Nitrogen Oxide Synthesis Research Articles

Nitrogen Oxide (NO) in the Pathogenesis of Preeclampsia.

The concentrations of nitric oxide (NO) donors in the plasma of pregnant women with preeclampsia is several times higher than in healthy pregnant women. Antihypertensive drugs acting not through the NO-mediated mechanisms normalized BP in some women with preeclampsia, but did not significantly reduce the levels of NO donors in the plasma. It appears that preeclampsia is associated with insufficient NO availability for the targets, rather than low intensity of NO synthesis. The concentration of NO donor molecules in the plasma can therefore be a useful additional diagnostic marker of preeclampsia.

Activating the iNOS regulatory pathway by arginine deprivation targets energy metabolism to induce autophagy-dependent apoptosis against spinal echinococcosis

Spinal echinococcosis is one of the most overlooked zoonotic parasitic diseases worldwide. There is currently no safe and effective treatment to eradicate it, and research based on the physiological-metabolic signature of the disease is lacking. Herein, we repurposed agrimol B as a potent anti-hydatid compound and validated its pharmacological mechanism based on arginine uptake as a target through multi-omics sequencing. This herbal component suppressed energy metabolism and activated ROS aggregation by inducing mitochondrial membrane potential depolarization, which subsequently triggered autophagy-dependent apoptosis leading to parasite death. Moreover, we discovered that arginine deprivation induced metabolic changes led to a shift from ornithine to nitrogen oxide synthesis, thus boosting the iNOS enzyme-regulated dominant metabolic pathway. The excess NO targeted the mitochondrial respiratory chain complex IV to disrupt energy metabolic homeostasis and induced a downstream pathological waterfall effect to kill the hydatid. A novel metabolic regulatory mechanism targeting mitochondrial damage for arginine starvation therapy was discovered. Finally, arginine depletion was found to be superior to the anti-spinal echinococcosis effect of albendazole and accompanied by the potential for disc protection. This study unveils the role of arginine in the physiological metabolism of Echinococcus granulosus and reveals the value of targeting arginine metabolism as a potential therapy. In addition, agrimol B is proposed as a promising therapeutic strategy for spinal echinococcosis to block arginine uptake and break this parasite’s metabolic balance.

The relationship of asymmetric dimethylarginine levels with uncontrolled arterial hypertension and hypertension disease stage

Background: Patients with treatment-resistant hypertension have a worse cardiovascular prognosis compared to those who achieve their target levels of blood pressure (BP). One of biochemical and clinical markers of a decreased response to antihypertensive therapy can be asymmetric dimethylarginine (ADMA), a molecule that reduces formation of nitric oxide and promotes endothelial dysfunction and vasoconstriction.
 Aim: To assess the status of the nitrogen oxide synthesis system and clinical and laboratory profile in patients, depending on the hypertensive disease stage, who achieved or not achieved their target BP levels during hospitalization.
 Materials and methods: We performed аn observational retrospective uncontrolled study in a consecutive sample of 192 patients aged 45–65 years who were admitted to the City Clinical Hospital No. 25 (city of Novosibirsk) with a diagnosis of uncomplicated hypertensive crisis. On the day of discharge, the patients were retrospectively divided into 2 groups. Group 1 included patients who achieved their target BP during hospitalization (target BP group, n = 116). Group 2 included patients with uncontrolled hypertension, in whom the administration of three antihypertensive drugs including a diuretic in optimal or maximal tolerated doses did not result in the achievement of the target BP below 140 and/or 90 mm Hg during hospitalization (non-target BP group, n = 76).
 The following parameters were measured: ADMA, symmetrical dimethylarginine (SDMA), N-monomethyl-L-arginine (NMMA), and total nitric oxide.
 Results: Serum ADMA concentrations (Me [Q25%; Q75%] were increasing with the stage of hypertension: stage I, 0.75 µmol/L [0.66; 0.78], stage II, 1.14 µmol/L [0.87; 1.39], stage III, 1.38 µmol/L [1.22; 1.49] (p 0.0001, Kruskal-Wallis test). In the pairwise comparison, the difference between all these subgroups was significant at p 0.01. In the patients with uncontrolled arterial hypertension ADMA levels were increased compared to those in the target BP group: 1.2 µmol/L [0.99; 1.47] vs 1.07 [0.79; 1.34] µmol/L (p = 0.002). The proportion of patients with type 2 diabetes mellitus among those with uncontrolled arterial hypertension was 31.2% (24/76), while in the target BP group there were only 3.5% of such patients (4/116) (odds ratio 12.57, 95% confidence interval 4.15–38.05; p = 0.00001).
 Conclusion: ADMA measurement may help identify patients with a potential poor response to antihypertensive therapy. This should be taken into account when choosing a treatment regimen and BP monitoring. In addition, ADMA seems to be a promising target for the development of new drug classes.

Metabolic biomarkers for Alzheimer's disease: A mini review

Alzheimer's disease (AD) is the most common neurodegenerative disorder and a leading cause of dementia worldwide, which characterized by progressive cognitive decline, memory impairment, and changes in behavior and personality. The prevalence of AD is expected to rise significantly in the coming decades due to the aging population, making it a major public health concern. Mounting evidence suggests that metabolic dysregulation plays a critical role in the pathogenesis of AD. In this mini review, we provide an overview of the current understanding of the interplay between metabolism and AD. Specifically, we explore the dysregulation of glucose metabolism, lipid metabolism, amino acid metabolism, and nitrogen oxide synthesis pathways in AD. These metabolic alterations have been identified as potential biomarkers for early diagnosis and prognosis of AD. Additionally, we discuss the current status of research in this field, including the advancements in metabolomics and imaging techniques that have allowed for the identification and validation of metabolic biomarkers.

Brief description of the synthesis of new nitrogen oxides

Cancer is one of the major diseases that endanger human life and health. Common anticancer drugs have high side effects and are prone to drug resistance, leading to treatment failure. Due to their special structures and lipophilicity, cage compounds have more pharmacological activities in their derivatives, such as antiviral, immune enhancing, and antitumor activities. Scientists have used cage compounds with good lipophilicity as structural units to develop new drugs with good selectivity, high efficiency and low toxicity. nIT-like nitroxide radicals have excellent antitumor activity, and this paper reviews the investigation of introducing cage structures into NIT-like nitroxide radicals to design and synthesize novel nitrogen oxides.

Effect of Bacillus Subtilis on Immune Function of Hd11 Chicken Macrophages

Poultry is frequently contaminated by Salmonella, a pathogen leading to human health concern worldwide. This study aimed to evaluate the effect of Bacillus subtilis (BS)strain 048 (BS048) on the activation, phagocytosis, sterilization, cytokine secretion, and nitrogen oxide synthesis of HD11 chicken macrophages subjected to Salmonella enteritidis challenge, using lipopolysaccharide treatment as a negative control. The results showed: (1) BS048 had no significant effect on extracellular lactate dehydrogenase activity (p>0.05), while lipopolysaccharide treatment significantly increased extracellular lactate dehydrogenase activity (p<0.05);(2)BS048 significantly upregulated the expression levels of pro-inflammatory cytokines (interleukin (IL)-1â and IL-6), anti-inflammatory cytokines(IL-10 and transforming growth factor-â1), and anti-viral cytokine, interferon-â (p<0.01); (3)BS048 significantly upregulated the mRNA expression level of the inducible nitric oxide synthase and its activity as well as extracellular nitrogen oxide level (p<0.01). In conclusion, BS048 could improve anti-inflammatory and immune functions of HD11 chicken macrophages, without cytotoxic effects on these cells.

Investigation of the Quenching of Nitrogen Oxide Synthesis Products in Air Plasma

The paper presents the results of theoretical and experimental studies of the quenching process of nitrogen oxide synthesis products in a low-temperature air plasma. A developed experimental setup for researching the quenching consists of an air plasma generator with a power of up to 40 kW, as well as a coolant feeding system and control and measuring equipments. For the mathematical modeling of the processes, the numerical solution of the system of differential equations of conservation of mass, momentum, and energy in a turbulent system is used. Calculations and experiments were carried out in the range of variation of the quenching air flow rate 1–5 g/s at a plasma power of 31 kW, and a plasma air flow rate of 5 g/s. The calculated data on the values of heat fluxes are in satisfactory agreement with the experimental values. The theoretically and experimentally obtained value of the average cooling rate of the synthesis products 2.9 × 105 K/s significantly exceeds the cooling rate with traditional water cooling of elements.

Sodium Hydrosulfide Induces Resistance Against Penicillium expansum in Apples by Regulating Hydrogen Peroxide and Nitric Oxide Activation of Phenylpropanoid Metabolism.

As a multifunctional signaling molecule, hydrogen sulfide (H2S) has been reported to induce plant responses to a variety of abiotic stresses. However, there are no reports on H2S treatment inducing resistance in apples against Penicillium expansum, a biotic factor, and its possible mechanism of action. In this study, fumigating apples with 5 mM sodium hydrosulfide (NaHS), the exogenous donor of H2S, for 12 h reduced the diameter of lesions in fruit colonized by P. expansum. NaHS treatment markedly promoted the synthesis of endogenous H2S, hydrogen peroxide (H2O2), and nitrogen oxide (NO). In vivo NaHS treatment enhanced the activities of phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, p-coumarate:coenzyme A ligase isoenzymes, caffeoyl-CoA-O-methyltransferase, caffeic acid-O-methyltransferase, ferulic acid-5-hydroxylase, cinnamyl-CoA reductase, and cinnamyl-alcohol dehydrogenase. The treatment also facilitated the production of specific phenolic acids, such as cinnamic acid, p-coumaric acid, caffeic acid, ferulic acid, and sinapic acid; total phenolic compounds; p-coumaryl alcohol; coniferyl alcohol; sinapyl alcohol; and lignin. NaHS treatment induced resistance against P. expansum in apples through H2O2- and NO-mediated activation of phenylpropanoid metabolism.

Synthesis of Nitrogen and Phosphorus Dual-Doped Graphene Oxide as High-Performance Anode Material for Lithium-Ion Batteries.

Nitrogen and phosphorus dual-doped graphene oxide was prepared by directly calcining a mixture of pure graphene oxide, urea (nitrogen source), and 1,2-bis(diphenylphosphino)methane (phosphorous source). The morphology and composition of the obtained dual-doped graphene oxide were confirmed by SEM, TEM, XRD pattern, Raman spectrum, and XPS. The nitrogen and phosphorous dual-doped graphene oxide was tested as an anode material of lithium-ion batteries (LIBs). The cycle and rate performance of the dual-doped graphene oxide were also examined. The dualdoped graphene oxide exhibited a superior initial discharge capacity of 2796 mAh·g-1 and excellent reversible capacity of 1200 mAh·g-1 at a current density of 100 mA·g-1 after 200 charge/discharge cycles, suggesting that the dual-doping of nitrogen and phosphorous is an effective way to enhance lithium-ion storage for graphene oxide.

The role of gas mediators of nitrogen (II) oxide and hydrogen sulfide in the development of pathochemical changes in the mucous membrane of rats at water-immobilization and adrenaline-induced stress modeling

Acute and prolonged psycho-emotional overstrain, i.e. stress, are the most frequent factors of ulcer formation in the digestive system. Therefore, the study of molecular mechanisms of stress impact is one of the most promising directions of modern experimental gastroenterology. However, the features of its molecular-biochemical action on the metabolic processes in the digestive system remain insufficiently studied. In this regard, we performed a comparative analysis of changes in indicators of systems of gas mediators of nitrogen (II) oxide and hydrogen sulfide synthesis at water-immobilization and adrenaline-induced stress modeling in experiments on white non-linear rats. Water-immobilization stress (WIS) was modelled by immobilizing animals in a plastic container, and adrenaline-induced stress (AIS) was modelled by injecting adrenaline at a dose of 2 mg/kg intraperitoneally. Modelling WIS caused formation of erosion and spot hemorrhage, located mainly along the folds of the fundus of the stomach. In this case, more noticeable changes were observed in the 5-hour WSI model. Injecting adrenaline at AIS model caused development of structural-hemorrhagic damage in the pyloric part and body of the stomach. The biochemical response to stress is complex, and the release of catecholamines is not the only case of stress. The synthesis of hormones such as glucagon, somatotropin and renin is activated. However, the most important role is played by cortisol, which level of growth in blood is measured to assess the degree of stress development. In our studies, changes in cortisol level in blood under different types of stress modeling (WIS and AIS) had their own peculiarities: at WIS conditions cortisol concentration increased sharply and remained high for 5 hours, while adrenaline did not cause the growth of this “stress hormone”. In our studies, in both models of stress-induced ulcerogenesis there were significant changes to the content of H2S and NO, that confirms the significant role of these substances in development and progression of ulcerogenesis in the digestive system. Thus, H2S concentration decreased at WIS and AIS. There is a significant increase in nitrogen oxide production in both WIS with different duration of action and AIS, which is caused by multiple activation of the inducible isoform of NO-synthase. Therefore, in experimental stress-induced ulcerogenesis, the metabolism of L-arginine in the mucous membrane of stomach is equally shifted towards the formation of NO, that under conditions of strengthening of free radical processes serves as a prerequisite for activation of oxidative-nitric processes and leads to the formation of structural-hemorrhagic damage to the surface of the mucous membrane of stomach. Our studies also show that ulcerative damage to the mucous membrane of stomach in all the types of studied stress was accompanied by an increase in myeloperoxidase activity, indicating an increase in permeability of hemocapillaries due to the development of the inflammatory process.

Pulse–Periodic Diffuse Discharge with Self-Ionization in a Gas Flow

A pulse–periodic diffuse discharge self-initiated in an atmospheric-pressure air flow passing through an annular gap with a strongly nonuniform electric field has been studied. The discharge serves as a source of a weakly ionized nonequilibrium plasma in which effective synthesis of nitrogen oxide is provided. It has been found that diffuse current channels sequentially arise in the annular gap in the direction of the air flow in time with high-voltage pulses. Experimental data suggest that the self-ionization (self-initiation) effect is due to the shift of negative oxygen ions accumulated in current channels and the mechanism behind the appearance of “seed” electrons in breakdown areas is the detachment of electrons from oxygen ions.

Synthesis of Nitrogen Oxides in a Subthreshold Microwave Discharge in Air and in Air Mixtures with Methane

A subthreshold discharge excited by a microwave beam in air at pressures close to atmospheric is studied as a plasmachemical method of nitrogen oxide (NOx) production. It is shown that at the energy expenditure level (2–4) kW h/m3, it is possible to produce a nitrogen oxide concentration in pure air that exceeds the concentration in the initial gas by several orders of magnitude. At the same time, it is shown that it is possible to stop nitrogen oxide production almost completely by adding an admixture of methane (CH4) to the irradiated air, which makes the so-called self-non-self-sustained (SNSS) discharge much more promising for cleaning the gaseous exhausts from urban landfills from harmful admixtures (hydrogen sulfide, mercaptans, etc.).

Hydrothermal processing of β-glucan from Aureobasidium pullulans produces a low molecular weight reagent that regulates inflammatory responses induced by TLR ligands

The Kururu no β-glu® (KBG) is a commercial hydrothermal-treated Aureobasidium pullulans β-glucan produced by a unique hydrothermal process that results in high solubility of the β-glucan. In this study, we examined the biological activities of this reagent. RAW264.7 cells do not express Dictin-1 on the cell surface, but cells still respond to various pathogen molecular patterns. Lipopolysaccharide (LPS) induced nitrogen oxide (NO) synthesis and TNF−α production in RAW264.7 cells, and those were suppressed by KBG in a dose-dependent manner. The major signaling cell surface receptor respond to LPS is the TLR4/MD-2 complex. The UT12 antibody against to the TLR4/MD-2 complex mimics LPS function and induces cell responses. NO generation and TNF-α production were similarly induced in cells by stimulation with the antibody, but those were not suppressed by KBG. Cell responses induced by other TLR ligands, such as CPG (TLR9 ligand) and Pam3CSK4 (TLR1/TLR2 ligand), were also suppressed by KBG. Therefore, the target molecule for KBG is different from TLR receptors and Dictin-1. Although we also examined the suppressive activities of several other β-glucan products, comparable activities were not detected with other reagents. A unique hydrothermal process may produce the active reagent. Reprocessing KBG increased low molecular weight fractions, and suppressive activities were markedly enhanced. Therefore, low molecular weight fractions obtained by hydrothermal processing of KBG may result in potential reagents that control inflammation induced by various pathogens.

Synthesis of Nitrogen Oxides in ICP/RF Plasma

This paper presents the results of investigation of the possibilities to produce high volume and concentration of nitrogen oxides in inductively coupled plasma/radio frequency plasma for industrial applications. Calculations of the equilibrium composition of air and air–oxygen plasma at different temperatures and pressures have been conducted. The data obtained can be used to design and develop efficient systems for the nitrogen oxides synthesis.

Ultrasound-Assisted Nitrogen and Boron Codoping of Graphene Oxide for Efficient Oxygen Reduction Reaction

Development of naturally abundant, low cost, and energy-efficient electrocatalysts for the oxygen reduction reaction (ORR) is essential for commercialization of fuel cells. In this work, we report simple ultrasonication assisted synthesis of nitrogen and boron dual-doped graphene oxide (NB/GO) and demonstrate its application as an effective ORR catalyst realizing predominantly 4e– reduction of O2 to OH– in 0.1 M KOH. Enhanced ORR electrocatalysis of the dual B and N codoped GO as opposed to GO singly doped with B or N arises from the synergistic interaction of the boron and nitrogen species. The content and configuration of both N and B dopants can be readily tailored by controlling the ultrasonic conditions, thereby permitting tuning of the ORR activity. Furthermore, the developed NB/GO metal-free catalyst exhibited very promising long-term durability and resistance to methanol poisoning compared to the state-of the art Pt/C catalyst.

ВПЛИВ ПРЕПАРАТУ L-АРГІНІНУ НА ЗМІНИ ПРОЦЕСІВ ПЕРОКСИДНОГО ОКИСНЕННЯ ЛІПІДІВ ТА АНТИОКСИДАНТНОЇ СИСТЕМИ В КРОВІ ЗА УМОВ КОМОРБІДНОЇ ПАТОЛОГІЇ – ІММОБІЛІЗАЦІЙНОГО СТРЕСУ ТА АДРЕНАЛІНОВОГО УШКОДЖЕННЯ МІОКАРДА

Вступ. Активація адренергічної і гіпоталамо-гіпофізарно-адреналової систем призводить до виникнення стресорної тріади Сельє, першим компонентом якої є гіпертрофія надниркових залоз із збільшенням синтезу ними глюкокортикоїдів та катехоламінів. Аргінін слугує необхідним компонентом для синтезу білків і багатьох біологічно важливих молекул, таких, як орнітин, пролін, поліаміни, креатин і агматин. Однак головна його роль в організмі людини – бути субстратом для синтезу оксиду азоту. &#x0D; Мета дослідження –вивчити вплив препарату L-аргініну на зміни процесів пероксидного окиснення ліпідів та антиоксидантної системи, що виникають у крові білих щурів під впливом гострого іммобілізаційного стресу й адреналіну.&#x0D; Методи дослідження.Дослід проводили на білих щурах-самцях лінії Вістар масою 180–200 г, яких було поділено на три групи по 10 тварин у кожній (дві дослідні та одну контрольну).&#x0D; Результати й обговорення. Встановлено, що за умов поєднаної патології (іммобілізаційного стресу й адреналінового ушкодження міокарда) до лікування L-аргініном активність у крові показників антиоксидантної системи – каталази і супероксиддисмутази зменшувалася на 5-ту добу експерименту. Було відзначено збільшення рівня продуктів пероксидного окиснення ліпідів – дієнових кон’югатів та малонового діальдегіду проти контролю. Використання L-аргініну протягом 5-ти днів призвело до підвищення активності каталази (на 107,2 %) і супероксиддисмутази (на 74,5 %) відносно групи тварин з поєднаною патологією в експерименті (іммобілізаційним стресом і адреналіновим ушкодженням міокарда) до лікування, що свідчить про антиоксидантний вплив даного препарату. Застосування L-аргініну протягом 5-ти днів знизило рівень дієнових кон’югатів (на 80,16 %, р&lt;0,05) та малонового діальдегіду (на 42,26 %, р&lt;0,05), що вказує на зменшення процесів пероксидного окиснення ліпідів. &#x0D; Висновок.L-аргінін доцільно в подальшому і перспективно вивчати в експерименті та клініці з метою корекції метаболічних порушень за умов експериментального іммобілізаційного стресу й адреналінового ушкодження міокарда і розробки методичних рекомендацій.

Стан системи нітроген (ІІ) оксиду в щурів з пародонтитом на фоні гіпер- та гіпотиреозу

Introduction. Inflammatory periodontal disease is one of the most urgent problems of dentistry, which has a social significance due to the high prevalence, pronounced changes in the tissues of the periodontal disease and the body of the patient as a whole, and the defeat of young people.The aim of the study – to investigate the functional state of the nitrogen (II) oxide system in rats with periodontitis without concomitant pathology and against the background of hyper- and hypothyroidism.Research Methods. The study was carried out on 48 white non-linear male rats. The total activity of NO-synthase (NOS) was determined colorimetrically by the number of formed nitrates and nitrites in the incubation medium. The total content of nitrates and nitrites (NOx) was determined by the Gris method.Results and Discussion. Experimental periodontitis is accompanied by increased general activity of NO-synthase in periodontal tissue homogenate by 2.2 times vs control. NOx content in the serum of animals with periodontitis increased by 46.2% and in the periodontal tissue homogenate – by 74.7% compared with the control. In rats with periodontitis against hyperthyroidism, NOS activity increased by 3.9 times relative to the control group of animals and by 75.9% exceeded the rate of rats with periodontitis without concomitant pathology. In rats with periodontitis, against the background of hypothyroidism, the activity of NOS was 29.6% higher than that of rats with periodontitis without concomitant pathology and 2.9-fold of control.Conclusions. Experimental periodontitis is accompanied by a marked increase in the intensity of nitroxidergic processes both in the homogenate of periodontal tissues and in the blood. The imbalance of thyroid hormones increases the synthesis of nitrogen (II) oxide in the experimental periodontitis, especially expressed in hyperthyroidism.

The expediency of application of metabolic therapy for correcting changes of the myocardium on the background of diabetes mellitus

The published data about basic pathogenetic mechanisms of myocardial abnormalities due to diabetes, damage of cardiomyocytes and neurovegetative microcirculatory disorders.The expediency of application of metabolic therapy for correction these disorders, in particular, the amino acid L-arginine (Tivortin®) – substrate for nitrogen oxide synthesis.

Nitrogen Fixation by Gliding Arc Plasma: Better Insight by Chemical Kinetics Modelling.

The conversion of atmospheric nitrogen into valuable compounds, that is, so-called nitrogen fixation, is gaining increased interest, owing to the essential role in the nitrogen cycle of the biosphere. Plasma technology, and more specifically gliding arc plasma, has great potential in this area, but little is known about the underlying mechanisms. Therefore, we developed a detailed chemical kinetics model for a pulsed-power gliding-arc reactor operating at atmospheric pressure for nitrogen oxide synthesis. Experiments are performed to validate the model and reasonable agreement is reached between the calculated and measured NO and NO2 yields and the corresponding energy efficiency for NOx formation for different N2 /O2 ratios, indicating that the model can provide a realistic picture of the plasma chemistry. Therefore, we can use the model to investigate the reaction pathways for the formation and loss of NOx . The results indicate that vibrational excitation of N2 in the gliding arc contributes significantly to activating the N2 molecules, and leads to an energy efficient way of NOx production, compared to the thermal process. Based on the underlying chemistry, the model allows us to propose solutions on how to further improve the NOx formation by gliding arc technology. Although the energy efficiency of the gliding-arc-based nitrogen fixation process at the present stage is not comparable to the world-scale Haber-Bosch process, we believe our study helps us to come up with more realistic scenarios of entering a cutting-edge innovation in new business cases for the decentralised production of fertilisers for agriculture, in which low-temperature plasma technology might play an important role.

Development of endothelial dysfunction at an obliterating atherosclerosis of vessels of the lower extremities and markers of prediction of a course of a disease

In this review questions of development of endothelial dysfunction and its influence on progressing of a disease at an obliterating atherosclerosis of vessels of the lower extremities are considered. The role of selektin in adhesion of leukocytes on the endothelial cells leading to inflammatory reaction of a vascular wall is defined. In researches influence of the infectious agent on risk of development of a disease is noted. Decrease in dilatiruyushchy function of an endothelium happens due to deficiency of synthesis of nitrogen oxide. Development of an oxidizing stress and development of the fissile forms of oxygen exerts negative impact on an endothelium. The indicators associated with an atherosclerosis are inflammation mediators, markers of endothelial dysfunction and an angiogenesis, a lipide profile and factors of coagulation.