NO Levels Research Articles

Enhanced Anticancer Efficacy of Alkaline Plasma-Activated Water through Augmented RONS Production.

Despite notable advances in anticancer drug development, their manufacture and use pose environmental and health risks due to toxic byproducts, drug residue contamination, and cytotoxicity to normal cells. Therefore, developing cost-effective anticancer treatments with fewer toxic side effects and higher selectivity is essential to the advancement of highly effective anticancer therapies. Plasma-activated water (PAW) offers a green alternative to conventional chemical treatments as it reverts to water within days. However, the limited duration and dose of reactive oxygen and nitrogen species (RONS) in acidified PAW restrict its clinical deployment and the full understanding of their mechanism. In this study, we propose alkaline PAW as an innovative enhancement of the RONS technology. The alkaline PAW generated markedly superior RONS, with about 10 times higher levels of NO2-, H2O2, and ONOO-/O2•- than acidic PAW. The possible RONS generation pathways in alkaline PAW are analyzed by scavengers. In conventional acidic PAW, 70% of the H2O2 concentration is contributed by •OH but only about 20% in alkaline PAW. ONOO- is mainly formed through the reaction of O2•- with NO in alkaline pH, while in acidic PAW, it mainly forms from NO2- and H2O2. The results unveiled the synergistic and formidable anticancer effects of alkaline PAW against cancer cells, typified by an increase in intracellular ROS/RNS levels. Furthermore, alkaline PAW injection also effectively prevented xenograft tumor growth in mice. We systematically investigated this high-dose anticancer solution without using noble gases, toxic reagents, or extra energy consumption and successfully demonstrated the possibility of alkaline PAW being an effective and environmentally friendly therapeutic technology. The activity is closely linked to the RONS dose, and the generation pathway provides much-needed insight into the fundamental aspects of PAW chemistry required for the optimization of the biochemical activity of PAW.

Arginine–NO pathway modulated energy metabolism in the hepatopancreas and muscle of female Litopenaeus vannamei

Currently, the regulational effect of arginine on the energy metabolism is unknown in broodstock shrimp nutrition. Accordingly, an eight-week feeding trial was conducted to confirm it in female Litopenaeus vannamei. Six diets were formulated to contain graded levels of arginine (2.90 %, 3.58 %, 4.08 %, 4.53 %, 5.04 % and 5.55 %). A total of 540 shrimp (with an initial weight of approximately 14 g) were allocated at random to six treatments, each of which consisted of three tanks with 30 shrimp each. The results showed that with the rise in the level of dietary arginine supplementation, growth performance showed an increasing trend, reaching the highest value in the 5.55 % arginine group. The gene expression of cellular energy sensor AMP-activated protein kinase was up-regulated in muscle and hepatopancreas. Dietary arginine supplementation decreased hemolymph glucose content and hepatopancreas crude lipid content, increased muscle crude lipid content, glycogen content in muscle and hepatopancreas. Dietary arginine increased muscle crude protein content, decreased hepatopancreas crude protein content and activated the target of rapamycin 1 pathway. Above results were further confirmed by gene expression. In addition, shrimp were injected with dsGFP and dsNOS for 48 h and successfully constructed the RNA interference model. The findings showed that the levels of nos, cgmp, ampk (a, b, c), genes involved in glucose metabolism, lipid metabolism and amino acid metabolism were inhibited. In the conclusion, arginine supplementation could promote growth performance through modulating energy metabolism. Arginine–NO pathway modulated energy metabolism in hepatopancreas and muscle to promote tissue glycogen synthesis, muscle protein and lipid deposition in female L. vannamei.

Role of Vitamin D and E as Antioxidants Against Cerebral Endothelial Dysfunction: An In Vivo Study in White Rats (Rattus norvegicus) Sepsis Model

Sepsis is a life-threatening condition caused by the body's response to an infection, leading to organ dysfunction. A antioxidants can help neutralize harmful free radicals that cause cellular and tissue damage through oxidative stress. Vitamin D and E are two antioxidants that have been extensively studied for their potential effectiveness. This study aims to evaluate the effectiveness of vitamins D and E in reducing oxidative stress in the cerebral vascular endothelial cells of Wistar mice in a sepsis model. The study follows an experimental design and uses a posttest with a control group. The levels of NO and SOD in 24 sepsis model mice were measured using ELISA, and the cerebral endothelial tissues were examined histopathologically. An ANOVA test was performed, followed by the Post Hoc LSD test. NO and SOD levels decreased in sepsis rats from 66.88 ± 16.59 to 88.77 ± 12.83µmol/L. Sepsis mice given vitamin D and E showed significant results on changes in NO and SOD levels (p<0.05). Based on the histopathological results of necrosis, inflammation, and hemorrhagic cell damage in sepsis rats reached over 50% of the field of view, significantly different from sepsis mice that had been given vitamin D and E. Sepsis mice were given vitamin D and E influenced 96.2% and 98.7% on changes in NO, SOD, and cerebral endothelial dysfunction (p<0.05). These findings imply that vitamins D and E may be beneficial in managing sepsis-induced cerebral endothelial dysfunction, potentially impacting the treatment and outcomes of sepsis patients.

Immunostimulatory activity of sea buckthorn polysaccharides via TLR2/4-mediated MAPK and NF-κB signaling pathways in vitro and in vivo

SP0.1–1, derived from Sea buckthorn (Hippophae rhamnoides L.), has been discovered to exhibit unique antioxidant activity. In this study, we investigated the immunomodulatory activity and mechanisms of SP0.1–1 on macrophage RAW 264.7 cells in vitro and immunosuppressive mice induced by cyclophosphamide in vivo. The results indicated SP0.1–1 strengthened the immune functions via promoting the proliferation of RAW264.7 cells and phagocytic activity, along with stimulating the release of NO, ROS and cytokines including TNF-α, IL-6, IL-1β and IFN-γ. Western blot and molecular docking analysis demonstrated that SP0.1–1 attached to the prime receptors TLR2 and TLR4 in RAW264.7 cells, and triggered the activation of MyD88-mediated MAPK and NF-κB signaling pathways, thereby exerting the immune response in RAW264.7 cells. However, the intervention of specific inhibitors against TLR2, TLR4, JNK, ERK, p38 and NF-κB blocked the TLR-mediated MAPK and NF-κB signaling pathways and downregulated the levels of NO and the aforementioned cytokines, thus suppressing the activation of macrophages. Therefore, it can be speculated that SP0.1–1 activated the macrophages principally via the TLR2/4-MyD88-mediated MAPK and NF-κB signaling pathways. Additionally, SP0.1–1 could protect against the cyclophosphamide-induced immunosuppression in mice, manifested by the improvement of body weight, immune organ indices, phagocytic index, and the relievement of spleen damage, along with the enhancement of cytokines TNF-α, IL-6, IFN-γ and immunoglobulin IgG and IgM. These findings will shed light on the molecular mechanism of SP0.1–1 on the immunoregulatory effect, and lay the foundation for exploiting a potential immunostimulatory agent of SP0.1–1.

NO2 mapping of Perth bushfire utilizing Sentinel-5P TROPOMI

Abstract In the face of escalating environmental concerns, effective management of air quality remains critical. This study focuses on Perth, Australia, a region impacted by frequent bushfires and industrial emissions, necessitating precise monitoring of atmospheric pollutants like NO2. Leveraging advanced remote sensing technologies, including Sentinel-2 and Sentinel-5P satellites, this research assesses the spatial and temporal dynamics of NO2 before, during, and after the 2021 Wooroloo bushfire. A key objective was to convert satellite-derived NO2 data from mol/m2 to μg/m3 to enable accurate environmental assessment. This conversion utilized a unit conversion method, improving accuracy metrics substantially, with a correlation coefficient (r) increasing from 0.59 to 0.82 and root mean square error (RMSE) decreasing from 7.58 μg/m3 to 3.20 μg/m3. A regression model, validated with ground-level measurements, demonstrates robust predictive capability (R2 = 0.76, RMSE = 2.58 μg/m3), aiding in the creation of NO2 distribution maps across Greater Perth. Comparison with six ground stations revealed varying accuracy (RMSE: 2.9249 to 7.2705 μg/m3), likely influenced by proximity to the fire and prevailing wind directions. Spatiotemporal analysis depicted distinct NO2 patterns: stable levels pre-fire, dramatic increases during, and gradual post-fire recovery. Maximum NO2 concentrations peaked during the fire (up to 79.227 μg/m3), exceeding air quality guidelines. Post-fire, concentrations normalized, yet sporadic peaks persisted, indicating an ongoing environmental impact. Furthermore, analysis of environmental parameters such as Land Surface Temperature (LST), precipitation, and Normalized Difference Vegetation Index (NDVI) during the study period revealed significant correlations with NO2 levels. LST showed a positive correlation (r = 0.64) with NO2 concentrations during the fire, suggesting temperature influences on atmospheric stability and pollutant dispersion. Precipitation exhibited a negative correlation (r = −0.52), indicating its role in scavenging NO2 from the atmosphere post-fire. NDVI displayed a weak negative correlation (r = −0.30), reflecting vegetation recovery trends post-fire. This comprehensive study integrates advanced remote sensing with statistical modelling to enhance air quality monitoring and inform decision-making in bushfire-prone regions. By elucidating NO2 dynamics and their environmental implications, this research contributes essential insights for mitigating air pollution and safeguarding public health amidst climate-induced challenges.

MAM7 from Vibrio parahaemolyticus: Expression, purification and effects on RAW264.7cells.

V. parahaemolyticus is a Gram-negative bacterium that causes gastroenteritis. Within the realm of bacterial interactions with the gut, the outer membrane protein MAM7 plays a key role. However, the precise function of MAM7 in intestinal inflammation, particularly its interactions with macrophages, remains unclear. In this study, we successfully expressed and purified recombinant MAM7. After optimization of the MAM7 expression condition, it was found that the optimal concentration and temperature were 0.75mM and 15°C, respectively, resulting in a 27-fold increase in its yield. Furthermore, RAW264.7 cytotoxicity assay was conducted. The CCK-8 results revealed that MAM7 substantially stimulated the proliferation of RAW264.7cells, with its optimal concentration determined to be 7.5μg/mL. Following this, the NO concentration of MAM7 was tested, revealing a significant increase (p<0.05) in NO levels. Additionally, the relative mRNA levels of IL-1β, IL-6, and TNF-α in RAW264.7cells were measured by qRT-PCR, showing a remarkable elevation (p<0.05). Moreover, ELISA results demonstrated that MAM7 effectively stimulated the secretion of IL-6 and TNF-α by RAW264.7cells. In summary, these findings strongly suggest that MAM7 serves as a proinflammatory adhesion factor with the capacity to modulate immune responses.

Reprint of: M1 Macrophage-Targeted Curcumin Nanocrystals with l-Arginine-Modified for Acute Lung Injury by Inhalation.

Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) with clinical manifestations of respiratory distress and hypoxemia remains a significant cause of respiratory failure, boasting a persistently high incidence and mortality rate. Given the central role of M1 macrophages in the pathogenesis of acute lung injury (ALI), this study utilized the anti-inflammatory agent curcumin as a model drug. l-arginine (L-Arg) was employed as a targeting ligand, and chitosan was initially modified with l-arginine. Subsequently, it was utilized as a surface modifier to prepare inhalable nano-crystals loaded with curcumin (Arg-CS-Cur), aiming for specific targeting of pulmonary M1 macrophages. Compared with unmodified chitosan-curcumin nanocrystals (CS-Cur), Arg-CS-Cur exhibited higher uptake in vitro by M1 macrophages, as evidenced by flow cytometry showing the highest fluorescence intensity in the Arg-CS-Cur group (P < 0.01). In vivo accumulation was greater in inflamed lung tissues, as indicated by small animal imaging demonstrating higher lung fluorescence intensity in the DiR-Arg-CS-Cur group compared to the DiR-CS-Cur group in the rat ALI model (P < 0.05), peaking at 12 h. Moreover, Arg-CS-Cur demonstrated enhanced therapeutic effects in both LPS-induced RAW264.7 cells and ALI rat models. Specifically, treatment with Arg-CS-Cur significantly suppressed NO release and levels of TNF-α and IL-6 in RAW264.7 cells (p < 0.01), while in ALI rat models, expression levels of TNF-α and IL-6 in lung tissues were significantly lower than those in the model group (P < 0.01). Furthermore, lung tissue damage was significantly reduced, with histological scores significantly lower than those in the CS-Cur group (P < 0.01). In conclusion, these findings underscore the targeting potential of l-arginine-modified nanocrystals, which effectively enhance curcumin concentration in inflammatory environments by selectively targeting M1 macrophages. This study thus introduces novel perspectives and theoretical support for the development of targeted therapeutic interventions for acute inflammatory lung diseases, including ALI/ARDS.

Cornus mas (Cornelian Cherry) Exerts Neuroprotective Effects on Cerebral Ischemia/Reperfusion Injury via Anti-Inflammatory and Antioxidant Properties

Background: Stroke is one of the most important causes of mortality and disability in the world. Over 80% of strokes are ischemic, resulting from blockages in cerebral arteries. Increasing evidence suggests that enriching the diet with nutritional antioxidants could decrease brain damage and enhance cognitive function. Cornelian cherry has anti-inflammatory and antioxidant properties and is introduced as a potential source of active ingredients, like anthocyanins, vitamin C, phenolic compounds, and minerals. Objective: Our research study aimed to evaluate the neuroprotective impact of Cornus mas L. (cornelian cherry) on a rat model of Cerebral Ischemia/Reperfusion Injury (CIRI). Methods: Middle cerebral artery blockage induced CIRI for 60 minutes. After inducing CIRI, intraperitoneal injections of Cornus mas Extract (CME) were administered for 14 days in a dosedependent manner (30, 60, and 120 mg/kg body weight). The effects of CME on learning and memory recovery were evaluated using a shuttle box behavioral test. Two weeks following CIRI, several factors of oxidative stress, such as nitrite (NO2-), Ferric ion Reducing Antioxidant Power (FRAP), and Malondialdehyde (MDA), were measured in the hippocampal tissues and serum. Anti-inflammatory genes, such as miR-125b, and the target genes (TNF-α and iNOS) were evaluated via real-time PCR assay. Additionally, neural damage in the CA1 and CA3 regions of the hippocampus was assessed using Hematoxylin and Eosin (H&amp;E) staining. Results: The avoidance time in the shuttle-box behavior test supported our finding that CME exhibited improved fear memory. Furthermore, it increased the CA1 and CA3 hippocampal post-stroke pyramidal cell layers. Levels of NO2- and MDA were decreased, and FRAP was considerably increased in both the hippocampus and serum by CME. Additionally, CME increased miR-125b expression, while modulating TNF-α and iNOS production in the hippocampal regions. Conclusion: Based on our findings, we can conclude CME to possess antioxidant and antiinflammatory properties, which confer neuroprotective potential against CIRI, thereby protecting neurons from ischemic death.

Improving the functional components and biological activities of navel orange juice through fermentation with an autochthonous strain Lactiplantibacillus paraplantarum M23

The fermentation of navel orange juice with lactic acid bacteria (LAB) has rarely been investigated. In this study, an autochthonous LAB strain isolated from navel orange, Lactiplantibacillus paraplantarum M23, was found to effectively ferment navel orange juice, producing a juice with enhanced functional activities and organoleptic quality. The viable bacterial count in the fermented orange juice remained consistently above 8.51 log CFU/mL throughout the entire 7-day fermentation period. The content of vitamin C (VC), total phenolic content (TPC), total flavonoid content (TFC), and hesperidin in the fermented orange juice increased by a maximum of 28.88, 1.21, 1.13, and 1.16 times, respectively, compared to the unfermented orange juice. The fermented juice exhibited significantly higher antioxidant activity than the unfermented juice, with an increase of up to 255 % and 347 % based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) assays, respectively. This may be attributed to the increase in VC and flavonoids, as demonstrated by Pearson's correlation analysis. Additionally, the fermented orange juice demonstrated improved α-glucosidase inhibition, anti-MRSA, and anti-glycation activities compared to the unfermented juice. Furthermore, the fermented juice notably reduced the levels of NO and ROS in Raw 264.7 cells without any negative impact on cell viability. The findings of this study may help in the development of nutritious and healthy fermented navel orange juice products, and serve as a reference for the production of fermented beverages from other fruits using autochthonous strains.

Antinociceptive, antineuropathic, and antimigraine-like activities ofFritillariaimperialis L. rich in verticinone on rats: Mechanisms of action

Ethnopharmacological relevanceFritillaria imperialis L. (Fabaceae), commonly known as “Laleh vazhgon”, ethnomedicinally utilized in Iranian traditional medicine to treat joint pain, chronic daily headaches, and back pain. Aim of the studyTo investigate the antinociceptive, anti-neuropathic, and anti-migraine activities of Fritillaria imperialis bulbs essential oil (FIEO) as well as to uncover the potential mechanisms of action involved. Materials and methodsThe antinociceptive activity of FIEO and its main constituent, Verticinone (Vt), was assessed using the formalin-induced paw licking assay. The potential mechanisms of antinociception were investigated through various antagonists. Additionally, their antineuropathic activity was examined using the cervical spinal cord contusion (CCS) technique and the possible role of Stat3 was evaluated using Western blot analysis. The nitroglycerin-induced model (NTG) was also employed for the evaluation of migraine. ResultsFIEO demonstrated significant antinociceptive activity in both phases of the formalin-induced test. However, the FIEO activity was more pronounced effect observed in the second phase. Modulators of the NO-cGMP-K+ channel pathway significantly reversed the antinociceptive activity of FIEO (P < 0.05). Additionally, antagonists of TRPV1, PPARα, dopamine D1, GABAA, and δ-opioid receptors also significantly reversed the antinociceptive effects of FIEO (P < 0.05). In a separate study, both FIEO and Vt were found to attenuate hyperalgesia and mechanical allodynia (P < 0.01) when evaluated using the CCS-induced pain model. Furthermore, FIEO may alleviate migraine behaviors, likely related to the regulation of NO and CGRP levels. ConclusionFIEO exerts an antineuropathic effect through the phosphorylation of Stat3. Furthermore, the antinociceptive activity is partially modulated via the NO-cGMP-K+ channel pathway, as well as the activation of TRPV, PPAR, opioid, and GABA receptors. Vt may be involved in the antinociceptive, antineuropathic, and antimigraine activities induced by FIEO.

Abietane Diterpenoids from the Rhizomes of Kaempferia roscoeana and Their Anti-Inflammatory Activities.

Six new abietane diterpenes, roscoeananes A-F (1-6), along with two known compounds (7-8) were isolated from the rhizomes of Kaempferia roscoeana. The structures of all compounds were elucidated by analysis of spectroscopic data, and the absolute configurations were assigned by a comparison of the theoretical and experimental electronic circular dichroism (ECD) spectra and a comparison with literature values. The unreported compound 5 is an ether-linked dimer of roscoeanane B (2). Most of the isolated compounds were tested for their nitric oxide inhibitory effects in lipopolysaccharide-activated RAW264.7 cells. Among them, roscoeanane A (1) was found to reduce NO levels in murine macrophage cells with an IC50 value of 3.58 ± 0.95 μM and exhibited low cytotoxicity (IC50 > 50 μM).

Biosensors for measuring nitric oxide NO levels in biosubstrates: a systematic analysis

Nitric oxide NO is a signaling molecule involved in numerous physical and pathological processes in biological systems. Highly sensitive sensor materials for measuring NO amounts in vivo in exhaled air and in body fluids (saliva, blood, urine) can be a useful tool in diagnostics and management of patients with bronchopulmonary, cardiovascular, neurological and tumor diseases. Several approaches to measuring NO in biosubstrates (including exhaled air) have been developed: fluorescence/chemiluminescence, electron spin resonance, electrochemical/amperometric (organic and inorganic) and enzymatic/protein sensors. Semiconductors, transition metal nitrides, phthalocyanine complexes, porphyrin and cobalamin derivatives with metals can serve as materials for NO sensors. Creating sensor materials based on vitamin B12 derivatives is an urgent research task in biomedicine. The article systematizes information on using various compounds as materials for NO-sensitive and selective sensors to measure/evaluate NO levels in various biosubstrates.

Exposure of school children to particulate matter and inorganic gaseous pollutants in Hawassa city, Ethiopia.

The detrimental consequences of air pollution on people, particularly vulnerable groups like children, have drawn a lot of attention globally. Studies on the levels and sources of particulate matter (PM2.5 and PM10) and inorganic gaseous pollutants (NO2, CO, and SO2) in primary schools in Africa, including Ethiopia, are scanty. Therefore, the objective of this study was to determine the levels of particulate matter and inorganic gaseous pollutants in primary schools in Hawassa, Ethiopia, and assess potential health risks. The levels of PM2.5 and PM10 were determined using a portable gas monitor device (HoldPeak Laser PM meter, HP 5800D), whereas NO2, CO, and SO2 levels were determined using the Aeroqual Series 500 Portable Air Quality Monitor (Aeroqual Ltd., New Zealand). The levels of PM2.5, PM10, and NO2 in all sampling sites ranged from 11-66.3, 30.8-399.7, and 60.5-152µg/m3, respectively. The levels of PM2.5 and PM10 were found to be above the World Health Organization recommendations in 55% and 85% of the sampling sites, respectively. The hazard quotient (HQ) values for PM10 and PM2.5 ranged from 0.3 to 3.2 and 0.2 to 1.1, respectively. The Air Quality Index (AQI) at 40% and 30% of the outdoor sampling sites was unhealthy for sensitive groups due to exposure to PM2.5 and PM10, respectively. The levels of PM2.5 and PM10, as well as the AQI and HQ values, indicate a poor condition of the air in the schools, especially in the schools near busy traffic roads.

Liuwei Buqi Formula delays progression of chronic obstructive pulmonary disease in rats by regulating the NLRP3/caspase-1/GSDMD pyroptosis pathway

To explore the therapeutic mechanism of Liuwei Buqi (LWBQ) Formula for chronic obstructive pulmonary disease (COPD) in rat models. SD rat models of COPD established by cigarette smoking combined with intratracheal lipopolysaccharide (LPS) instillation and hormone injection were treated with LWBQ Formula by gavage with or without intraperitoneal injection of MCC950 for 3 weeks, starting at the 5th week of modeling. After the treatments, the rats were examined for lung pathologies, lung function, total cell count and white blood cell count in bronchoalveolar lavage fluid (BALF), and serum levels of IL-6, TNF-α, IL-18 and NO. The mRNA expressions of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 in the lung tissue were detected with qRT-PCR. Compared with the normal control rats, the COPD rat models had severe lung pathologies and showed significantly decreased lung function, increased total cell and leukocyte subset counts in BALF, and increased serum levels of IL-6, TNF-α, IL-18 and NO and mRNA expressions of pyroptosis-related proteins in the lung tissue. Treatment of the rat models with LWBQ Formula significantly improved lung pathology and lung function, reduced total cell and leukocyte counts in BALF, and decreased serum levels of the inflammatory factors and expressions of pyroptosis-related proteins in the lung tissue. The combined treatment with MCC950 further improved lung pathology and function in spite of a significant difference, but BALF cell counts, serum inflammatory factor levels and pulmonary expressions of pyroptosis-related proteins were all significantly reduced following the treatment. LWBQ Formula can delay the progression of COPD in rats possibly by inhibiting lung tissue pyroptosis via regulating the NLRP3/caspase-1/GSDMD pathway to reduce inflammatory response and lung damage.

Tetrahydrofurfuryl Nitrate: A New Organic Nitrate Induces Hypotension and Vasorelaxation Without Vascular Tolerance Induction

The development of new organic nitrates is still relevant due to the clinical limitations of their use. Tetrahydrofurfuryl nitrate (NTHF) is a new organic nitrate obtained through a synthetic route of sugarcane. The aim of this research was to investigate the cardiovascular effects promoted by NTHF in rats. Isolated vascular smooth muscle cells (VSMC) were incubated with a specific probe and were analyzed in a flow cytometer to measure the NO concentration after NTHF treatment. Rat superior mesenteric rings were isolated and used for isometric tension recordings and the evaluation of the vasorelaxant activity induced by NTHF. For the in vivo study, polyethylene catheters were implanted into the abdominal aorta and inferior vena cava of the rats (weighing 250–300 g). NTHF increased NO levels in rat VSMCs. In anesthetized rats, NTHF induced hypotension and bradycardia after intravenous administration. These effects were attenuated after the administration of a sGC inhibitor, methylene blue. In the phenylephrine pre-contracted superior mesenteric artery of rats, NTHF (1 pM–10 μM) induced concentration-dependent vasodilatation in both the intact and removed endothelium. Furthermore, in the presence of NO° scavenging (C-PTIO and HDX) or ODQ, a sGC inhibitor, the vasorelaxation induced by NTHF was decreased. NTHF tolerance was evaluated in mesenteric artery rings previously exposed with isolated concentrations of the new organic nitrate. The vasorelaxant effect was not modified by exposure to nitrate. These results demonstrated that NTHF induced hypotension and bradycardia in vivo and a vasorelaxant effect with the participation of the NO-sGC-PKG pathway and triggering calcium-activated K+ channels without vascular tolerance induction.

Solid-State Gas Sensors with Ni-Based Sensing Materials for Highly Selective Detecting NOx.

Precise monitoring of NOx concentrations in nitric oxide delivery systems is crucial to ensure the safety and well-being of patients undergoing inhaled nitric oxide (iNO) therapy for pulmonary arterial hypertension. Currently, NOx sensing in commercialized iNO instruments predominantly relies on chemiluminescence sensors, which not only drives up costs but also limits their portability. Herein, we developed solid-state gas sensors utilizing Ni-based sensing materials for effectively tracking the levels of NO and NO2 in the NO delivery system. These sensors comprised of NiO-SE or (NiFe2O4 + 30 wt.% Fe2O3)-SE vs. Mn-based RE demonstrated high selectivity toward 100 ppm NO under the interference of 10 ppm NO2 or 3 ppm NO2 under the interference of 100 ppm NO, respectively. Meanwhile, excellent stability, repeatability, and humidity resistance were also verified for the proposed sensors. Sensing mechanisms were thoroughly investigated through assessments of adsorption capabilities and electrochemical reactivity. It turns out that the superior electrochemical reactivity of NiO toward NO, alongside the NO2 favorable adsorption characteristics of (NiFe2O4 + 30 wt.% Fe2O3), is the primary reason for the high selectivity to NOx. These findings indicate a bright future for the application of these NOx sensors in innovative iNO treatment technologies.

Oxidative stress model of lipopolysaccharide combined with thrombin inducing in broiler chicks.

Lipopolysaccharides (LPS) are commonly used to construct inflammation models. However, poultry have a certain degree of tolerance to LPS due to the lack of thrombin XI and XII in their bodies. Thrombin activation produces clotting factors that can cleave prothrombin to form thrombin. The purpose of this study was to construct a chick oxidative stress model used different concentrations of LPS combined with thrombin in order to screen for the optimal concentration for constructing the oxidative stress model, and to explore the effects of this stimulus on various indicators of chicks. Eighty-one young chicks (4-days-old) were randomly divided into three groups with 27 chicks per group where each group contained 3 replicates with 9 birds each: a control group (physiological saline), a low-dose group (LPS 5 mg/kg thrombin 150 U/kg), and a high-dose group (LPS 10 mg/kg thrombin 300 U/kg). The results indicated that compared with the control group, the low-dose group and the high-dose group significantly increased the content of Malondialdehyde (MDA) in serum and reduced the content of T-AOC, GSH-PX and SOD, respectively. Meanwhile, the levels of NO and inflammatory factors IL-1β, IL-6 and TNF-α TNF-α in the liver were significantly increased in the low-dose and high-dose groups compared with the control group, respectively. Liver and thymus tissue sections from the low- and high-dose groups showed hemorrhage, hemolysis, and a small amount of exudation. In terms of inflammatory effect, the serum MDA content and the levels of NO, IL-1β, IL-6 and TNF-α factors in the liver were significantly increased in the low-dose group compared with the high-dose group. On histopathological observation, tissue damage was more pronounced in the low-dose group than in the high-dose group. In conclusion, LPS combined with thrombin could induce oxidative stress in chicks and the pathological changes of the low-dose effect are more pronounced.

Spatio-Temporal Analysis of Air Pollution in Sharjah City Pre-to-Post COVID-19 Lockdown

This study presents an analysis of O3, NO2, and PM10 variations in Sharjah City, UAE, from 2018 to 2021. Data from monitoring stations across the city showed consistent daily, weekly, and monthly trends. Ozone and NO2 were inversely related, with O3 increasing and NO2 decreasing from noon to sunset, and vice versa afterward. Weekends exhibited a weekend effect, with high O3 and low NO2 levels. Winters had high NO2 and low O3 levels, while summers showed the opposite trend. Urban and industrial stations had higher NO2 and lower O3 levels compared to sub-urban and rural stations. PM10 levels peaked in the afternoon to late evenings and decreased during nights and early mornings. They were lowest on weekends and highest at the start of the weeks, with July as the peak and December as the lowest month for PM10. During the COVID-19 restrictions of 2020-2021, O3, NO2, and PM10 levels significantly decreased compared to 2018-2019. Higher winds correlated with higher O3 and PM10 levels and lower NO2 levels. This study provides the first documentation of Sharjah’s air quality spatiotemporal variations pre-to-post COVID-19 restrictions using ground measurements.

Hydrogen sulfide enhances the disease resistance of ginger to rhizome rot during postharvest storage through modulation of antioxidant response and nitric oxide-mediated S-nitrosylaion

Postharvest pathogenic infestation leads to the quality deterioration in ginger industry. Hydrogen sulfide (H2S), as an emerging potential postharvest protectant, could enhance disease resistance. This study investigated the antifungal role of H2S against Fusarium solani during ginger postharvest storage. The results showed that H2S restricted widespread infection by F. solani in gingers and have direct antimicrobial activity against F. solani in vitro, inhibiting mycelial growth and spore germination. H2S improved endogenous H2S accumulation, increased the activities of POD, CAT and SOD, and facilitated the removal of excess ROS. It also promoted the lignin, total phenolic and flavonoid contents, while boosting the activities of PAL, C4H and 4CL, and up-regulating the expression of ZoPAL, ZoC4H and Zo4CL. Moreover, H2S increased endogenous NO levels through the NR and NOS pathways. Notably, the endogenous SNO content was increased, the GSNOR activity as well as expression of GSNOR were down-regulated by H2S treatment. These effects were reversed by hypotaurine (HT), a scavenger of H2S. Together, these results indicated that H2S induces the disease resistance in postharvest ginger storage via enhancing antioxidant and defense capacity, regulating phenylpropane metabolism, inducing NO production and mediating NO-dependent S-nitrosylation modification. These results provide guidance for the application of H2S during the storage of ginger.

Design, synthesis and molecular docking studies of tailored coumarin and chromone derivatives for use as anti-Alzheimer agents

Two new series of coumarin hydrazide and chromone pyrazole derivatives were designed and synthesized to evaluate their in vitro and in vivo anti-Alzheimer activity. All the derivatives were tested for their ability to inhibit cholinesterases. Compound 14 displayed the highest in vitro inhibitory activity against acetylcholinesterase and butyrylcholinesterase with IC50 values of 3.31 µM and 1.60 µM, respectively. The in vivo study revealed the capability of the promising derivative to cause a decline in acetylcholinesterase levels, ameliorate the antioxidative activities of TAC and GSH, decrease the levels of MDA and NO, and down regulate that of MAP-TAU and APP. Moreover, the examination of the AD-brain regions treated with the synthetic compound 14 revealed an improvement of AD histological hallmarks. Molecular modeling of compound 14 demonstrated the interactions of the derivative with the key amino acids in AChE active site. A molecular dynamic simulation and an in silico pharmacokinetic study were conducted as well.