High Concentrations Of Nitric Oxide Research Articles

Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways

BackgroundIn the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive.MethodsLentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2’-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model.ResultsTrem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1β, and caused further DNA damage and promoted the apoptosis rate of tumor cells.ConclusionsOur findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.

Coumarin-Furoxan Hybrid Suppressed the Proliferation and Metastasis of Triple-Negative Breast Cancer by Activating Mitochondrial Stress and Cell Apoptosis.

Triple-negative breast cancer (TNBC) typically manifests as higher invasive carcinoma correlated with a worse prognosis that primarily relies on chemotherapy. There is growing evidence that nitric oxide (NO) donor drugs have the potential for anticancer therapy. On this basis, we constructed and evaluated a novel coumarin-furoxan hybrid 4A93 as an effective antitumor candidate drug. 4A93 exhibits low IC50 values in three TNBC cell lines and inhibits colony formation and DNA synthesis, probably due to the release of high concentrations of NO in mitochondria, which induces oxidative stress, mitochondrial dysfunction, and apoptosis. Further research suggests that 4A93 might destroy mitochondria by opening the mitochondrial permeability transition pore (mPTP), depolarizing the mitochondrial membrane potential (MMP), and promoting the release of cytochrome c into the cytoplasm. Intrinsic apoptosis is induced finally, along with Akt/Erk signaling suppression. Additionally, 4A93 underregulates the Epithelial-mesenchymal transition process to inhibit cell migration and invasion. In 4T1 subcutaneous and hematogenous models of mice, 4A93 therapy suppresses the tumor growth and prevented lung metastasis with favorable biosafety. Our results provide insights into 4A93 in TNBC treatment and validate the contribution of NO donors in tumor therapy.

Mitochondrial Targeted Thermosensitive Nanocarrier for Near-Infrared-Triggered Precise Synergetic Photothermal Nitric Oxide Chemotherapy.

Nitric oxide (NO) intervenes, that is, a potential treatment strategy, and has attracted wide attention in the field of tumor therapy. However, the therapeutic effect of NO is still poor, due to its short half-life and instability. Therapeutic concentration ranges of NO should be delivered to the target tissue sites, cell, and even subcellular organelles and to control NO generation. Mitochondria have been considered a major target in cancer therapy for their essential roles in cancer cell metabolism and apoptosis. In this study, mesoporous silicon-coated gold nanorods encapsulated with a mitochondria targeted and the thermosensitive lipid layer (AuNR@MSN-lipid-DOX) served as the carrier to load NO prodrug (BNN6) to build the near-infrared-triggered synergetic photothermal NO-chemotherapy platform (AuNR@MSN(BNN6)-lipid-DOX). The core of AuNR@MSN exhibited excellent photothermal conversion capability and high loading efficiency in terms of BNN6, reaching a high value of 220 mg/g (w/w), which achieved near-infrared-triggered precise release of NO. The outer biocompatible lipid layer, comprising thermosensitive phospholipid DPPC and mitochondrial-targeted DSPE-PEG2000-DOX, guided the whole nanoparticle to the mitochondria of 4T1 cells observed through confocal microscopy. In the mitochondria, the nanoparticles increased the local temperature over 42 °C under NIR irradiation, and a high NO concentration from BNN6 detected by the NO probe and DSPE-PEG2000-DOX significantly inhibited 4T1 cancer cells in vitro and in vivo under the synergetic photothermal therapy (PTT)-NO therapy-chemotherapy modes. The built NIR-triggered combination therapy nanoplatform can serve as a strategy for multimodal collaboration.

A coumarin-furoxan hybrid as novel nitric oxide donor induced cell apoptosis and ferroptosis in NSCLC by promoting S-nitrosylation of STAT3 and negative regulation of JAK2-STAT3 pathway

Non-small cell lung cancer (NSCLC) still lacks effective treatment because of its extensive mutation diversity and frequent drug resistance. Therefore, it is urgent to develop new therapeutic strategies for NSCLC. In this study, we evaluated the inhibitory effect of a new coumarin-furoxan hybrid compound 9, a nitric oxide (NO) donor drug, on NSCLC proliferation and its mechanism. Our results show that compound 9 can inhibit the growth of four NSCLC cell lines and H1975 xenograft model in a dose-dependent manner. Compound 9 effectively releases high concentrations of NO within the mitochondria, leading to cellular oxidative stress, mitochondrial dysfunction, and apoptosis. Moreover, compound 9 inhibits JAK2/STAT3 protein phosphorylation and induces S-nitrosylation modification of STAT3, ultimately resulting in endogenous apoptosis in NSCLC. Additionally, compound 9 significantly induces NSCLC ferroptosis by depleting intracellular GSH, elevating MDA levels, inhibiting SLC7A11/GSH protein expression, and negatively regulating the JAK2/STAT3 pathway. In summary, this study elucidates the inhibitory effects of compound 9 on NSCLC proliferation and provides insights into the underlying mechanisms, offering new possibilities for NSCLC treatment strategies.

Aqueous Electroreduction of Nitric Oxide to Ammonia at Low Concentration via Vacancy Engineered FeOCl

AbstractElectroreduction of nitric oxide (NO) to NH3 (NORR) has gained extensive attention for the sake of low carbon emission and air pollutant treatment. Unfortunately, NORR is greatly hindered by its sluggish kinetics, especially under low concentrations of NO. Herein, we developed a chlorine (Cl) vacancy strategy to overcome this limitation over FeOCl nanosheets (FeOCl‐VCl). Density functional theory (DFT) calculations revealed that the Cl vacancy resulted in defective Fe with sharp d‐states characteristics in FeOCl‐VCl to enhance the absorption and activation of NO. In situ X‐ray absorption near‐edge structure (XANES) and attenuated total reflection‐infrared spectroscopy (ATR‐IR) verified the lower average oxidation state of defective Fe to enhance the electron transfer for NO adsorption/activation and facilitate the generation of key NHO and NHx intermediates. As a result, the FeOCl‐VCl exhibited superior NORR activities with the NH3 Faradaic efficiency up to 91.1 % while maintaining a high NH3 yield rate of 455.4 μg cm−2 h−1 under 1.0 vol % NO concentration, competitive with those of previously reported literatures under higher NO concentration. Further, the assembled Zn‐NO battery utilizing FeOCl‐VCl as cathode delivered a record peak power density of 6.2 mW cm−2, offering a new route for simultaneous NO removal, NH3 production, and energy supply.

Aqueous Electroreduction of Nitric Oxide to Ammonia at Low Concentration via Vacancy Engineered FeOCl.

Electroreduction of nitric oxide (NO) to NH3 (NORR) has gained extensive attention for the sake of low carbon emission and air pollutant treatment. Unfortunately, NORR is greatly hindered by its sluggish kinetics, especially under low concentrations of NO. Herein, we developed a chlorine (Cl) vacancy strategy to overcome this limitation over FeOCl nanosheets (FeOCl-VCl ). Density functional theory (DFT) calculations revealed that the Cl vacancy resulted in defective Fe with sharp d-states characteristics in FeOCl-VCl to enhance the absorption and activation of NO. In situ X-ray absorption near-edge structure (XANES) and attenuated total reflection-infrared spectroscopy (ATR-IR) verified the lower average oxidation state of defective Fe to enhance the electron transfer for NO adsorption/activation and facilitate the generation of key NHO and NHx intermediates. As a result, the FeOCl-VCl exhibited superior NORR activities with the NH3 Faradaic efficiency up to 91.1 % while maintaining a high NH3 yield rate of 455.4 μg cm-2 h-1 under 1.0 vol % NO concentration, competitive with those of previously reported literatures under higher NO concentration. Further, the assembled Zn-NO battery utilizing FeOCl-VCl as cathode delivered a record peak power density of 6.2 mW cm-2 , offering a new route for simultaneous NO removal, NH3 production, and energy supply.

Endogenous Nitric Oxide Releases In Situ for RNS/ROS Synergistic Cancer Therapy

AbstractGas therapy, represented by nitric oxide (NO), has shown a powerful anti‐tumor effect. However, current NO therapy relies on NO precursors, which are often released prematurely during in vivo delivery, resulting in poor targeting and obvious toxic side effects. Herein, a core/shell‐structured nanocatalyst is designed and prepared to catalyze the generation of NO in tumor without introduction of NO donor. In this system, C‐Z@CM is prepared by coating the octahedron of Cu‐MOF with a nano‐ZnO, and camouflaging homologous tumor cell membrane. After the nanomedicine is taken up by tumor cells, ZnO reacts in situ with endogenous S‐nitrosoglutathione (GSNO), which is highly expressed in tumors, to continuously and stably generate NO. In addition, the dispersed copper ions in C‐Z@CM acts as the catalytic active centers of the Fenton‐like reaction, which catalyzes H2O2 to generate a large number of hydroxyl radicals (•OH). Importantly, the cascade of NO and reactive oxygen species (ROS) leads to the massive production of more lethal reactive nitrogen species (RNS), further enhancing the therapeutic effect. Catalytic production of high concentrations of NO in situ in the tumor, combined with the cascade generation of ROS and RNS, accompanied by glutathione (GSH) depletion, achieving effective tumor suppression.

The Effect of High Nitric Oxide Concentrations on Oxygenators in Cardiopulmonary Bypass Machines (Experimental Study)

The aim of the study. To study the effect of high nitric oxide concentrations on hollow polypropylene fibers of oxygenators.Materials and methods. The study was conducted in two stages. At the first stage, we evaluated the stability of oxygenator membrane made of hollow polypropylene fibers after six hours of exposure to air-oxygen mixture containing NO at 500 parts per million, or 500 pro pro mille (ppm) concentration, using mass spectrometry and infrared spectroscopy. At the second stage, an experiment with cardiopulmonary bypass (CPB) was conducted on 10 pigs. In the study group (n=5) animals sweep gas was supplied to the oxygenator as an air-oxygen mixture with NO at 100 ppm. In the control group animals (n=5) an air-oxygen mixture was used without NO. The CPB lasted for 4 hours, followed by observation for 12 hours. NO, NO2 (at the inlet and outlet of the oxygenator), and the dynamics of methemoglobin were evaluated. After weaning of animals from CPB, the oxygenators were tested for leakproofness, and scanning electron microscopy (SEM) was performed.Results. The oxygenator made of polypropylene hollow fibers retained its gas transfer parameters after six hours of exposure to air-oxygen mixture containing NO at 500 ppm. Based on IR-Fourier spectroscopy findings, NO did not affect structural integrity of polypropylene membranes. NO added to gas mixture at 100 ppm did not increase NO2 to toxic level of 2 ppm in 91% of control tests during 4 hours CPB in pigs; mean value was 1.58 ± 0.28 ppm. Methemoglobin concentration did not exceed the upper limit of permissible level (3%), and there were no statistically significant differences with the control group. All tested oxygenators have passed the leakproofness test. According to SEM findings, larger amounts of fibrin deposits were found in the control group oxygenators vs study group.Conclusion. There were no negative effects of NO at 500 ppm concentration on the oxygenator membrane made of hollow polypropylene fibers. NO at 100 ppm in a gas-mixture supplied to oxygenators did not lead to an exceedance of safe NO2 and methemoglobin concentrations in an animal model. Reduced fibrin deposits on hollow fibers of polypropylene oxygenator membranes were observed when with NO at a level of 100 ppm was added to a gas mixture.

Inhalable Nitric Oxide Delivery Systems for Pulmonary Arterial Hypertension Treatment.

Pulmonary arterial hypertension (PAH) is a severe medical condition characterized by elevated blood pressure in the pulmonary arteries. Nitric oxide (NO) is a gaseous signaling molecule with potent vasodilator effects; however, inhaled NO is limited in clinical practice because of the need for tracheal intubation and the toxicity of high NO concentrations. In this study, inhalable NO-releasing microspheres (NO inhalers) are fabricated to deliver nanomolar NO through a nebulizer. Two NO inhalers with distinct porous structures are prepared depending on the molecular weights of NO donors. It is confirmed that pore formation can be controlled by regulating the migration of water molecules from the external aqueous phase to the internal aqueous phase. Notably, open porous NO inhalers (OPNIs) can deliver NO deep into the lungs through a nebulizer. Furthermore, OPNIs exhibit vasodilatory and anti-inflammatory effects via sustained NO release. In conclusion, the findings suggest that OPNIs with highly porous structures have the potential to serve as tools for PAH treatment.

PolyQ-Expansion Causes Mitochondria Fragmentation Independent of Huntingtin and Is Distinct from Traumatic Brain Injury (TBI)/Mechanical Stress-Mediated Fragmentation Which Results from Cell Death.

Mitochondrial dysfunction has been reported in many Huntington's disease (HD) models; however, it is unclear how these defects occur. Here, we test the hypothesis that excess pathogenic huntingtin (HTT) impairs mitochondrial homeostasis, using Drosophila genetics and pharmacological inhibitors in HD and polyQ-expansion disease models and in a mechanical stress-induced traumatic brain injury (TBI) model. Expression of pathogenic HTT caused fragmented mitochondria compared to normal HTT, but HTT did not co-localize with mitochondria under normal or pathogenic conditions. Expression of pathogenic polyQ (127Q) alone or in the context of Machado Joseph Disease (MJD) caused fragmented mitochondria. While mitochondrial fragmentation was not dependent on the cellular location of polyQ accumulations, the expression of a chaperone protein, excess of mitofusin (MFN), or depletion of dynamin-related protein 1 (DRP1) rescued fragmentation. Intriguingly, a higher concentration of nitric oxide (NO) was observed in polyQ-expressing larval brains and inhibiting NO production rescued polyQ-mediated fragmented mitochondria, postulating that DRP1 nitrosylation could contribute to excess fission. Furthermore, while excess PI3K, which suppresses polyQ-induced cell death, did not rescue polyQ-mediated fragmentation, it did rescue fragmentation caused by mechanical stress/TBI. Together, our observations suggest that pathogenic polyQ alone is sufficient to cause DRP1-dependent mitochondrial fragmentation upstream of cell death, uncovering distinct physiological mechanisms for mitochondrial dysfunction in polyQ disease and mechanical stress.

Design, Synthesis, and Biological Evaluation of Esculetin-Furoxan-DEAC Ternary Hybrids for Anti-Triple Negative Breast Cancer.

Twelve new hybrid compounds of Esculetin with nitric oxide (NO) donors and/or mitochondrial targeting groups were designed, synthesized, and evaluated for their anti-tumor activity and mechanism in vitro and in vivo. Notably, the most potent compound A11 exhibited nanomolar antiproliferative activity on triple-negative breast cancer (TNBC) MDA-MB-231 cells (IC50 = 8 nM) with a strikingly selective inhibitory effect. The mechanism of A11 involves targeting MDA-MB-231 cells' mitochondria, releasing a high NO concentration, and increasing the expression of cyclophilin D (CypD), leading to increased reactive oxygen species (ROS) and triggering cancer cell apoptosis. Additionally, A11 could arrest the cell cycle at the G2/M phase to achieve anti-tumor effects. Moreover, A11 demonstrated a superior TNBC inhibition rate and diminished toxicity relative to doxorubicin (DOX) in vivo. In summary, A11 serves as a noteworthy contender for TNBC treatment with high potency and minimal toxicity.

Nitric oxide: an old drug but with new horizons in ophthalmology-a narrative review.

Based on basic knowledge and prior research on nitric oxide (NO), the potential of NO for treating eye diseases is reviewed, and the possibility of NO-based eye drops in clinical practice and the future potential of NO in ophthalmology are discussed. A PubMed search was performed for English-language original reports and reviews using the following key words: nitric oxide, eye, ocular, and drug. NO is synthesized in the human body by NO synthase (NOS) from L-arginine or through enzyme-dependent reduction of dietary nitrate. Three types of NOS (eNOS, nNOS, and iNOS) are abundantly expressed in the eye under normal physiologic or pathologic conditions. The biological effect of NO in the eye is dose dependent. Low intraocular NO concentrations, produced by eNOS or nNOS, have various cellular effects, including vasodilation, intraocular pressure (IOP) regulation, and neuroprotection. iNOS induced under pathologic ocular conditions produces high NO concentrations in the local environment and mediates tissue inflammation, ocular cell apoptosis, and neurodegeneration. In particular, increased iNOS has been reported in glaucoma and retinal ischemic or degenerative diseases. NO plays a vital role in ocular injury. NO can facilitate ocular surface wound healing while eradicating pathogens such as bacteria and Acanthamoeba in chemical burns or infectious keratitis. Furthermore, NO has antifibrotic activity via the cyclic guanosine monophosphate (cGMP) signaling pathway. NO causes smooth muscle relaxation, which can be used to inhibit myopia progression in children. NO can be a stem cell modulator and may help in treating ocular stem cell disorders. Because of its diverse biologic effects, NO can be a key player in regulating ocular inflammation in various ocular diseases, aiding ocular surface wound healing, controlling IOP in glaucoma, alleviating retinal disease, and suppressing myopia progression. Although there remain limitations to the effective use of highly unstable state, gaseous NO, the role of NO in the field of ophthalmology can be greatly expanded through the development of novel NO donors and effective delivery platforms.

The current scenario of furoxan hybrids with anticancer potential

AbstractCancer is one of the most common and deadliest diseases affecting millions of human beings globally. Treatment of cancer has achieved great advancements, and chemotherapy remains one of the most important means. However, the chemotherapy suffers from apparent limitations including drug resistance, systemic toxicity, adverse effects, and tumor recurrence, creating an urgent demand to develop novel anticancer chemotherapeutics. Furoxan derivatives could exert anticancer activity via releasing high concentrations of nitric oxide (NO), which could induce cellular apoptosis, arrest cell cycle, inhibit the migration and invasion of cells, and suppress angiogenesis. Hence, furoxan derivatives demonstrated potent in vitro and in vivo anticancer efficiency. In particular, furoxan hybrids, combination of other anticancer pharmacophores with furoxan moiety, demonstrated significant therapeutic effects on various cancers including drug‐resistant forms since these derivatives could act on multiple targets in cancer cells simultaneously. Accordingly, furoxan hybrids constitute an important source in the development of novel chemotherapeutic agents with anticancer activity. This review is to highlight the current scenario of furoxan hybrids with anticancer potential, covering articles published from 2012 to present. The structure–activity relationships and mechanisms of action are discussed to continuously open up a map for the remarkable exploration of more effective candidates.

Removal of NO at low concentrations from polluted air in semi-closed environments by activated biochars from renewables feedstocks

Efficient measures are urgently required in large cities for nitric oxide (NO) elimination from air in urban semi-closed environments (parking lots and tunnels), characterized by low NO concentrations (<10 ppmv) and temperatures. One of the most promising abatement alternatives is the NO oxidation to NO2, which can be further easily captured in an alkali solution or over a porous solid. However, most of the research devoted to this topic is focused on the elimination of NO from fuel exhaust gases, with high NO concentrations (400–2000 ppmv). In this work, sustainable and low-cost activated biochars of different origin and having very different ash contents were employed in NO removal at very low concentrations. Thus, low ash content forestry (oak woodchips, OAK) and high ash content from agriculture (oilseed rape straw, OSR) biochars were subjected to physical activation with CO2 at 900 °C (OAK550-A900CO2 and OSR700-A900CO2, respectively). The NO removal performance tests of such activated carbons were carried out at different experimental conditions: i.e., temperature, relative humidity (0–50 vol% RH), NO-containing gas (N2 or air), amount of activated carbon, and NO concentration, to assess how the activated biochar properties influence their NO removal capacity. The sample OSR700-A900CO2 contained a higher population of oxygen surface functionalities, which might play an important role in the NO removal efficiency in dry conditions since they could assist NO oxidation on carbon active sites when used above room temperature (50–75 °C). However, at room temperature (25 °C), the presence of narrow micropore size distribution at 6 Å became a more relevant property, since it facilitates an intimate contact between NO and O2. Accordingly, the activated biochar from OAK was much more efficient, achieving complete removal of NO from air flow (dry or with 50 vol% RH) at 25 °C during 400 min of testing, making it an ideal candidate as biofilter for purifying air streams of semi-closed spaces contaminated with low concentrations of NO.

Thermoacoustic Imaging-Guided Thermo-Chemotherapy for Hepatocellular Carcinoma Sensitized by a Microwave-Responsive Nitric Oxide Nanogenerator.

Imaging-guided percutaneous microwave thermotherapy has been regarded as an important alternative nonsurgical therapeutic strategy for hepatocellular carcinoma (HCC) that provides excellent local tumor control and favorable survival benefit. However, providing a high-resolution, real-time, and noninvasive imaging technique for intraoperative guidance and controlling postoperative residual tumor recurrence are urgent needs for the clinical setting. In this study, a cisplatin (CDDP)-loaded nanocapsule (NPs@CDDP) with microwave responsive property was prepared to simultaneously serve as a contrast agent of emerging thermoacoustic imaging and a sensitizing agent of microwave thermo-chemotherapy. Accompanying the enzymolysis in the tumor microenvironment, the NPs@CDDP responsively release l-arginine (l-Arg) and CDDP. l-Arg with excellent microwave-absorbing property allowed it to serve as a thermoacoustic imaging contrast agent for accurately delineating the tumor and remarkably increasing tumor temperature under ultralow power microwave irradiation. Apart from the chemotherapeutic effect, CDDP elevated the intracellular H2O2 level through cascade reactions and further accelerated the continuous transformation of l-Arg to nitric oxide (NO), which endowed the NPs@CDDP with NO-generation capability. Notably, the high concentration of intracellular NO was proved to aggravate lipid peroxidation and greatly improved the efficacy of microwave thermo-chemotherapy. Thereby, NPs@CDDP was expected to serve as a theranostic agent integrating the functions of tumor microenvironment-responsive drug delivery system, contrast agent of thermoacoustic imaging, thermal sensitizing agent, and NO nanogenerator, which was promising to provide a potential imaging-guided therapeutic strategy for HCC.

Inducible Nitric Oxide Synthase Embedded in Alginate/Polyethyleneimine Hydrogel as a New Platform to Explore NO-Driven Modulation of Biological Function.

Nitric oxide (NO), a small free radical molecule, turned out to be pervasive in biology and was shown to have a substantial influence on a range of biological activities, including cell growth and apoptosis. This molecule is involved in signaling and affects a number of physiologic functions. In recent decades, several processes related to cancer, such as angiogenesis, programmed cell death, infiltration, cell cycle progression, and metastasis, have been linked with nitric oxide. In addition, other parallel work showed that NO also has the potential to operate as an anti-cancer agent. As a result, it has gained attention in cancer-related therapeutics. The nitric oxide synthase enzyme family (NOS) is required for the biosynthesis of nitric oxide. It is becoming increasingly popular to develop NO-releasing materials as strong tumoricidal therapies that can deliver sustained high concentrations of nitric oxide to tumor sites. In this paper, we developed NO-releasing materials based on sodium alginate hydrogel. In this regard, alginate hydrogel discs were modified by adsorbing layers of polyethyleneimine and iNOS-oxygenase. These NO-releasing hydrogel discs were prepared using the layer-by-layer film building technique. The iNOS-oxygenase is adsorbed on the positively charged polyethyleneimine (PEI) matrix layer, which was formed on a negatively charged sodium alginate hydrogel. We show that nitric oxide is produced by enzymes contained within the hydrogel material when it is exposed to a solution containing all the components necessary for the NOS reaction. The electrostatic chemical adsorption of the layer-by-layer process was confirmed by FTIR measurements as well as scanning electron microscopy. We then tested the biocompatibility of the resulting modified sodium alginate hydrogel discs. We showed that this NOS-PEI-modified hydrogel is overall compatible with cell growth. We characterized the NOS/hydrogel films and examined their functional features in terms of NO release profiles. However, during the first 24 h of activity, these films show an increase in NO release flux, followed by a gradual drop and then a period of stable NO release. These findings show the inherent potential of using this system as a platform for NO-driven modulation of biological functions, including carcinogenesis.

Nitric oxide and Nitrous oxide accumulation, oxygen production during nitrite denitrification in an anaerobic/anoxic sequencing batch reactor: exploring characteristics and mechanism.

Nitrite denitrification has received increasing attention due to its high efficiency, low energy consumption, and sludge yield. However, the nitric oxide (NO) and nitrous oxide (N2O) which are harmful to the environment, microorganisms, and humans are produced in this process. In order to mitigate NO and N2O production, the biological mechanisms of NO and N2O accumulation, as well as NO detoxification during nitrite denitrification in a sequencing batch reactor were studied. Results showed that the peak of NO accumulation increased from 0.29 [Formula: see text] 0.01 to 3.12 [Formula: see text] 0.34mg L-1 with the increase of carbon to nitrogen ratio (COD/N), which is caused by the sufficient electron donor supply for NO2--N reduction process at high COD/N. Furthermore, the result suggested that NO accumulation with no pH adjustment was 12 times higher than that with pH adjustment. It is related to the inhibition on NO reductase caused by the high free nitrous acid (FNA) and NO concentration with no pH adjustment. The pathways of NO detoxification included NO emission, reduction, and dismutation, and the more NO produced, the high proportion of NO dismutation pathway. Result showed that the maximum of oxygen production during NO dismutation reached to 1.39mg L-1. N2O accumulation was mainly associated with FNA and NO inhibition, COD/N. The peak of N2O accumulation presented a completely opposite trend at pH adjustment and no pH adjustment, it is because that the higher FNA and NO concentration at high COD/N without pH adjustment will inhibit the N2O reductase activity, resulting in the N2O reduction was hindered during nitrite denitrification.

Curcumin-Added Whey Protein Positively Modulates Skeletal Muscle Inflammation and Oxidative Damage after Exhaustive Exercise.

(1) Background: Exhaustive exercise can induce muscle damage. The consumption of nutritional compounds with the ability to positively influence the oxidative balance and an exacerbated inflammatory process has been previously studied. However, little is known about the nutritional value of curcumin (CCM) when mixed with whey protein concentrate (WPC). This study was developed to evaluate the effect of CCM-added WPC on inflammatory and oxidative process control and histopathological consequences in muscle tissue submitted to an exhaustive swimming test (ET). (2) Methods: 48 animals were randomly allocated to six groups (n = 8). An ET was performed 4 weeks after the start of the diet and animals were euthanized 24 h post ET. (3) Results: WPC + CCM and CCM groups reduced IL-6 and increased IL-10 expression in muscle tissue. CCM reduced carbonyl protein after ET compared to standard AIN-93M ET and WPC + CCM ET diets. Higher nitric oxide concentrations were observed in animals that consumed WPC + CCM and CCM. Consumption of WPC + CCM or isolated CCM reduced areas of inflammatory infiltrate and fibrotic tissue in the muscle. (4) Conclusions: WPC + CCM and isolated CCM contribute to the reduction in inflammation and oxidative damage caused by the exhaustive swimming test.

The metabolic phenotype of the patient influences the reduction in carotid intima-media thickness achieved following metabolic surgery.

To determine whether metabolic phenotype is associated with the change in carotid intima-media thickness (CIMT) in patients undergoing bariatric /metabolic surgery (BMS). We performed a case-control study of BMS candidates who had metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO). We measured the change in CIMT during the 9 months following BMS. The plasma tumor necrosis factor-α, interleukin-1β, adiponectin, leptin, nitric oxide (NO), vascular endothelial growth factor A (VEGF-A), and malondialdehyde concentrations were determined, adipocyte area was measured histologically, and adipose tissue area was estimated using computed tomography. Fifty-six patients (mean age 44.5 years, mean body mass index 44.9 kg/m2, 53% women, and 53% had MUO) were studied. Nine months following BMS, the MUO phenotype was not associated with a significant reduction in CIMT, and that of the MHO group was larger. In addition, fewer participants achieved a 10% reduction in CIMT in the MUO group. A CIMT reduction was associated with lower VEGF-A and NO in the MUO group, while that in the MHO group was associated with a higher NO concentration. The metabolic phenotype of patients may influence their change in CIMT following BMS, probably through circulating vasodilatory and pro-inflammatory molecules.

Simultaneous detection of three chemical species (NO, O, O2) using a single broadband femtosecond laser

Simultaneous nitric oxide (NO) laser-induced fluorescence (LIF), atomic oxygen (O) two-photon LIF (TPLIF), and molecular oxygen (O2) LIF were demonstrated using a single broadband femtosecond (fs) laser in methane- and hydrogen-fueled flames. An amplified Ti:Sapphire laser with ∼80-fs pulse duration was used to pump an optical parametric amplifier (OPA) to generate 226.1-nm pulses having 2.3 nm (∼450 cm−1) bandwidth to excite all three species simultaneously. The specific excitation transitions are NO A-X (0,0) system, O 3p3P←←2p3P two-photon transition, and O2B3Σu−−X3Σg− Schumann-Runge system. Detailed emission characterization was performed using a 1D imaging spectrometer to identify suitable emission bands for interference-free detection of each species. A simultaneous detection system consisting of a visible and a UV camera provided the optimal detection of all three species. Imaging studies revealed high concentrations of NO, O, and O2 at the edge of the flame cone of Bunsen flames because NO and O are produced at the hot flame front. O2 LIF signal was present only at the flame front because of the strong temperature dependence of the O2 Schumann-Runge system. Direct imaging of O TPLIF enabled single-shot as well as high-fidelity shot-averaged line images in stable laminar flames. Equivalence ratio scans in the CH4/air Hencken flames showed good agreements for O and O2 with Cantera equilibrium predictions performed using GRI-Mech 3.0. Although the NO measurements deviated from the equilibrium calculations on the fuel-rich side, it agreed well with previously reported NO LIF measurements in a similar flame. This discrepancy is likely due to Prompt NO, which was not considered in the simulation. NO LIF measurements as a function of height-above-the-burner in the H2/air Hencken flames agreed well with calculated NO mole fractions using the UNICORN flame code. The present study lays the foundation for single-laser imaging of three critical flame species in NO formation pathways in combustion systems.