Activation of Transcription Factor Nrf2 in HeLa Cells under the Action of Nitrosyl Iron Complex with N-Ethylthiourea.

We studied the effect of an NO donor, nitrosyl iron complex with N-ethylthiourea, on Nrf2-dependent antioxidant system activation of tumor cells in vitro. The complex increased intracellular accumulation of Nrf2 transcription factor and induced its nuclear translocation. It was shown that both heme oxygenase-1 gene and protein expression increased significantly under the influence of the complex. Nrf2 activation was accompanied by a decrease in the intracellular accumulation of proinflammatory transcription factor NF-κB p65 subunit and expression of its target genes. The cytotoxic effect of N-ethylthiourea leads to induction of Nrf2/HO-1 antioxidant response and suppression of NF-κB-dependent processes in tumor cells.

HBB contributes to individualized aconitine-induced cardiotoxicity in mice via interfering with ABHD5/AMPK/HDAC4 axis.

The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.

Oxygen-binding properties of blood in insulin resistance with different asprosin content.

The oxygen-binding properties of blood were studied in male patients with insulin resistance (IR) with different levels of asprosin. The content of asprosin, parameters of blood oxygen transport function, as well as gas transmitters, nitrogen monoxide and hydrogen sulfide, were determined in the venous blood plasma. In the studied IR patients with increased blood asprosin content, impaired blood oxygenation was noted; IR patients with normal body weight had increased hemoglobin affinity for oxygen, while in IR patients with overweight and the 1st degree obesity, this parameter decreased. The detected increase in the concentration of nitrogen monoxide and the decrease in hydrogen sulfide may be important for the oxygen-binding properties of the blood and the development of metabolic imbalance.

Association between short-term exposure to environmental air pollution and atopic dermatitis flare in patients treated with dupilumab.

Background: The magnitude of short/medium-term air pollution exposure on atopic dermatitis (AD) flare has not been fully investigated. The aim of the study was to investigate the association of short/medium-term exposure to airborne pollution on AD flares in patients treated with dupilumab. Methods: Observational case-crossover study. Patients with moderate-to-severe AD under treatment with dupilumab were included. The exposure of interest was the mean concentrations of coarse and fine particulate matter (PM10, PM2.5), nitrogen dioxide, and oxides (NO2, NOx). Different intervals were considered at 1 to 60 days before the AD flare and control visit, defined as the visit with the highest Eczema Area and Severity Index scores >8 and ≤7, respectively. A conditional logistic regression analysis adjusted for systemic treatments was employed to estimate the incremental odds (%) of flare every 10 µg/m3 pollutant concentration. Results: Data on 169 of 528 patients with AD having 1130 follow-up visits and 5840 air pollutant concentration measurements were retrieved. The mean age was 41.4 ± 20.3 years; 94 (55%) men. The incremental odds curve indicated a significant positive trend of AD flare for all pollutants in all time windows. At 60 days, every 10 µg/m3 PM10, PM2.5, NOx, and NO2 increase concentration was associated with 82%, 67%, 28%, and 113% odds of flare, respectively. Conclusions: In patients treated with dupilumab, acute air pollution exposure is associated with an increased risk for AD flare with a dose-response relationship.

Spectroscopy of Laser-Induced Dielectric Breakdown Plasma in Mixtures of Air with Inert Gases Ar, He, Kr, and Xe.

The generation of ozone and nitrogen oxides by laser-induced dielectric breakdown (LIDB) in mixtures of air with noble gases Ar, He, Kr, and Xe is investigated using OES and IR spectroscopy, mass spectrometry, and absorption spectrophotometry. It is shown that the formation of NO and NO2 noticeably depends on the type of inert gas; the more complex electronic configuration and the lower ionization potential of the inert gas led to increased production of NO and NO2. The formation of ozone occurs mainly due to the photolytic reaction outside the gas discharge zone. Equilibrium thermodynamic analysis showed that the formation of NO in mixtures of air with inert gases does not depend on the choice of an inert gas, while the equilibrium concentration of the NO+ ion decreases with increasing complexity of the electronic configuration of an inert gas.

Blatter Radical-Decorated Silica as a Prospective Adsorbent for Selective NO Capture from Air.

Nitrogen oxides are adverse poisonous gases present in the atmosphere and having detrimental effects on the human health and environment. In this work, we propose a new type of mesoporous materials capable of capturing nitrogen monoxide (NO) from air. The designed material combines the robust Santa Barbara Amorphous-15 silica scaffold and ultrastable Blatter-type radicals acting as NO traps. Using in situ electron paramagnetic resonance spectroscopy, we demonstrate that NO capture from air is selective and reversible at practical conditions, thus making Blatter radical-decorated silica highly promising for environmental applications.

A review: Biological technologies for nitrogen monoxide abatement.

Nitrogen oxides (NOx), including nitrogen monoxide (NO) and nitrogen dioxide (NO2), are among the most important global atmospheric pollutants because they have a negative impact on human respiratory health, animals, and the environment through the greenhouse effect and ozone layer destruction. NOx compounds are predominantly generated by anthropogenic activities, which involve combustion processes such as energy production, transportation, and industrial activities. The most widely used alternatives for NOx abatement on an industrial scale are selective catalytic and non-catalytic reductions; however, these alternatives have high costs when treating large air flows with low pollutant concentrations, and most of these methods generate residues that require further treatment. Therefore, biotechnologies that are normally used for wastewater treatment (based on nitrification, denitrification, anammox, microalgae, and combinations of these) are being investigated for flue gas treatment. Most of such investigations have focused on chemical absorption and biological reduction (CABR) systems using different equipment configurations, such as biofilters, rotating reactors, or membrane reactors. This review summarizes the current state of these biotechnologies available for NOx treatment, discusses and compares the use of different microorganisms, and analyzes the experimental performance of bioreactors used for NOx emission control, both at the laboratory scale and in industrial settings, to provide an overview of proven technical solutions and biotechnologies for NOx treatment. Additionally, a comparative assessment of the advantages and disadvantages is performed, and special challenges for biological technologies for NO abatement are presented.

Raw data collected from NO 2 , O 3 and NO air pollution electrochemical low-cost sensors.

Recently, the monitoring of air pollution by means of low-cost sensors has become a growing research field due to the study of techniques based on machine learning to improve the sensors' data quality. For this purpose, sensors undergo a calibration process, where these are placed in-situ nearby a regulatory reference station. The data set explained in this paper contains data from two self-built low-cost air pollution nodes deployed for four months, from January 16, 2021 to May 15, 2021, at an official air quality reference station in Barcelona, Spain. The goal of the deployment was to have five electrochemical sensors at a high sampling rate of 0.5 Hz; two NO 2 sensors, two O 3 sensors, and one NO sensor. It should be noted that the reference stations publish air pollution data every hour, thus at a rate of 2.7 × 10 - 4  Hz. In addition, the nodes have also captured temperature and relative humidity data, which are typically used as correctors in the calibration of low-cost sensors. The availability of the sensors' time series at this high resolution is important in order to be able to carry out analysis from the signal processing perspective, allowing the study of sensor sampling strategies, sensor signal filtering, and the calibration of low-cost sensors among others.

Chronic kidney disease: Which role for xanthine oxidoreductase activity and products?

The present review explores the role of xanthine oxidoreductase (XOR) in the development and progression of chronic kidney disease (CKD). Human XOR is a multi-level regulated enzyme, which has many physiological functions, but that is also implicated in several pathological processes. The main XOR activities are the purine catabolism, which generates uric acid, and the regulation of cell redox state and cell signaling, through the production of reactive oxygen species. XOR dysregulation may lead to hyperuricemia and oxidative stress, which could have a pathogenic role in the initial phases of CKD, by promoting cell injury, hypertension, chronic inflammation and metabolic derangements. Hypertension is common in CKD patients and many mechanisms inducing it (upregulation of renin-angiotensin-aldosterone system, endothelial dysfunction and atherosclerosis) may be influenced by XOR products. High XOR activity and hyperuricemia are also risk factors for obesity, insulin resistance, type 2 diabetes and metabolic syndrome that are frequent CKD causes. Moreover, CKD is common in patients with gout, which is characterized by hyperuricemia, and in patients with cardiovascular diseases, which are associated with hypertension, endothelial dysfunction and atherosclerosis. Although hyperuricemia is undoubtedly related to CKD, controversial findings have been hitherto reported in patients treated with urate-lowering therapies.

[Features of ozone effect on the oxygen-dependent blood processes under hypercapnia conditions]. / Osobennosti deistviia ozona na kislorodzavisimye protsessy krovi v usloviiakh giperkapnii.

The aim of this work is to study of ozone effect on blood oxygen-dependent processes under hypercapnia conditions. The studied blood samples are pretreated with a hypercapnic gas mixture followed by the addition of ozonized isotonic sodium chloride solution (with an ozone concentration of 6 mg/l), as well as gaseous transmitters donors, nitroglycerin and sodium hydrosulfide. It has been established that hypercapnia enhanced the ozone effect on the blood oxygen transport function and was characterized by the oxyhemoglobin dissociation curve shift to the right, also increased hydrogen sulfide synthesis and absence of changes in the nitrates/nitrites concentration. Under these conditions nitroglycerin and sodium hydrosulfide did not change the parameters of the blood gas transport function, but increased the level of nitrate/nitrite and hydrogen sulfide. Preliminary hypercapnia does not eliminate the activating effect of ozone on the free radical oxidation processes, and the addition of the applied gaseous transmitter donors does not contribute to the regulation of the studied parameters.

Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation.

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.

Disproportionation of Nitric Oxide at a Surface-Bound Nickel Porphyrinoid.

Uncommon metal oxidation states in porphyrinoid cofactors are responsible for the activity of many enzymes. The F430 and P450nor co-factors, with their reduced NiI - and FeIII -containing tetrapyrrolic cores, are prototypical examples of biological systems involved in methane formation and in the reduction of nitric oxide, respectively. Herein, using a comprehensive range of experimental and theoretical methods, we raise evidence that nickel tetraphenyl porphyrins deposited in vacuo on a copper surface are reactive towards nitric oxide disproportionation at room temperature. The interpretation of the measurements is far from being straightforward due to the high reactivity of the different nitrogen oxides species (eventually present in the residual gas background) and of the possible reaction intermediates. The picture is detailed in order to disentangle the challenging complexity of the system, where even a small fraction of contamination can change the scenario.

Disproportionation of Nitric Oxide at a Surface-Bound Nickel Porphyrinoid.

Uncommon metal oxidation states in porphyrinoid cofactors are responsible for the activity of many enzymes. The F430 and P450nor co-factors, with their reduced NiI- and FeIII-containing tetrapyrrolic cores, are prototypical examples of biological systems involved in methane formation and in the reduction of nitric oxide, respectively. Herein, using a comprehensive range of experimental and theoretical methods, we raise evidence that nickel tetraphenyl porphyrins deposited in vacuo on a copper surface are reactive towards nitric oxide disproportionation at room temperature. The interpretation of the measurements is far from being straightforward due to the high reactivity of the different nitrogen oxides species (eventually present in the residual gas background) and of the possible reaction intermediates. The picture is detailed in order to disentangle the challenging complexity of the system, where even a small fraction of contamination can change the scenario.

The Relationship of Glutathione-S-Transferase and Multi-Drug Resistance-Related Protein 1 in Nitric Oxide (NO) Transport and Storage.

Nitric oxide is a diatomic gas that has traditionally been viewed, particularly in the context of chemical fields, as a toxic, pungent gas that is the product of ammonia oxidation. However, nitric oxide has been associated with many biological roles including cell signaling, macrophage cytotoxicity, and vasodilation. More recently, a model for nitric oxide trafficking has been proposed where nitric oxide is regulated in the form of dinitrosyl-dithiol-iron-complexes, which are much less toxic and have a significantly greater half-life than free nitric oxide. Our laboratory has previously examined this hypothesis in tumor cells and has demonstrated that dinitrosyl-dithiol-iron-complexes are transported and stored by multi-drug resistance-related protein 1 and glutathione-S-transferase P1. A crystal structure of a dinitrosyl-dithiol-iron complex with glutathione-S-transferase P1 has been solved that demonstrates that a tyrosine residue in glutathione-S-transferase P1 is responsible for binding dinitrosyl-dithiol-iron-complexes. Considering the roles of nitric oxide in vasodilation and many other processes, a physiological model of nitric oxide transport and storage would be valuable in understanding nitric oxide physiology and pathophysiology.

Preparation, Antioxidant Properties and Ability to Increase Intracellular NO of a New Pyridoxine Derivative B6NO.

In the case of various pathologies, an imbalance between ROS generation and the endogenous AOS can be observed, which leads to excessive ROS accumulation, intensification of LPO processes, and oxidative stress. For the prevention of diseases associated with oxidative stress, drugs with antioxidant activity can be used. The cytotoxic, antioxidant, and NO-donor properties of the new hybrid compound B6NO (di(3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridinium) salt of 2-(nitrooxy)butanedioic acid) were studied. It was determined that B6NO chelates iron ions by 94%, which indicates B6NO's ability to block the Fenton reaction. The hybrid compound B6NO inhibits the process of initiated lipid peroxidation more effectively than pyridoxine. It was shown that B6NO exhibits antioxidant properties by decreasing ROS concentration in normal cells during the oxidative stress induction by tert-Butyl peroxide. At the same time, the B6NO antioxidant activity on tumor cells was significantly lower. B6NO significantly increases the intracellular nitrogen monoxide accumulation and showed low cytotoxicity for normal cells (IC50 > 4 mM). Thus, the results indicate a high potential of the B6NO as an antioxidant compound.

Spatiotemporal correlation of urban pollutants by long-term measurements on a mobile observation platform.

We conducted a three-year campaign of atmospheric pollutant measurements exploiting portable instrumentation deployed on a mobile cabin of a public transport system. Size selected particulate matter (PM) and nitrogen monoxide (NO) were measured at high temporal and spatial resolution. The dataset was complemented with measurements of vehicular traffic counts and a comprehensive set of meteorological covariates. Pollutants showed a distinctive spatiotemporal structure in the urban environment. Spatiotemporal autocorrelations were analyzed by a hierarchical spatiotemporal statistical model. Specifically, particles smaller than 1.1 µm exhibited a robust temporal autocorrelation with those at the previous hour and tended to accumulate steadily during the week with a maximum on Fridays. The smallest particles (mean diameter 340 nm) showed a spatial correlation distance of ≈600 m. The spatial correlation distance reduces to ≈ 60 m for particle diameters larger than 1.1 µm, which also showed peaks at the stations correlated with the transport system itself. NO showed a temporal correlation comparable to that of particles of 5.0 µm of diameter and a correlating distance of 155 m. The spatial structure of NO correlated with that of the smallest sized particles. A generalized additive mixed model was employed to disentangle the effects of traffic and other covariates on PM concentrations. A reduction of 50% of the vehicles produces a reduction of the fine particles of -13% and of the coarse particle number of -7.5%. The atmospheric stability was responsible for the most significant effect on fine particle concentration.

Kinetic inequivalence between α and ß subunits of ligand dissociation from ferrous nitrosylated human haptoglobin:hemoglobin complexes. A comparison with O2 and CO dissociation.

Haptoglobin (Hp) counterbalances the adverse effects of extra-erythrocytic hemoglobin (Hb) by trapping the αß dimers of Hb in the bloodstream. In turn, the Hp:Hb complexes display Hb-like reactivity. Here, the kinetics of NO dissociation from ferrous nitrosylated Hp:Hb complexes (i.e., Hp1-1:Hb(II)-NO and Hp2-2:Hb(II)-NO, respectively) are reported at pH 7.0 and 20.0 °C. NO dissociation from Hp:Hb(II)-NO complexes has been followed by replacing NO with CO. Denitrosylation kinetics of Hp1-1:Hb(II)-NO and Hp2-2:Hb(II)-NO are biphasic, the relative amplitude of the fast and slow phase being 0.495 ± 0.015 and 0.485 ± 0.025, respectively. Values of koff(NO)1 and koff(NO)2 (i.e., (6.4 ± 0.8) × 10-5 s-1 and (3.6 ± 0.6) × 10-5 s-1 for Hp1-1:Hb(II)-NO and (5.8 ± 0.8) × 10-5 s-1 and (3.1 ± 0.6) × 10-5 s-1 for Hp2-2:Hb(II)-NO) are unaffected by allosteric effectors and correspond to those reported for the α and ß subunits of tetrameric Hb(II)-NO and isolated α(II)-NO and ß(II)-NO chains, respectively. This highlights the view that the conformation of the Hb α1ß1 and α2ß2 dimers matches that of the Hb high affinity conformation. Moreover, the observed functional heterogeneity reflects the variation of energy barriers for the ligand detachment and exit pathway(s) associated to the different structural arrangement of the two subunits in the nitrosylated R-state. Noteworthy, the extent of the inequivalence of α and ß chains is closely similar for the O2, NO and CO dissociation in the R-state, suggesting that it is solely determined by the structural difference between the two subunits.

Looking Back at the Early Stages of Redox Biology.

The beginnings of redox biology are recalled with special emphasis on formation, metabolism and function of reactive oxygen and nitrogen species in mammalian systems. The review covers the early history of heme peroxidases and the metabolism of hydrogen peroxide, the discovery of selenium as integral part of glutathione peroxidases, which expanded the scope of the field to other hydroperoxides including lipid hydroperoxides, the discovery of superoxide dismutases and superoxide radicals in biological systems and their role in host defense, tissue damage, metabolic regulation and signaling, the identification of the endothelial-derived relaxing factor as the nitrogen monoxide radical (more commonly named nitric oxide) and its physiological and pathological implications. The article highlights the perception of hydrogen peroxide and other hydroperoxides as signaling molecules, which marks the beginning of the flourishing fields of redox regulation and redox signaling. Final comments describe the development of the redox language. In the 18th and 19th century, it was highly individualized and hard to translate into modern terminology. In the 20th century, the redox language co-developed with the chemical terminology and became clearer. More recently, the introduction and inflationary use of poorly defined terms has unfortunately impaired the understanding of redox events in biological systems.

[Function and physiology of the maxillary sinus]. / Funktion und Physiologie der Kieferhöhle.

BACKGROUND: The question of the "true" function of the maxillary sinus and the paranasal sinuses (PS) has been a controversial issue in the literature for decades, leading to many discussions and speculations. OBJECTIVE: This review briefly summarizes various theories on the possible physiology and functions of the maxillary sinus/PS that have been discussed over the centuries. MATERIALS AND METHODS: A literature search was conducted in PubMed using a combination of the search terms "physiology," "function," "maxillary sinus," and "paranasal sinuses." RESULTS: Current and scientifically evidenced theories are described. "Sinusology" is the science of the PS. The maxillary sinuses might simply serve to improve the respiratory function of the nose. A flow of inspiratory air does not occur. The maxillary sinuses are decisively involved in the production of nitrogen monoxide (NO) and thus in supporting the immune defense of the nasal cavity. The mucosa of the maxillary sinus continuously synthesizes NO and serves as a reservoir of NO. Other important functions are protection of the orbit and the brain in case of skull fractures, as well as weight reduction of the skull. CONCLUSION: The various theories about the function of the PS still raise many questions and their true function is yet not fully understood. Possible functions of the maxillary sinuses are local immune defense through the production of NO. The PS serve as a crumple zone for vital cerebral structures in the context of craniocerebral traumas.

Effect of Humidity on Light-Activated NO and NO2 Gas Sensing by Hybrid Materials.

Air humidity is one of the main factors affecting the characteristics of semiconductor gas sensors, especially at low measurement temperatures. In this work we analyzed the influence of relative humidity on sensor properties of the hybrid materials based on the nanocrystalline SnO2 and In2O3 and Ru (II) heterocyclic complex and verified the possibility of using such materials for NO (0.25-4.0 ppm) and NO2 (0.05-1.0 ppm) detection in high humidity conditions (relative humidity (RH) = 20%, 40%, 65%, 90%) at room temperature during periodic blue (λmax = 470 nm) illumination. To reveal the reasons for the different influence of humidity on the sensors' sensitivity when detecting NO and NO2, electron paramagnetic resonance (EPR) spectroscopy and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) investigations were undertaken. It was established that the substitution of adsorbed oxygen by water molecules causes the decrease in sensor response to NO in humid air. The influence of humidity on the interaction of sensitive materials with NO2 is determined by the following factors: the increase in charge carrier's concentration, the decrease in the number of active sites capable of interacting with gases, and possible substitution of chemisorbed oxygen with NO2- groups.