Nitric Oxide Concentration Research Articles

Seasonal variation in greenhouse gas concentrations and diffusive fluxes in three river–reservoir systems in the Seine Basin (France)

River and reservoir ecosystems have been considered as hot spots for GHG (greenhouse gas) emissions while their specific hydrological and biogeochemical processes affect GHG concentrations; however, few studies integrated river–reservoir systems to identify the dominant drivers of GHG concentrations and flux changes associated with these systems. In the present study, we examined the seasonal variations in GHG concentrations in the surface water of three river-reservoir systems in the Seine Basin. The levels and seasonal variations of GHG concentrations exhibited distinct patterns among reservoirs, upstream, and downstream rivers. The concentrations of CH4 (methane) in the reservoirs were notably higher than those observed in both upstream and downstream rivers and showed higher values in summer and autumn, which contrasted with CO2 (carbon dioxide) concentrations, while N2O (nitrous oxide) concentrations did not show an obvious seasonal pattern. A high mole ratio of CH4/CO2 was found in these reservoirs, with a value of 0.03 and was more than 30 and 10 times higher than that in the upstream and downstream rivers, respectively. The three river–reservoir systems were oversaturated with GHG during the study period, with the average diffusive fluxes (expressed as CO2eq: CO2 equivalent) of 810 ± 1098 mg CO2eq m−2 d−1, 9920 ± 2413 mg CO2eq m−2 d−1, and 7065 ± 2704 mg CO2eq m−2 d−1 in the reservoirs, upstream and downstream rivers, respectively. CO2 and CH4–CO2 were respectively the dominant contributors to GHG diffusive fluxes in river and reservoir sections, while N2O contributed negligibly to GHG diffusive fluxes in the three river–reservoir systems. Our results showed that GHG concentrations and gas transfer coefficient have varying importance in driving GHG diffusive fluxes among different sections of the river–reservoir systems. In addition, our results also show the combined effect of reservoirs and upstream rivers on the water quality variables and hydrological characteristics of downstream rivers, highlighting the future need for additional investigations of GHG processes in the river–reservoir systems.

Association between PM2.5 from a coal mine fire and FeNO concentration 7.5 years later

Background and aimThere are few long-term studies of respiratory health effects of landscape fires, despite increasing frequency and intensity due to climate change. We investigated the association between exposure to coal mine fire PM2.5 and fractional exhaled nitric oxide (FeNO) concentration 7.5 years later.MethodsAdult residents of Morwell, who were exposed to the 2014 Hazelwood mine fire over 6 weeks, and unexposed residents of Sale, participated in the Hazelwood Health Study Respiratory Stream in 2021, including measurements of FeNO concentration, a marker of eosinophilic airway inflammation. Individual exposure to coal mine fire PM2.5 was modelled and mapped to time-location diaries. The effect of exposure to PM2.5 on log-transformed FeNO in exhaled breath was investigated using multivariate linear regression models in the entire sample and stratified by potentially vulnerable subgroups.ResultsA total of 326 adults (mean age: 57 years) had FeNO measured. The median FeNO level (interquartile range [IQR]) was 17.5 [15.0] ppb, and individual daily exposure to coal mine fire PM2.5 was 7.2 [13.8] µg/m3. We did not identify evidence of association between coal mine fire PM2.5 exposure and FeNO in the general adult sample, nor in various potentially vulnerable subgroups. The point estimates were consistently close to zero in the total sample and subgroups.ConclusionDespite previous short-term impacts on FeNO and respiratory health outcomes in the medium term, we found no evidence that PM2.5 from the Hazelwood coal mine fire was associated with any long-term impact on eosinophilic airway inflammation measured by FeNO levels.

The effects of MEPaL on oxidative stress and motor function in the rats affected by prenatal hypoxia

AbstractBackground and objectivesMaternal hypoxia disrupts neural development and subsequently leads to cerebral palsy and epilepsy in newborns. Hypoxia plays a role in neurodegeneration by increasing oxidative stress. Pistacia atlantica is known as an important antioxidant, and its anti‐inflammatory and antioxidant effects have been shown in various studies. This study aims to investigate the effects of methanolic extract of P. atlantica leaves (MEPaLs) on the oxidative parameters in the serum of rats affected by maternal hypoxia.Material and methodsIn this study, eight pregnant rats were used. The newborns were divided into four groups, including the control and the hypoxia groups, which are affected by maternal hypoxia, hypoxia + MEPaL 100 mg/kg, and hypoxia + MEPaL 150 mg/kg. MEPaL was injected (i.p) for 21 days into the neonatal rats after the lactation period. Hypoxia was induced by keeping pregnant rats in a hypoxic chamber with 7% oxygen and 93% nitrogen intensity for 3 h on the 20th day of pregnancy. Behavioral changes were measured using open‐field and rotarod tests. Finally, biomarkers of oxidative stress, nitric oxide (NO), glutathione (GSH), GSSG, TAS, TOS, and oxidative stress index (OSI) were measured in the experimental groups.ResultsBehavioral results showed that the anxiety behavior in the hypoxia group increased, but the motor activity (moved distance and movement speed) decreased. Moreover, the amount of time spent maintaining balance on the rotarod rod was significantly decreased in the hypoxia group. The concentration of NO in the group of hypoxia + MEPaL 100 mg/kg showed a significant decrease, and MEPaL 100, and 150 mg/kg + hypoxia also increased the concentration of GSH and decreased GSSG. In addition, MEPaL100 and 150 mg/kg caused a significant increase in the ratio of GSH to GSSG and decreased OSI and total oxidant capacity.ConclusionsOxidative stress increased in the rats affected by maternal hypoxia and may be the main mechanism for motor activity impairment and balance disturbance, whereas MELaL improved motor performance by decreasing oxidative stress.

A novel, cassette-based nitric oxide delivery system with an advanced feedback control algorithm accurately delivers nitric oxide via the anesthesia machine independent of fresh gas flow rate and volatile anesthetic agent

Nitric oxide (NO), a selective pulmonary vasodilator, can be delivered via conventional ICU and anesthesia machine ventilators. Anesthesia machines are designed for rebreathing of circulating gases, reducing volatile anesthetic agent quantity used. Current cylinder- and ionizing-based NO delivery technologies use breathing circuit flow to determine NO delivery and do not account for recirculated gases; therefore, they cannot accurately dose NO at FGF below patient minute ventilation (MV). A novel, cassette-based NO delivery system (GENOSYL® DS, Vero Biotech Inc.) uses measured NO concentration in the breathing circuit as an input to an advanced feedback control algorithm, providing accurate NO delivery regardless of FGF and recirculation of gases. This study evaluated GENOSYL® DS accuracy with different anesthesia machines, ventilation parameters, FGFs, and volatile anesthetics. GENOSYL® DS was tested with GE Aisys and Dräger Fabius anesthesia machines to determine NO dose accuracy with FGF < patient MV, and with a Getinge Flow-i anesthesia machine to determine NO dose accuracy when delivering various volatile anesthetic agents. Neonatal and adult mechanical ventilation parameters and circuits were used. GENOSYL® DS maintained accurate NO delivery with all three anesthesia machines, at low FGF with recirculation of gases, and with all volatile anesthetic agents at different concentrations. Measured NO2 levels remained acceptable at ≤ 1 ppm with set NO dose ≤ 40 ppm. GENOSYL® DS, with its advanced feedback control algorithm, is the only NO delivery system capable of accurately dosing NO with anesthesia machines with rebreathing ventilation parameters (FGF < MV) regardless of anesthetic agent.

The potential protective effect of Camellia Sinensis in mitigating monosodium glutamate-induced neurotoxicity: biochemical and histological study in male albino rats

Monosodium glutamate (MSG) is the sodium compound derived from glutamic acid. Excessive daily ingestion of MSG leads to elevated amounts of glutamic acid in the bloodstream, which can be detrimental to brain structures. Camellia sinensis, often known as green tea (GT), is a rich source of essential hexogen antioxidants that are necessary for the body. Thirty-two adult male albino rats were divided into four groups (n = 8). Group 1 served as a control -ve group. Group 2 was given GT (1.5 ml/rat/day). Group 3 was given MSG (600 mg/kg/day). Group 4 was given MSG (600 mg/kg/day) and GT (1.5 ml/rat/day). All treatments were given orally for 28 days. MSG administration resulted in significant neurotoxicity in rats that was revealed by the significant reduction of serum concentration of glutathione peroxidase (GPx) and nitric oxide (NO), and the significant elevation of total antioxidant capacity (TAC) accompanied by the significant reduction of levels of serum monoamines (dopamine, serotonin, and norepinephrine) and histological changes in the hippocampus area CA1, dentate gyrus, and cerebellar cortex and positive immunohistochemical staining of glial fibrillary acidic proteins (GFAP) and calretinin. Administration of GT with MSG counteracted the MSG-mediated oxidative stress by significantly increasing serum concentrations of GPX and NO and significantly decreasing concentrations of TAC. Furthermore, GT significantly increased levels of serum monoamines (dopamine, serotonin, and norepinephrine). Moreover, it ameliorated the histological changes, GFAP, and calretinin immunostaining in brain tissues. It is envisaged that GT will serve as a viable protective choice for the inclusion of the neurotoxicity treatment procedure.

A phase 1, multi-center, safety, feasibility, and preliminary efficacy study evaluating a single dose of UNO101 in relapsed or refractory, unresectable, primary, or metastatic cutaneous and subcutaneous malignancies.

TPS2686 Background: Tumor ablation is a minimally invasive technique commonly used to treat solid tumors in the liver, kidney, bone, and lung and is usually based on thermal and nonthermal approaches. Local and in-situ tumor ablation methods demonstrate enhanced anti-tumor immune responses resulting in the destruction of residual malignant cells in primary tumors and distant metastases. Nitric oxide (NO) is a colorless gas and a short-lived free radical. It is a ubiquitous, endogenously generated gas implicated in the homeostatic regulation of physiological processes. Preclinical studies evaluating the effect of high concentration exogenously administered NO demonstrated its anti-cancer properties and suggested that it may serve as a potent tumoricidal agent. We have previously shown that treating mouse colon carcinoma (CT26) tumor-bearing mice with ultra-high concentrations of nitric oxide (UNO101) upregulates innate and adaptive immune cells both locally and systemically. Beyond Cancer is currently conducting a first-in-human, first-in-class, Phase 1 safety, feasibility, and preliminary efficacy clinical study of UNO101 at multiple institutions in Israel. Methods: The study is a 2-part Phase 1 trial with a Dose Escalation and a Dose Expansion portion (NCT05351502). A conventional 3+3 dose escalation will evaluate three cohorts of UNO101 single dose: 25,000, 50,000 and 100,000 parts per million (PPM) delivered intratumorally over 5 minutes in subjects with an ECOG PS of 0–3, at least 3 months of life expectancy, with relapsed or refractory unresectable primary or metastatic cutaneous and subcutaneous measurable solid tumors being eligible for enrollment. Upon determination of the maximum tolerated dose or biological effective dose, whichever occurs first, the proposed recommended Phase 2 dose will be further evaluated in the Dose Expansion portion of the study. RECIST version 1.1 and iRECIST will be utilized to assess the rate of malignant tumor response after UNO administration and toxicity will be graded per NCI CTCAE version 5.0. Evaluation of response per itRECIST will also be explored. Up to thirty-eight enrolled subjects are anticipated. Cohort 1, 25,000 PPM have been completed without a reported DLT. Enrollment to Cohort 2, 50,000 PPM, began in January 2024. This study was approved by Israel Ministry of Health (IMOH) as well as the participating institution’s Ethics Board. Written informed consent was obtained for all enrolled subjects and a copy of the written consent is available for review. Clinical trial information: NCT05351502 .

Effect of UNO101 on tumor microenvironment in relapsed or refractory, unresectable, primary, or metastatic cutaneous and subcutaneous malignancies.

e14575 Background: Nitric oxide (NO) is a ubiquitous, endogenously generated gas implicated in the homeostatic regulation of physiological processes, and NO is implicated in numerous pathological conditions. Preclinical studies evaluating the effect of high concentration exogenously administered NO demonstrated anti-cancer properties and suggested that it may serve as a potent tumoricidal agent. We have previously shown that treating mouse colon carcinoma (CT26) tumor-bearing mice with ultra-high concentrations of nitric oxide (UNO) upregulates innate and adaptive immune cells locally and systemically. Methods: Upon a signed written ICF, a single UNO101 dose of 25,000 parts per million (ppm), administered intratumorally over 5 minutes, was evaluated in relapsed or refractory, unresectable, primary, or metastatic cutaneous and subcutaneous malignancies. Subjects with an ECOG PS of 0–3, at least 3 months of life expectancy and tumor size of 4.5 mm minimum and 30 mm maximum length were eligible for enrollment. RECIST v1.1 and clinical physical examination by PI assessment was utilized to assess the rate of malignant tumor response. Toxicity was graded per NCI CTCAE v5.0. Results: In this first-in-human Phase 1 clinical trial, six subjects, 4F/2M were enrolled with a median age of 61.5 years, (range, 34–81) and ECOG PS reported as 0 or 1. Tumor types enrolled included breast (n=3), melanoma (n=1), and squamous cell carcinoma (n=2) with a median of 4 prior lines of therapy (range, 2–11) and a median of 4.7 years (range, 1.4–9.5) since time of diagnosis to study entry. One related SAE (not dose limiting) of hypoxia, Grade 4, was reported, which resulted in cessation of UNO101 treatment after 1:55 minutes. The other five administrations were completed successfully, with no further SAEs. Other reported drug related AEs were primarily Grade 1 that resolved/recovered without sequelae. Clinical immune blood biomarkers post UNO101 treatment demonstrated modulation of the tumor microenvironment by upregulating of cytotoxic T-cells (11.1%), T-central memory cells (190.6%) as a percent of total T-cells, and dendritic cells (231.4%) as a percentage of WBCs, from baseline to Day 21. Further, T-regulatory cells (38.0%) were downregulated as a percentage of total T-cells from baseline to Day 21. Based on available physical examination and caliper measurements, clinical presentation on Day 7 on two subjects, significant clinical responses were observed. Conclusions: To date,a single dose of UNO101 at 25,000 ppm is well tolerated, with biomarkers suggesting immune action within the tumor microenvironment, trending in a favorable direction on Day 21 in a heavily pre-treated population. Additional UNO101 single dose of 50,000 ppm, and possibly 100,000 ppm, will be further evaluated for safety/tolerability, impact on immune biomarkers, and preliminary efficacy. Clinical trial information: NCT05351502 .

Aphrodisiac Potential of Tiger Nut (Cyperus esculentus L.) Powder in Male Wistar Albino Rat

This study aimed to assess the aphrodisiac potential of tiger nuts (Cyperus esculentus L.) powder in male Wistar albino rats. Twenty-five male and twenty-five female rats were used for the experiment. The male rats were selected into five groups of 5 rats/group. Two groups served as normal and positive controls. Three groups were fed with feed supplemented with varying concentrations of Cyperus esculentus powder (5%, 10%, and 20%) for fourteen (14) days. After the treatment, sexual behaviors, fasting blood glucose, lipid profile, nitric oxide, and some sex hormone levels were assayed. The results showed a significant variation in mount frequencies, while significant increases were observed in intromission frequency and intromission ratio as compared to the normal control. Significant increases in the body weight of both the normal control and treated groups were observed. However, the fasting blood glucose level was not altered significantly. Lipid profile levels were increased in rats fed a 20% tiger nut supplementary diet when compared with the control, whereas low-density lipoprotein was not changed significantly. Nitric oxide concentration significantly increased in the testes but decreased in the kidneys of the treated groups. The results of sex hormone levels showed a significant increase in follicle-stimulating hormone and testosterone with no variation in luteinizing hormone. These results showed that Cyperus esculentus powder can improve the sexual behavior of male rats, hence giving credence to the aphrodisiac potential of Cyperus esculentus.

Non-uniform line-of-sight measurements of nitric oxide using mid-infrared Faraday rotation spectroscopy

Traditional absorption spectroscopy relies on detecting intensity variations along the line-of-sight to gauge average concentration and temperature. While methods like profile fitting and temperature binning offer insights into the non-uniformity of the path, they fall short of accurately capturing the precise spatial distribution with a single line-of-sight measurement. We propose a novel measurement scheme for non-uniformly distributed concentration of nitric oxide (NO) along the line-of-sight utilizing a single laser and path, by incorporating Faraday rotation spectroscopy with magnetic fields changing over time and space. We validate the proposed scheme by measuring a path of two regions in series with different NO concentrations, and comparing the measurement results with direct absorption spectroscopy of each respective region. In this work, the tuning range of the interband cascade laser used is from 1899.42 to 1900.97 cm−1, encompassing two sets of spectral lines corresponding to the 2Π1/2 and 2Π3/2 transitions of NO’s R(6.5). The average relative uncertainty in the concentration measurement for each region is estimated to be within 1.5%, with the concentration for individual absorption cells ranging from 0.2% to 0.8%.

The Impact of Environmental Gaseous Pollutants on the Cultivable Bacterial and Fungal Communities of the Aerobiome.

Understanding air microbial content, especially in highly polluted urban areas, is crucial for assessing its effect on human health and ecosystems. In this context, the impact of gaseous pollutants on the aerobiome remains inconclusive due to a lack of studies separating this factor from other contaminants or environmental factors. In this study, we aimed to experimentally assess the influence of contrasting concentrations of atmospheric gaseous pollutants as isolated variables on the composition of the aerobiome. Our study sites were contrasting Air Quality Index (AQI) sites of the Metropolitan Region of Chile, where nitric oxide (NO) was significantly lower at the low-AQI site than at the high-AQI site, while ozone (O3) was significantly higher. Cultivable aerobiome communities from the low-AQI site were exposed to their own pollutants or those from the high-AQI site and characterized using high-throughput sequencing (HTS), which allowed comparisons between the entire cultivable communities. The results showed increased alpha diversity in bacterial and fungal communities exposed to the high-AQI site compared to the low-AQI site. Beta diversity and compositional hierarchical clustering analyses revealed a clear separation based on NO and O3 concentrations. At the phylum level, four bacterial and three fungal phyla were identified, revealing an over-representation of Actinobacteriota and Basidiomycota in the samples transferred to the high-AQI site, while Proteobacteria were more abundant in the community maintained at the low-AQI site. At the functional level, bacterial imputed functions were over-represented only in samples maintained at the low-AQI site, while fungal functions were affected in both conditions. Overall, our results highlight the impact of NO and/or O3 on both taxonomic and functional compositions of the cultivable aerobiome. This study provides, for the first time, insights into the influence of contrasting pollutant gases on entire bacterial and fungal cultivable communities through a controlled environmental intervention.

Identification of Xuanfei Baidu granule constituents by liquid chromatography-quadruple-time-of-flight-mass spectrometry and its anti-inflammatory active constituents using a lipopolysaccharide-induced RAW264.7 cell model.

The Xuanfei Baidu (XFBD) prescription, a traditional Chinese medicine prescription, has demonstrated significant anti-inflammatory activities; however, the number of its reported constituents is limited, and its anti-inflammatory constituents are unclear. In this study, the constituents of XFBD granule, a granule dosage of XFBD prescription, were thoroughly examined in vitro and in vivo using liquid chromatography-quadruple-time-of-flight-mass spectrometry, and the anti-inflammatory constituents were screened. A total of 214 constituents were identified from the XFBD granule, 62 of which were confirmed via comparison with reference standards. After intragastric administration of XFBD granule, 63 and 28 constituents were absorbed into the rat sera and lungs in prototype form, respectively. XFBD granule and XFBD-containing serum were found to significantly reduce nitric oxide (NO) and interleukin-6 (IL-6) secretion in lipopolysaccharide-induced RAW264.7 cells. Five anti-inflammatory constituents (verbasoside, scutellarin, luteolin, apigenin, and pogostone) were found to reduce the concentration of NO and IL-6 in a dose-dependent manner. Moreover, the combination of these five constituents could significantly reduce NO secretion even when the concentration of each constituent was two to three orders of magnitude lower than their individual minimum effective concentrations. Overall, this study provides a valuable reference for the discovery of effective constituents from the XFBD granule.

The effects of saline water consumption on sperm parameters, testicular histopathology, hormonal and antioxidants concentrations in Barki Rams

The study aimed to assess the effects of water salinity on the sperm parameters, levels of cortisol, LH, FSH, testosterone and antioxidants as well as the testes’ histopathology in Barki rams. Fifteen healthy Barki rams (1–1.5 years) were divided into three equal depending on the type of drinking water for nine months. The rams in the tap water group (TW, water that contained 350 ppm of total dissolved salts (TDS). Males in the high saline water group (HSW) were permitted to consume high saline water with 8,934 ppm TDS, whereas those in the second group were permitted to have moderately saline water (MSW, 4,557 ppm TDS). High salt concentration in drinking water had adverse effect on sperm viability, morphology and sperm cell concertation. Nitric oxide and malondialdehyde concentrations in blood were significantly higher in the MSW and HSW groups than in TW. There was a significant decrease in glutathione concentration as well as superoxide dismutase activity in TDS and HSW. Cortisol was most highly concentrated in the HSW, next in the MSW, and least in TW. The testosterone, LH, and FSH concentrations in the HSW and MSW groups were significantly lower than in TW. As the salt concentration in drinking water increases, damage to testicular tissue. The MSW group demonstrating vacuolation of lining epithelial cells with pyknotic nuclei in the epididymis and necrosis and desquamation of spermatogenic cells in seminiferous tubules while HSW group displaying desquamated necrotic cells and giant cell formation in the epididymis, as well as damage to some of the seminiferous tubules and showed congestion, vacuolation of spermatogenic epithelium of seminiferous tubules, and desquamated necrotic spermatogenic epithelium. In conclusion, the salinity of the water has detrimental impacts on the sperm morphology, viability and concentration, hormones and antioxidant levels in Barki rams.

#2799 Myoglobin removal by hemadsorption: ex-vivo adsorption kinetics

Abstract Background and Aims Myoglobin, due to its molecular weight of 17 kDa and a Einstein-Stoke radius greater than expected, is classed as a middle molecular weight uremic toxin and presents a two-compartment model of distribution in the body. Rhabdomyolysis is a condition in which muscle cell content including myoglobin, are released into blood circulation due to severe injury to the muscle. Circulating myoglobin induces renal injury with several mechanisms: reduced concentration of nitric oxide in medullary renal arterioles, production of free radicals with oxidative stress, tubular necrosis as a consequence of tubular obstruction by myoglobin and cellular debris. A possible therapeutic option is the use of High Cut-off membranes but with the risk of significant loss of albumin and other proteins. The use of adsorption can overcome these limitations. The aim of our study is to assess the adsorption of myoglobin with neutral microporous styrene-divinylbenzene copolymer sorbent (e.g., HA330/380, Jafron Biomedical CO, Lts, Zhuhai City, China). Method Using a downscaled module of HA380 Cartridge, we set up an ex-vivo circulation experiment in which 1 liter of plasma containing 0.1 mg of myoglobin was pumped through the cartridge. We collected samples (3 mL) at different timepoints to measure Myoglobin concentration. We calculated the removal ratio (RR) and mass adsorbed at a given timepoints. Results Initial myoglobin concentration was 99.3 ng/ml. Final myoglobin concentration after 4 hours of experiment was 30.6 ng/ml. Removal Ratio at 4 hour was 69 % and mass adsorption of 0.068 mg of myoglobin. Conclusion To our knowledge, this is the first experiment that assessed the adsorption capacity of polystyrene-divinylbenzene sorbent. Our study, demonstrated high adsorption capacity in the first 4 hours of treatment therefore, confirming the possibility to use adsorption as an effective treatment option in rhabdomyolysis and avoiding complications associated to current dialytic treatment.

Using Metalloporphyrin Nanosensors for In Situ Monitoring and Measurement of Nitric Oxide and Peroxynitrite in a Single Human Neural Progenitor Cell.

Nitric oxide (NO) is an inorganic signaling molecule that plays a crucial role in the regulation of numerous physiological functions. An oxidation product of the cytoprotective NO is cytotoxic peroxynitrite (ONOO-). In biological systems, the concentrations of NO and ONOO- are typically transient, ranging from nanomolar to micromolar, and these increases are normally followed by a swift return to their basal levels due to their short life spans. To understand the vital physiological role of NO and ONOO- in vitro and in vivo, sensitive and selective methods are necessary for direct and continuous NO and ONOO- measurements in real time. Because electrochemical methods can be adjusted for selectivity, sensitivity, and biocompatibility in demanding biological environments, they are suitable for real-time monitoring of NO and ONOO- release. Metalloporphyrin nanosensors, described here, have been designed to measure the concentration of NO and ONOO- produced by a single human neural progenitor cell (hNPC) in real time. These nanosensors (200-300 nm in diameter) can be positioned accurately in the proximity of 4-5 ± 1 μm from an hNPC membrane. The response time of the sensors is better than a millisecond, while detection limits for NO and ONOO- are 1 × 10-9 and 3 × 10-9 mol/L, respectively, with a linear concentration response of up to about 1 μM. The application of these metalloporphyrin nanosensors for the efficient measurement of the concentrations of NO and ONOO- in hNPCs is demonstrated, providing an opportunity to observe in real time the molecular changes of the two signaling molecules in situ.

Enhancing Control Over Nitric Oxide Photorelease via a Molecular Keypad Lock.

Based on Boolean logic, molecular keypad locks secure molecular information, typically with an optical output. Here we investigate a rare example of a molecular keypad lock with a chemical output. To this end, the light-activated release of biologically important nitric oxide from a ruthenium complex is studied, using proton concentration and photon flux as inputs. In a pH-dependent equilibrium, a nitritoruthenium(II) complex is turned into a nitrosylruthenium(II) complex, which releases nitric oxide under irradiation with visible light. The precise prediction of the output nitric oxide concentration as function of the pH and photon flux is achieved with an artificial intelligence approach, namely the adaptive neuro-fuzzy inference system. In this manner an exceptionally high level of control over the output concentration is obtained. Moreover, the provided concept to lock a chemical output as well as the output prediction may be applied to other (photo)release schemes.

Effect of Hydrotherapy and Physical Activity on Uric Acid and Nitric Oxide Concentrations in Serum Samples

Hydrotherapy is highly recommended for older adults because it offers warmth and support, so people with pain or reduced mobility and balance can move and exercise more freely compared to regular physical activity. The high plasma antioxidant capacity of uric acid in neutralizing oxidative species and the importance of nitric oxide (NO) in vasodilation and inflammatory response are relevant in older adults. This work aimed to evaluate hydrotherapy's effect on uric acid and NO concentrations in a population aged ≥ 60 years before and after hydrotherapy. A randomized study with 37 individuals was divided into two groups: the experimental group, which was evaluated at two time points: T0-before treatment and T1-after 15-hydrotherapy sessions, and the control group, which did not practice any exercise. The determinations of uric acid and NO levels in serum were carried out by spectrophotometry. Statistics were carried out with SPSS. The experimental group showed a significant increase in the concentration of uric acid in T1 compared to T0. NO results did not show significant differences between T0 and T1. Regular hydrotherapy increases the concentration of serum uric acid, potentially beneficial in the performance of antioxidant functions, reducing oxidative stress, delaying aging, and improving the well-being of older adults.

Cannabidiol prevents LPS-induced inflammation by inhibiting the NLRP3 inflammasome and iNOS activity in BV2 microglia cells via CB2 receptors and PPARγ

Neuroinflammation stands as a critical player in the pathogenesis of diverse neurological disorders, with microglial cells playing a central role in orchestrating the inflammatory landscape within the central nervous system. Cannabidiol (CBD) has gained attention for its potential to elicit anti-inflammatory responses in microglia, offering promising perspectives for conditions associated with neuroinflammation. Here we investigated whether the NLRP3 inflammasome and inducible nitric oxide synthase (iNOS) are involved in the protective effects of CBD, and if their modulation is dependent on cannabinoid receptor 2 (CB2) and PPARγ signalling pathways. We found that treatment with CBD attenuated pro-inflammatory markers in lipopolysaccharide (LPS)-challenged BV2 microglia in a CB2- and PPARγ-dependent manner. At a molecular level, CBD inhibited the LPS-induced pro-inflammatory responses by suppressing iNOS and NLRP3/Caspase-1-dependent signalling cascades, resulting in reduced nitric oxide (NO), interleukin-1β (IL-1β), and tumour necrosis factor-alpha (TNF-α) concentrations. Notably, the protective effects of CBD on NLRP3 expression, Caspase-1 activity, and IL-1β concentration were partially hindered by the antagonism of both CB2 receptors and PPARγ, while iNOS expression and NO secretion were dependent exclusively on PPARγ activation, with no CB2 involvement. Interestingly, CBD exhibited a protective effect against TNF-α increase, regardless of CB2 or PPARγ activation. Altogether, these findings indicate that CB2 receptors and PPARγ mediate the anti-inflammatory effects of CBD on the NLRP3 inflammasome complex, iNOS activity and, ultimately, on microglial phenotype. Our results highlight the specific components responsible for the potential therapeutic applications of CBD on neuroinflammatory conditions.

Melatonin administration during the first half of pregnancy improves physiological response and reproductive performance of rabbits under heat stress conditions.

Context Melatonin may have a heat-stress-alleviating role during pregnancy. Aims To investigate the effects of melatonin administration during the first half of pregnancy on heat-tolerance capacity and pregnancy outputs of naturally heat-stressed rabbits. Methods Forty female rabbits were stratified equally into two experimental groups and daily received 1mg melatonin/kg body weight or not (control) for 15 consecutive days post-insemination. Heat tolerance indices, hormone profile, ovarian structures, and fetal loss were determined. Key results Treatment with melatonin significantly decreased respiration rate and rectal temperature, improved concentrations of nitric oxide, and tended to decrease malondialdehyde concentrations (P =0.064) compared to control. Melatonin treatment significantly increased concentrations of high-density lipoprotein, oestradiol, and progesterone compared to control. No significant differences in the numbers of visible ovarian follicles, corpora lutea, and total implantation sites on day 18 of pregnancy were observed between experimental groups. However, melatonin treatment significantly reduced the number of absorbed implantation sites and significantly improved amniotic fluid volume and conception rate compared to control. Conclusions Melatonin administration during the first half of pregnancy can improve reproductive performance of heat-stressed female rabbits. Implications Melatonin can improve fetal survivability via improving heat-tolerance capacity of does and steroidogenesis.

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.

Correction of Nitrosative Stress During Reparative Regeneration of the Nasal Cavity Mucosa in an Experimental

Introduction. Nitric oxide metabolites play an important role in prolongation of the inflammatory reaction, disorders of epithelial regeneration in diseases of the upper respiratory tract. One of the promising approaches to regulating the bioactivity of nitric oxide is the use of antioxidants.The objective of the study is to evaluate the effectiveness of antioxidant therapy for the correction of nitrosative stress during reparative regeneration of the nasal mucosa in an experiment.Methods. A preclinical randomized experimental study is conducted on 160 rats, divided into 4 groups. The control group (n = 40) consists of intact animals. Animals in experimental group 1 (n = 40) do not receive treatment aſter injury; in group 2 (n = 40) anti-inflammatory treatment is prescribed. The third group consists of laboratory rats (n = 40), which are additionally injected into the nasal cavity with an antioxidant — a 15 % solution of 1,1-dimethyl-3-oxobutylphosphonic acid dimethyl ester. On days 2, 5, 10, and 14 of observation, the concentration of nitrates and nitrites and C-reactive protein in the blood of animals are determined.Results. In group 3, aſter an increase in the level of nitric oxide metabolites on day 2 aſter injury on day 5, a significant (p &lt; 0.05) decrease was noted in comparison with other groups, and by day 10— normalization of the indicator. An increase in the level of C-reactive protein in blood serum correlated with the concentration of nitric oxide metabolites.Discussion. The optimal therapeutic effect when taking antioxidants develops when administered in the first hours aſter injury to reduce the excessive formation of reactive nitrogen radicals. However, the duration of administration should not exceed 4–5 days to avoid a significant decrease in the level of nitric oxide metabolites and deterioration of mucosal regeneration.Conclusions. Assessment of nitric oxide metabolitesin the blood at different times aſter injury is an important marker of inflammatory activity. The use of antioxidants helps to reduce the concentration of active nitrogen radicals.