Large Amounts Of Nitric Oxide Research Articles

Trident-inspired fucoidan-based armor-piercing microcapsule for programmed acute pulmonary embolism treatment

Pulmonary embolism remains the third leading cause of human mortality after malignant tumors and myocardial infarction. Commonly available thrombolytic therapeutic agents suffer from the limitations of very short half-life, inadequate targeting, limited clot penetration, and a propensity for severe bleeding. Inspired by the trident, we developed the armor-piercing microcapsule (MC), fucoidan-urokinase-S-nitrosoglutathione-polydopamine@MC (FUGP@MC), which exhibited a triple combination of photothermal, mechanical and pharmacological thrombolysis for the therapeutic treatment of acute pulmonary embolism (APE). Briefly, the outermost fucoidan layer was utilized for targeting to the APE area. Programmed APE treatment was triggered by near-infrared (NIR) light irradiation. Photothermal thrombolytic therapy was carried out by photothermal conversion of polydopamine. The photothermal conversion broke the S-nitroso bond in S-nitrosoglutathione (GSNO) and produced large amounts of nitric oxide (NO) for mechanical thrombolysis, which subsequently disrupted the interfacial structure of microcapsule to stimulate the release of the urokinase (UK), leading to a triple synergistic thrombolytic effect. The results demonstrated that the embolization residual rate of FUGP@MC (contained ≈ 1452.5 IU/kg UK) group was significantly lower than that of UK (10,000 IU/kg) group (6.35 % VS 16.78 %). Remarkably, FUGP@MC demonstrated a reliable in vivo biosafety proficiency. In summary, trident-inspired armor-piercing microcapsule FUGP@MC reveals a potential avenue for advancing pulmonary embolism therapeutics and promises to be a safer alternative candidate to current drug approaches.

Antrodia cinnamomea extract alleviates bleomycin-induced pulmonary fibrosis in mice by inhibiting the mTOR pathway

BackgroundPulmonary fibrosis is a progressive diffuse parenchymal lung disorder with a high mortality rate. Studies have indicated that injured lung tissues release various pro-inflammatory factors, and produce a large amount of nitric oxide. There is also accumulation of collagen and oxidative stress-induced injury, collectively leading to pulmonary fibrosis. Antrodia cinnamomea is an endemic fungal growth in Taiwan, and its fermented extracts exert anti-inflammatory effects to alleviate liver damages. Hence, we hypothesized and tested the feasibility of using A. cinnamomea extracts for treatment of pulmonary fibrosis. MethodsThe TGF-β1-induced human lung fibroblast cells (MRC-5) in vitro cell assay were used to evaluate the effects of A. cinnamomea extracts on the collagen production in MRC-5. Eight-week-old ICR mice were intratracheally administered bleomycin and then fed with an A. cinnamomea extract on day 3 post-administration of bleomycin. At day 21 post-bleomycin administration, the pulmonary functional test, the expression level of inflammation- and fibrosis-related genes in the lung tissue, and the histopathological change were examined. ResultsThe A. cinnamomea extract significantly attenuated the expression level of collagen in the TGF-β1-induced MRC-5 cells. In the A. cinnamome-treated bleomycin-induced lung fibrotic mice, the bodyweight increased, pulmonary functions improved, the lung tissues expression level of inflammatory factor and the fibrotic indicator were decreased, and the histopathological results showed the reduction of thickening of the inter-alveolar septa. ConclusionsThe Antrodia cinnamomea extract significant protects mice against bleomycin-induced lung injuries through improvement of body weight gain and lung functions, and attenuation of expression of inflammatory and fibrotic indicators.

Biomimetic Antithrombotic Tissue-Engineered Vascular Grafts for Converting Cholesterol and Free Radicals into Nitric Oxide.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) are essential materials used in bypass or replacement surgery for cardiovascular diseases; however, their application efficacy is limited because of patency rates, especially under hyperlipidemia, which is also clinically observed in patients with cardiovascular diseases. In such cases, improving sdTEVG patency is challenging because cholesterol crystals easily cause thrombosis and impede endothelialization. Here, the development of a biomimetic antithrombotic sdTEVG incorporating cholesterol oxidase and arginine into biomineralized collagen-gold hydrogels on a sdTEVG surface is described. Biomimetic antithrombotic sdTEVGs represent a multifunctional substrate for the green utilization of hazardous substances and can convert cholesterol into hydrogen peroxide, which can react with arginine to generate nitric oxide (NO). NO is a vasodilator that can simulate the antithrombotic action of endothelial cells under hyperlipidemic conditions. In vivo studies show that sdTEVGs can rapidly produce large amounts of NO via a cholesterol catalytic cascade to inhibit platelet aggregation, thereby improving the blood flow velocity and patency rates 60 days after sdTEVG transplantation. A practical and reliable strategy for transforming "harmful" substances into "beneficial" factors at early transplantation stages is presented, which can also promote vascular transplantation in patients with hyperlipidemia.

Intracellular behavior of Nocardia seriolae and its apoptotic effect on RAW264.7 macrophages.

Nocardia seriolae, an intracellular gram-positive pathogen, is prone to infecting immunocompromised and surface-damaged fish, causing serious losses to the aquaculture industry. Although a previous study has demonstrated that N. seriolae infects macrophages, the persistence of this bacterium in macrophages has not been well characterized. To address this gap, we used the macrophage cell line RAW264.7, to investigate the interactions between N. seriolae and macrophages and deciphered the intracellular survival mechanism of N. seriolae. Confocal and light microscopy revealed that N. seriolae entered macrophages 2 hours post-inoculation (hpi), were phagocytosed by macrophages at 4-8 hpi, and induced the formation of multinucleated macrophages by severe fusion at 12 hpi. Flow cytometry, evaluation of mitochondrial membrane potential, release of lactate dehydrogenase, and observation of the ultrastructure of macrophages revealed that apoptosis was induced in the early infection stage and inhibited in the middle and later periods of infection. Additionally, the expression of Bcl-2, Bax, Cyto-C, Caspase-3, Capase-8, and Caspase-9 was induced at 4 hpi, and then decreased at 6-8 hpi, illustrating that N. seriolae infection induces the activation of extrinsic and intrinsic apoptotic pathways in macrophages, followed by the inhibition of apoptosis to survive inside the cells. Furthermore, N. seriolae inhibits the production of reactive oxygen species and releases large amounts of nitric oxide, which persists in macrophages during infection. The present study provides the first comprehensive insight into the intracellular behavior of N. seriolae and its apoptotic effect on macrophages and may be important for understanding the pathogenicity of fish nocardiosis.

NO released via both a Cu-MOF-based donor and surface-catalyzed generation enhances anticoagulation and antibacterial surface effects.

The anticoagulation and antibacterial functions of implant and interventional catheters during indwelling will determine their success or failure. Here, an amino-containing copper-based metal-organic framework (Cu-MOF) coating was prepared on the thermoplastic polyurethane substrate (TPU) surface by spin coating for anti-thrombotic and anti-infection effects. The adhesion properties of the polyurethane prepolymer coating (PC) enhanced the binding force of Cu-MOF particles and TPU surface and improved stability. Due to the coordination affinity of Cu2+ with nitric oxide (NO) and the NO loading capacity of the amino group, it showed that a large amount of NO was loaded in the coating. Meanwhile, the coordinated Cu2+ in the coating also catalyzed endogenous NO donors to generate NO, which prolonged the NO release for up to 30 days. The results of antibacterial experiments showed that the NO released from the coating had good antibacterial effects on both E. coli and S. epidermidis. An obvious antibacterial ring can be seen and the antibacterial rate was higher than 96%. It also showed inhibiting platelet adhesion and activation, prolonged in vitro clotting time and inhibited thrombus formation. In summary, for the first time, NO release from the coating was realized by the combined ways of NO donor and catalytic endogenous NO donor. It can not only meet the high NO release rate required for early anticoagulation and antibacterial of the catheter but also maintain normal anticoagulation requirements in the later period.

Quantitative laser-induced fluorescence of NO in ammonia-hydrogen-nitrogen turbulent jet flames at elevated pressure

Ammonia is a very promising carbon-free fuel, but its combustion is prone to generate a large amount of harmful nitric oxide (NO). Designing NO reduction strategies for ammonia flames requires computational fluid dynamics and accurate kinetic mechanisms. However, there are currently no available experimental data that can be used to validate models describing chemistry-turbulence interactions in ammonia flames. This study introduces two non-premixed turbulent jet flames that emulate some features of the cracked ammonia combustion at 5 bar, relevant to micro gas turbines. These ammonia-hydrogen-nitrogen jet flames feature well-controlled boundary conditions and are particularly amenable to modeling. A one-dimensional NO laser-induced fluorescence (NO-LIF) method was implemented and combined with 1-D Raman spectroscopy to measure the NO mole fraction quantitatively. To avoid laser absorption by ammonia, excitation in the A2Σ+−X2Π (0–1) band near 236 nm was chosen instead of the more conventional (0–0) band near 226 nm. Due to the unsteady nature of turbulent jet flames, offline NO-LIF measurements are not useful, and undesirable interferences from Rayleigh scattering and oxygen LIF were instead quantified and removed using the temperature and major species mole fractions measured with Raman spectroscopy. NO quantification algorithms were optimized and validated first with a laminar NH3–H2–N2 counterflow flame, and then applied to the turbulent jet flames. Results show that a large amount of NO (∼1500 ppm) is produced in the NH3–H2–N2 jet flames. Increasing the ammonia cracking ratio from 14% to 28% reduces the NO concentration in laminar and turbulent NH3–H2–N2 flames. Data also shows that turbulence smear effects of differential diffusion. To the best of our knowledge, this is the first available database featuring quantitative measurements of spatially-resolved NO mole fraction in turbulent NH3–H2–N2 flames at a practically-relevant pressure. This unique database can be used in the future to validate turbulent combustion models for such flames.

Supramolecular Nitric Oxide Depot for Hypoxic Tumor Vessel Normalization and Radiosensitization.

In cancer radiotherapy, the lack of fixed DNAdamage by oxygen in hypoxic microenvironment of solid tumors often leads to severe radioresistance. Nitric oxide (NO) is a potent radiosensitizer that acts in two ways. It can directly react with the radical DNA thus fixing the damage. It also normalizes the abnormal tumor vessels, thereby increasing blood perfusion and oxygen supply. To achieve these functions, the dosage and duration of NO treatment need to be carefully controlled, otherwise it will lead to the exact opposite outcomes. However, a delivery method that fulfills both requirements is still lacking. A NO depot is designed for the control of NO releasing both over quantity and duration for hypoxic tumor vessel normalization and radiosensitization. In B16-tumor-bearing mice, the depot can provide low dosage NO continuously and release large amount of NO immediately before irradiation for a short period of time. These two modes of treatment work in synergy to reverse the radioresistance of B16tumors more efficiently than releasing at single dosage.

Nitric oxide as an indicator for assessing the resistance and susceptibility of cattle to leukemia

Abstract. The role of allelic variability of inducible nitric oxide synthase (iNOS) is significant in the study of the resistance and susceptibility of animals to leukemia infection. After analyzing the literature data, it can be stated that in the iNOS gene, allele A (with genotype AA) is responsible for resistance to the leukemia virus, and allele B (with genotype BB) is responsible for susceptibility. This is due to the frequency of occurrence of alleles and their genotypes of the polymorphic marker AN13-1 of the inducibeal nitric oxide synthase gene. The iNOS gene is capable of producing a large amount of nitric oxide, compared to other isoforms. In turn, nitric oxide causes death or can stop the growth of pathogenic microorganisms, including viruses. The purpose of this work is to further study nitric oxide as an indicator for determining the resistance and susceptibility of animals to leukemia, as well as the selection of specific primers for PCR-PDRF used in genotyping. Methods. The iNOS gene sequence was analyzed and a pair of specific primers were selected and synthesized using the Vector NTI program. Scientific novelty of this work lies in the fact that we have selected specific primers that are important for the analysis of cattle genotyping by allelic variants of the polymorphic marker AH13-1 of the iNOS gene. Results. Based on this work, a pair of primers iNOSF_new and iNOSR_new, with a calculated annealing temperature of 52 °C, were selected and synthesized, giving an amplicon with a length of 186 bp. The amplicon contains a polymorphic site that distinguishes the A and B alleles. During PCR-RFLP, the following genotype-specific fragments are formed: AA-47/139 bp; AB -186/139/47 bp; BB-186 bp.

Nitrosative Stress and Human Disease: Therapeutic Potential of Denitrosylation.

Proteins dynamically contribute towards maintaining cellular homeostasis. Posttranslational modification regulates the function of target proteins through their immediate activation, sudden inhibition, or permanent degradation. Among numerous protein modifications, protein nitrosation and its functional relevance have emerged. Nitrosation generally initiates nitric oxide (NO) production in association with NO synthase. NO is conjugated to free thiol in the cysteine side chain (S-nitrosylation) and is propagated via the transnitrosylation mechanism. S-nitrosylation is a signaling pathway frequently involved in physiologic regulation. NO forms peroxynitrite in excessive oxidation conditions and induces tyrosine nitration, which is quite stable and is considered irreversible. Two main reducing systems are attributed to denitrosylation: glutathione and thioredoxin (TRX). Glutathione captures NO from S-nitrosylated protein and forms S-nitrosoglutathione (GSNO). The intracellular reducing system catalyzes GSNO into GSH again. TRX can remove NO-like glutathione and break down the disulfide bridge. Although NO is usually beneficial in the basal context, cumulative stress from chronic inflammation or oxidative insult produces a large amount of NO, which induces atypical protein nitrosation. Herein, we (1) provide a brief introduction to the nitrosation and denitrosylation processes, (2) discuss nitrosation-associated human diseases, and (3) discuss a possible denitrosylation strategy and its therapeutic applications.

Near-infrared light triggered multi-mode synergetic therapy for improving antibacterial and osteogenic activity of titanium implants

Reducing bacterial infection and improving osseointegration are critical for the long-term use of orthopedic implants, especially for the infection related surgery. Here, mesoporous dopamine (MPDA) nanoparticles were loaded with nitric oxide (NO) donor, S-nitrosoglutathione (GSNO), and they were immobilized on the surface of titanium (Ti). When bacterial infections occurred, a large amount of NO was rapidly released and triggered by the thermal effect of MPDA after the near-infrared (NIR) light irradiation, which could damage the permeability and integrity of the bacterial membrane, leading to the leakage of bacterial DNA, proteins and ATP. Thus, bacteria was synergistically eliminated by NO and photothermal therapy (PTT) under NIR irradiation. While without NIR irradiation, the low concentration of NO was slowly released into the environment from GSNO, which promoted the proliferation and differentiation of osteoblasts. In addition, the in vivo results also demonstrated good osteogenic and antibacterial effects. Therefore, this study demonstrated a multi-mode synergetic therapy for promoting the antibacterial property and osseointegration of titanium implants.

Hispidin inhibits LPS-induced nitric oxide production in BV-2 microglial cells via ROS-dependent MAPK signaling.

Neuroinflammation is associated with many neurodegenerative diseases. Abnormal activation of microglial cells in the central nervous system (CNS) is a major characteristic of neuroinflammation. Nitric oxide (NO) free radicals are produced by activated microglia and prolonged presence of large quantities of NO in the CNS can lead to neuroinflammation and disease. Hispidin is a polyphenol derived from Phellinus linteus (a valuable medicinal mushroom) with strong antioxidant, anticancer and antidiabetic properties. A previous study demonstrated that hispidin significantly inhibited NO production via lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Therefore, the present study used MTT assay was used to detect the effect of hispdin on cell viability. Griess reagent analysis was used to measure NO production. Reverse transcription-semi quantitative PCR and western blotting were used to evaluate the effects of hispdin on iNOS mRNA and MAPK/ERK/JNK protein levels. Fluorescence microscopy and flow cytometry were used to detect the effects of hispdin on the production of ROS and phagocytosis of cells. The present results indicated that hispidin could significantly inhibit the increase of NO production and iNOS expression in BV-2 microglial cells stimulated by LPS. The inhibitory effect of hispidin on NO production was similar to that of S-methylisothiourea sulfate, an iNOS inhibitor. Signaling studies demonstrated that hispidin markedly suppresses LPS-induced mitogen activated protein kinases and JAK1/STAT3 activation, although not the NF-κB signaling pathway. The present observations in LPS-stimulated BV-2 microglial cells indicated that hispidin might serve as a therapeutic candidate for the treatment of NO-induced neuroinflammation and, potentially, as a novel iNOS inhibitor.

Nitric oxide modulation in neuroinflammation and the role of mesenchymal stem cells.

Nitric oxide is a versatile mediator formed by enzymes called nitric oxide synthases. It has numerous homeostatic functions and important roles in inflammation. Within the inflamed brain, microglia and astrocytes produce large amounts of nitric oxide during inflammation. Excessive nitric oxide causes neuronal toxicity and death and mesenchymal stem cells can be used as an approach to limit the neuronal damage caused by neuroinflammation. Mesenchymal stem cell therapy ameliorates inflammation and neuronal damage in disease models of Alzheimer's disease, Parkinson's disease, and other neuroinflammatory disorders. Interestingly, we have reported that in vitro, mesenchymal stem cells themselves contribute to a rise in nitric oxide levels through microglial cues. This may be an undesirable effect and highlights a possible need to explore acellular approaches for mesenchymal stem cell therapy in the central nervous system.

The role of nitric oxide in peptic ulcer: a narrative review.

Peptic ulcer refers to the inflammatory response and necrotic lesions of the mucosa under the action of various pathogenic factors, which goes deeply into the mucosal muscle layer and often occurs to the gastrointestinal mucosa related to gastric acid secretion, among which the stomach and duodenum are the most common. The clinical manifestations include slow onset, prolonged course and weekly upper abdominal pain. Nitric oxide (NO) is an intracellular and intercellular signaling molecule that plays an important role in many physiological and pathological processes. Studies have found that a small amount of NO produced in vivo plays a role in many physiological homeostasis, such as regulating blood pressure, platelet aggregation, nitrogenization of hemoglobin, and regulating proliferation and differentiation of stem cells. However, under the action of some cytokines and oxidative stress, intracellular NO synthase will catalyze the synthesis of large amounts of NO and participate in the inflammatory response, causing beneficial or harmful effect on the body. Numerous basic studies have focused on the relationship between NO and peptic ulcer. The purpose of this review is to summarize the role of NO in peptic ulcer and its possible mechanism.

Tetrazine-mediated bioorthogonal removal of 3-isocyanopropyl groups enables the controlled release of nitric oxide in vivo.

Bond cleavage bioorthogonal chemistry has been widely employed to restore or activate proteins or prodrugs. Nitric oxide (NO), as a free radical molecule, has joined the clinical arena of cancer therapy, since high levels of NO could produce a cancer cell growth inhibitory effect. However, the spatiotemporal controlled release of NO remains a great challenge, and bioorthogonal chemistry may open a new window. Herein, we described a class of O2-3-isocyanopropyl diazeniumdiolates 3a-f as new bioorthogonal NO precursors, which can be effectively uncaged via tetrazine-mediated bond cleavage reactions to liberate NO and acrolein in living cancer cells, exhibiting potent antiproliferative activity. Furthermore, 3a and tetrazine BTZ were respectively encapsulated into two liposomes. It was found that simultaneous administrations of the two liposomes could specifically release large amounts of NO in the implanted cancer cells in zebrafish, thus generating potent tumor suppression activity in vivo. Our findings indicate that the TZ-labile NO precursors could serve to expand the NO-based smart therapeutics and the scope of bioorthogonal chemistry utility in vivo in the near future.

An official JRS statement: The principles of fractional exhaled nitric oxide (FeNO) measurement and interpretation of the results in clinical practice

Nitric oxide (NO) is produced in the body and has been shown to have diverse actions in the abundance of research that has been performed on it since the 1970s, leading to Furchgott, Murad, and Ignarro receiving the Nobel Prize in Physiology or Medicine in 1998. NO is produced by nitric oxide synthase (NOS). NOS is broadly distributed, being found in the nerves, blood vessels, airway epithelium, and inflammatory cells. In asthma, inflammatory cytokines induce NOS activity in the airway epithelium and inflammatory cells, producing large amounts of NO. Measurement of fractional exhaled nitric oxide (FeNO) is a simple, safe, and quantitative method of assessing airway inflammation. The FeNO measurement method has been standardized and, in recent years, this noninvasive test has been broadly used to support the diagnosis of asthma, monitor airway inflammation, and detect asthma overlap in chronic obstructive pulmonary disease (COPD) patients. Since the normal upper limit of FeNO for healthy Japanese adults is 37ppb, values of 35ppb or more are likely to be interpreted as a signature of inflammatory condition presenting features with asthma, and this value is used in clinical practice. Research is also underway for clinical application of these measurements in other respiratory diseases such as COPD and interstitial lung disease. Currently, there remains some confusion regarding the significance of these measurements and the interpretation of the results. This statement is designed to provide a simple explanation including the principles of FeNO measurements, the measurement methods, and the interpretation of the measurement results.

Circulating Methemoblogin Fraction in Dogs With Sepsis.

Large amount of nitric oxide (NO) can be released in patients with sepsis. Methemoglobin is formed from the interaction between NO and hemoglobin. Mild methemoglobinemia reflecting NO overproduction has been reported in septic people, and occasionally associated to septic shock and organ dysfunction. The aim of this retrospective study was to evaluate circulating methemoglobin fraction in dogs with sepsis and to assess its prognostic value. Methemoglobin reference interval (RI) was calculated in 41 healthy dogs and was set at 0–2.2%. A total of 131 dogs with sepsis were included in the study; 24/131 had a circulating methemoglobin ≥2.2%. The median methemoglobin fraction was significantly higher in dogs with sepsis compared to healthy ones (1.7%, 0.4–3.5% vs. 1.0, 0.3–2.2%, P = 0.0005). No significant difference was observed between dogs with uncomplicated sepsis (n = 98) vs. dogs with septic shock (n = 33) (1.8%, 0.4–2.8% vs. 1.5%, 0.4–3.5%, P = 0.74), between dogs with and without multi-organ dysfunction (n = 38 and n = 93, respectively) (1.7%, 0.4–3.5% vs. 1.7%, 0.5–2.8%, P = 0.27), and between survivors (n = 77) vs. non survivors (n = 54) (1.5%, 0.4–2.8% vs. 1.8%, 0.4–3.5%, P = 0.05). Dogs with methemoglobin fraction above or equal to the upper limit of the RI had a significantly higher frequency of death compared to dogs with methemoglobin levels <2.2% (60.0% vs. 36.8%, P = 0.04). In conclusion, mild methemoglobinemia is detected in dogs with sepsis, and methemoglobin values above the RI might be associated with a worse outcome.

Low Doses of Arsenic in a Mouse Model of Human Exposure and in Neuronal Culture Lead to S-Nitrosylation of Synaptic Proteins and Apoptosis via Nitric Oxide.

Background: Accumulating public health and epidemiological literature support the hypothesis that arsenic in drinking water or food affects the brain adversely. Methods: Experiments on the consequences of nitric oxide (NO) formation in neuronal cell culture and mouse brain were conducted to probe the mechanistic pathways of nitrosative damage following arsenic exposure. Results: After exposure of mouse embryonic neuronal cells to low doses of sodium arsenite (SA), we found that Ca2+ was released leading to the formation of large amounts of NO and apoptosis. Inhibition of NO synthase prevented neuronal apoptosis. Further, SA led to concerted S-nitrosylation of proteins significantly associated with synaptic vesicle recycling and acetyl-CoA homeostasis. Our findings show that low-dose chronic exposure (0.1–1 ppm) to SA in the drinking water of mice led to S-nitrosylation of proteomic cysteines. Subsequent removal of arsenic from the drinking water reversed the biochemical alterations. Conclusions: This work develops a mechanistic understanding of the role of NO in arsenic-mediated toxicity in the brain, incorporating Ca2+ release and S-nitrosylation as important modifiers of neuronal protein function.

Global NO and HONO emissions of biological soil crusts estimated by a process-based non-vascular vegetation model

Abstract. The reactive trace gases nitric oxide (NO) and nitrous acid (HONO) are crucial for chemical processes in the atmosphere, including the formation of ozone and OH radicals, oxidation of pollutants, and atmospheric self-cleaning. Recently, empirical studies have shown that biological soil crusts are able to emit large amounts of NO and HONO, and they may therefore play an important role in the global budget of these trace gases. However, the upscaling of local estimates to the global scale is subject to large uncertainties, due to unknown spatial distribution of crust types and their dynamic metabolic activity. Here, we perform an alternative estimate of global NO and HONO emissions by biological soil crusts, using a process-based modelling approach to these organisms, combined with global data sets of climate and land cover. We thereby consider that NO and HONO are emitted in strongly different proportions, depending on the type of crust and their dynamic activity, and we provide a first estimate of the global distribution of four different crust types. Based on this, we estimate global total values of 1.04 Tg yr−1 NO–N and 0.69 Tg yr−1 HONO–N released by biological soil crusts. This corresponds to around 20 % of global emissions of these trace gases from natural ecosystems. Due to the low number of observations on NO and HONO emissions suitable to validate the model, our estimates are still relatively uncertain. However, they are consistent with the amount estimated by the empirical approach, which confirms that biological soil crusts are likely to have a strong impact on global atmospheric chemistry via emissions of NO and HONO.

Studies on structural properties and immune-enhancing activities of glycomannans from Schizophyllum commune

Polysaccharides were extracted from Schizophyllum commune (a common mushroom) and their structural and immune-enhancing properties were investigated. Crude and fractions (F1 and F2) were composed of sugars (50.3–82.8%), proteins (1.46–20.1%), and sulfates (1.33–7.01%). Monosaccharide compositions of Cr and F1 were mainly composed of glucose (75.5% and 88.2%) with small amounts of mannose, galactose and xylose whereas the F2 was mainly composed of manose (55.2%) with minor amounts of galactose, glucose, and xylose. Their immune-enhancing activities were tested using RAW264.7 cells. Proliferation activity of RAW264.7 cells was over 100% after treatment with these polysaccharides. In addition, RAW264.7 cells produced large amounts of nitric oxide and various cytokines by up-regulating mRNA expression levels and the activation of nuclear factor-kappa (NF-κB) and mitogen-activated protein kinase (MAPK) after treatment with these polysaccharides. In addition, RAW264.7 cells were activated mainly through CR-3 and TLR-4 receptors. The backbone of F2 with excellent immune-enhancing activity was mainly linked by (1→3)-linked-mannopyranosyl and (1→2,3)-linked-mannopyranosyl residues.

Role of nitric oxide in pathogenesis of tumor growth and its possible application in cancer treatment.

In this review, the role of nitric oxide (NO) in the pathogenesis of the tumor growth and possibilities of its application in the treatment of cancer patients are analyzed. NO is one of the most important mediators of physiological processes being involved in the regulation of practically all body functions in health and disease. The role of NO in the development of many pathological conditions has been extensively studied and debated in recent years. Today it is clear that NO in relation to malignant tumors may exhibit a dual activity- can stimulate tumor growth and cause an opposite antitumor effect. Effects of NO are mostly dependent on its concentration. At low concentrations, NO could inhibit apoptosis and cause mutations that potentially lead to the formation of malignant growth loci. However, a high concentration of NO appears to be detrimental to malignant cells, in particular under conditions of simultaneous exposure to ionizing radiation. In humans, the inducible NO synthase (iNOS, type II) is the most powerful form of NO synthases (NOS) and has the ability to synthesize large amounts of NO for a long time and exert a protective function. iNOS is expressed in macrophages, monocytes, neutrophils, fibroblasts, hepatocytes, and other cell types. In tissue of malignant tumors, the macrophagal iNOS is the main form. Experimental data provide an evidence that activated macrophages and leukocytes, which are the part of peritumorous inflammatory infiltrate, can provide radiosensitization of tumors by direct synthesis of NO and indirectly- through the secretion of cytokines stimulating iNOS activity in cancer cells. Such approach could be useful for the development of new schemes and methods of anticancer therapy based on the activation of endogenous NO biosynthesis pathways.