistar rats induced hypoxic pulmonary hypertension and significantly (p<0.05) diminished relaxation of perfused serotonin-preconstricted isolated vascular segments of the pulmonary artery in response to estradiol (10(-6) M). At the same time, the isolated segments of systemic popliteal artery demonstrated a diminished response to serotonin and increased relaxation induced by acetylcholine (10(-5) M) or estradiol (10(-5) M) in comparison with preconstricted control vessels. Moderation of responsiveness to estradiol in pulmonary circulation can be one of the factors underlying the pro-hypertensive action of estradiol in female rats with hypoxic pulmonary hypertension.

Background: The appearance of B-type natriuretic peptide (BNP) in the blood is ultimately caused by proteolytic processing of its precursor, proBNP. The mechanisms leading to the high plasma concentration of unprocessed proBNP are still poorly understood. The goals of the present study were to examine whether processing of proBNP takes place in the circulation and to evaluate the clearance rate of proBNP and proBNP-derived peptides., Methods: We studied the processing of human proBNP in the circulation and the clearance rate of proBNP and proBNP-derived peptides (BNP and N-terminal fragment of proBNP, NT-proBNP) in rats by injecting the corresponding peptides and analyzing immunoreactivity at specific time points. Glycosylated and nonglycosylated proBNP and NT-proBNP were used in the experiments. We applied immunoassays, gel filtration, and mass spectrometry (MS) techniques to analyze the circulation-mediated processing of proBNP., Results: ProBNP was effectively processed in the circulation into BNP (1-32) and various truncated BNP forms as confirmed by gel filtration and MS analysis. Glycosylation of proBNP close to the cleavage-site region suppressed its processing in the circulation. The terminal half-life for human glycosylated proBNP was 9.0 (0.5) min compared with 6.4 (0.5) min for BNP. For NT-proBNP, the terminal half-lives were 15.7 (1.4) min and 15.5 (1.3) min for glycosylated and nonglycosylated forms, respectively., Conclusions: In rats, processing of human proBNP to active BNP occurs in the circulation. The clearance rate of proBNP is quite similar to that of BNP. These observations suggest that peripheral proBNP processing may be an important regulatory step rather than mere degradation.

Endothelin-1 (ET-1) has been implicated in many cardiovascular diseases, including acute heart failure (AHF) due to myocardial ischemia. Previously we described the oral endothelin-converting enzyme (ECE) inhibitor, PP36, and in this study, we investigated its cardioprotective effect in more detail, and examined the role of PP36 in the neurohormonal activation in rats that had been subjected to acute myocardial ischemia due to the microsphere embolization of coronary microcirculation. PP36 treatment (3.5 x 10(-5) M/kg/day) led to a significant fourfold decrease in hypertensive response when big-ET-1 was administered to healthy, conscious rats. ECE inhibition did not affect mortality during the first 48 hours after ischemia initiation. Systemic hemodynamic, heart function, and neurohormonal activation were analyzed in the healthy control group, the AHF group, and the AHF+PP36 group two days after AHF induction. In conscious rats in the AHF+PP36 group, mean arterial pressure (MAP) was restored and became similar to that of the MAP of the control group. In anesthetized rats, in the AHF+PP36 group, MAP was not restored and was 22% lower than the MAP of the control group. Myocardial contractility was partially restored and cardiac relaxation significantly improved after PP36 application. Further analysis of cardiac output and peripheral resistance in anesthetized rats revealed no differences between the AHF group and the AHF+PP36 group. There were no differences in plasma ET-1 concentration, serum angiotensin converting enzyme activity, and in the adrenal glands' catecholamine content between the AHF group and the AHF+PP36 group. However, rats in the AHF+PP36 group demonstrated a 60% decrease in cardiac endothelial nitric oxide synthase (eNOS) protein expression, and a 56% reduction of myocardial norepinephrine release, when compared with the AHF group's animals. These results suggest that PP36 can preserve heart function during the recovery from acute ischemic injury, and may modulate the cardiac norepinephrine release and eNOS protein level.

Kardos, a preparation containing ultralow doses of antibodies to C-terminal fragment of type 1 receptor of angiotensin II, intragastrically administered to SHR rats with hereditary hypertension for 28 days reduced blood pressure by 14.8%. Kardos was not inferior to losartan and, in contrast to the latter reduced HR by 9.4%.

Exogenous endothelin-1 (ET-1) or high concentrations of the peptide in pathological conditions have marked effects on vascular reactivity. In order to evaluate the role of endogenous ET-1 we investigated responsiveness of conduit (aorta) and of resistant-like (tail artery) vessels in ET-1-deficient rats. Elimination of circulating ET-1 was achieved by active immunization of Wistar rats with a peptide-haemocyanin conjugate (anti-ET-1 group), leading to a marked reduction in plasma level of the peptide in comparison with that of vehicle-treated animals (control group): 1.9 fmol/ml vs 4.9 fmol/ml, respectively. The immunization was associated with a slight elevation of mean arterial pressure, whereas heart rate remained unchanged. In the anti-ET-1 group rings of isolated aorta displayed reduced sensitivity to ET-1: EC50 = 6.57 nM vs 2.95 nM in the control group. Tail arteries of the ET-1-deficient rats showed diminished responses to ET-1, the maximal rise in perfusion pressure: +5.2 mmHg vs +13.6 mmHg in the control group. After immunization, rings of isolated aorta displayed no changes in endothelium-dependent relaxation to acetylcholine (Ach, EC50 = 0.20 microM vs 0.35 microM in the control group), whereas experiments on perfused tail artery showed a twofold reduction in Ach effects. Thus, depletion of circulating ET-1 induces slight changes in haemodynamics associated with altered vessel responsiveness to vasoactive substances.

The endothelin (ET) system was studied in August rats, with genetically determined high sensitivity to stress, and in control Wistar rats. Radioimmunoassay revealed a significant difference in plasma endothelin-1 (ET-1) levels of August vs Wistar rats (7.1 fmol/ml vs 50.0 fmol/ml). Immobilization of the animals increased these values up to 11.0 fmol/ml and 65.2 fmol/ml, respectively. Elevation of ET-1 was associated with an increase in blood pressure, which was similar in both strains, whereas the heart rate increase was diminished in the stress-sensitive rats. The mixed endothelin-A/endothelin-B- (ET(A)/ET(B)) receptor antagonist PD142893 suppressed stress-induced elevation of blood pressure in August, but not in Wistar rats. In both strains, heart rate responses to stress were insensitive to the ET receptor blockade. Aortic rings of August rats displayed diminished sensitivity to the vasoconstrictor action of ET-1 vs that of Wistar rats (EC50 = 22.1 nM vs 6.3 nM, respectively). In noradrenaline-precontracted tail arteries, 50 nM ET-1 elicited further constriction without any vasodilator effects. ET-1-induced increase in perfusion pressure was greater in tail arteries of Wistar rats. Thus, endogenous ET-1 can play a strain-dependent role in the stress-induced responses of haemodynamics and the alterations in endothelin-dependent regulation may be responsible for the differences in vascular reactivity of Wistar and August rats.

We studied the effects of interferon-alpha on rat cardiovascular system. Intravenous administration of intron-A in a dose of 100,000 IU/kg for 3 days led to a permanent and statistically significant decrease in blood pressure (on days 2 and 3) and reduction in heart rate. These effects were not associated with changes in baroreflex regulation of the cardiovascular system.

1. Certain heterocyclic N-oxides are vasodilators and inhibitors of platelet aggregation. The pharmacological activity of the furoxan derivative condensed with pyridazine di-N-oxide 4,7-dimethyl-1,2, 5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide (FPTO) and the corresponding furazan (FPDO) was studied. 2. FPTO reacted with thiols generating nitrite (NO), S-nitrosoglutathione and hydroxylamine (nitroxyl) and converted oxyHb to metHb. FPDO did not generate detectable amounts of NO-like species but reacted with thiols and oxyHb. 3. FPTO and FPDO haem-dependently stimulated the activity of soluble guanylate cyclase (sGC) and this stimulation was inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and by 0.1 mM dithiothreitol. 4. FPTO relaxed noradrenaline-precontracted aortic rings and its concentration-response curve was biphasic (pIC(50)=9. 03+/-0.13 and 5.85+/-0.06). FPDO was significantly less potent vasodilator (pIC(50)=5.19+/-0.14). The vasorelaxant activity of FPTO and FPDO was inhibited by ODQ. oxyHb significantly inhibited only FPTO-dependent relaxation. 5. FPTO and FPDO were equipotent inhibitors of ADP-induced platelet aggregation (IC(50)=0.63+/-0.15 and 0.49+/-0. 05 microM, respectively). The antiplatelet activity of FPTO (but not FPDO) was partially suppressed by oxyHb. The antiaggregatory effects of FPTO and FPDO were only partially blocked by sGC inhibitors. 6. FPTO and FPDO (10 - 20 microM) significantly increased cyclic GMP levels in aortic rings and platelets and this increase was blocked by ODQ. 7. Thus, FPTO can generate NO and, like FPDO, reacts with thiols and haem. The vasorelaxant activity of FPTO and FPDO is sGC-dependent and a predominant role is played by NO at FPTO concentrations below 1 microM. On the contrary, inhibition of platelet aggregation is only partially related to sGC activation.

The aim of this study is to investigate some vasoactive properties of the blood of spontaneously hypertensive rats (SHR). Isolated segments of rat tail arteries obtained from normotensive rats (Wistar-Kyoto (WKY) and Wistar) were perfused with blood from conscious donor rats (WKY, Wistar or SHR). Alterations of the neurogenic constrictor responses (NCR) of the isolated segments evoked by electrical stimulation were studied. The amplitude of NCR of the isolated arteries was studied during perfusion with blood according to the perfusion scheme WKY1(1)-SHR1(2)-WKY1(3) and WKY1(1)-WKY2(2)-WKY1(3). The release of 3H-noradrenaline ([3H]-NA) from vascular sympathetic fibres was measured. The influence of adrenal demedullation on NCR was estimated. We have shown that NCR of isolated arteries decreased by 28.3 +/- 7.9% (P < 0.05 vs. WKY1(1)) during perfusion with blood from SHR (scheme WKY1(1)-SHR1(2)-WKY1(3)). In these experiments, release of [3H]-NA from sympathetic fibres of the artery segments decreased by 39.9 +/- 9.6% during the perfusion with blood from SHR vs. WKY1(1) (P < 0.05). Adrenal demedullation prevented the decrease of NCR during perfusion of the arteries with blood from SHR. In conclusion, the blood of SHR has some antihypertensive factor(s), which causes decrease of NCR in the tail artery from normotensive rats. This decline is accompanied by the decrease of release in [3H]-NA from the transmural sympathetic fibres and is abolished after adrenal demedullation of blood donor rats.

In the present study we investigated the chronopharmacological dependence of dose-dependent hypotensive and cardiochronotropic effects of the imidazoline-like drugs (clonidine, rilmenidine and moxonidine) in stroke-prone spontaneously hypertensive rats (SHR-SP), using radio-telemetric system (Data Sciences, USA). The 24-h blood pressure, heart rate and locomotor activity profiles showed peak values during the rats' active phase during the night period. The degree of hypotensive and bradycardic effects of all drugs were most evident at this time and occurred in the absence of a change in locomotor activity. These studies show that clonidine, rilmenidine and moxonidine decrease blood pressure and heart rate in a time-dependent manner in SHR-SP. It was demonstrated that the degree and duration of hypotensive action of imidazoline-like drugs vary with the time of drug administration.

Earlier findings have shown that hypotensive effects of centrally acting drugs, such as clonidine, are enhanced in animals after denervation of arterial baroreceptors. The purpose of this study was to investigate the dynamic of changes in arterial pressure, heart rate and hypotensive effects of clonidine, rilmenidine and moxonidine in Wistar rats after sino-aortic denervation (SAD) using radio-telemetry. SAD was followed by significant elevation of arterial pressure lability (the standard deviation of the mean arterial pressure), while the baseline mean arterial pressure (MAP) and heart rate in barodenervated rats (12 days after SAD) was similar to intact rats. The hypotension produced by clonidine, rilmenidine and moxonidine was much greater in SAD rats than in intact rats. The study suggests that baroreflex mechanisms are not only important for maintaining levels of blood pressure in the very short term, but also for buffering the effects of centrally acting antihypertensive drugs.

The changes in conductivity of skeletal muscle vessels of the hind leg and tissue-type plasminogen activator (t-PA) activity in outflowing blood after electrostimulation (5 V, 0.5 ms, 20 Hz, 30 s) at the L4-L5 level of the peripheral end of the transected isolated sympathetic chain were studied in experiments on anaesthetized cats. Stimulation of the sympathetic chain induced vasoconstriction and release of t-PA from the vascular wall into the blood. Pretreatment with the beta-adrenoblocker propranolol neither changed the character of vascular reactions nor blocked t-PA secretion. Efferent stimulation of the sympathetic chain against a background of alpha-adrenoceptor blockade by dihydroergotoxin increased blood flow and was accompanied by a rise in t-PA activity. The M-cholinergic blocker atropine suppressed both vascular relaxation and release of t-PA into the blood. Vasodilatation accompanied by t-PA secretion could be induced by intraarterial infusion of acetylcholine and blocked by atropine. The existence of a neurogenic mechanism controlling t-PA release from the vascular wall involving a sympathetic cholinergic pathway and connected with excitation of vascular M-cholinoceptors by acetylcholine is suggested.