Nitric Oxide Concentration Research Articles

Central angiotensin-(1–7) attenuates hypoglycemia in sepsis-like conditions via reducing systemic and hepatic inflammation

Sepsis is understood as the result of initiating systemic inflammation derived from an inadequate host response against pathogens. In its acute phase, sepsis is marked by an exacerbated reaction to infection, tissue damage, organ failure, and metabolic dysfunction. Among these, hypoglycemia, characterized by disorders of the gluconeogenesis pathway, is related to one of the leading causes of mortality in septic patients. Recent research has investigated the involvement of sympathetic efferent neuroimmune pathways during systemic inflammation. These pathways can be stimulated by several centrally administered drugs, including Angiotensin-(1–7) (Ang-(1–7)). Therefore, the present study aims to evaluate the effects of central treatment with Ang-(1–7) on hypoglycemia during endotoxemia. For this, male Wistar Hannover rats underwent stereotaxic surgery for intracerebroventricular (i.c.v.) administration of Ang-(1–7) and cannulation of the jugular vein for lipopolysaccharide (LPS) injection. Our results demonstrate that LPS was capable of inducing hypoglycemia and that prior central treatment with Ang-(1–7) attenuated this effect. Our data also show that Ang-(1–7) reduced plasma concentrations of TNF-α, IL-1β, IL-6, and nitric oxide, in addition to the decrease and increase of hepatic IL-6 and IL-10 respectively, in animals subjected to systemic inflammation by LPS, resulting in the reduction of systemic and hepatic inflammation, thus attenuating the deleterious effects of LPS on phosphoenolpyruvate carboxykinase protein content. In summary, the data suggest that central treatment with Ang-(1–7) attenuates hypoglycemia induced by endotoxemia, probably through anti-inflammatory action, leading to reestablishing hepatic gluconeogenesis.

Ferrocene probe-assisted fluorescence quenching of PEI-carbon dots for NO detection and the logic gates based sensing of NO enabled by trimodal detection

Our research demonstrates the effectiveness of fluorescence quenching between polyethyleneimine functionalised carbon dots (PEI-CDs) and cyclodextrin encapsulated ferrocene for fluorogenic detection of nitric oxide (NO). We confirmed that ferrocene can be used as a NO probe by observing its ability to quench the fluorescence emitted from PEI-CDs, with NO concentrations ranging from 1 × 10–6 M to 5 × 10–4 M. The photoluminescence intensity (PL) of PEI-CDs decreased linearly, with a detection limit of 500 nM. Previous studies have shown that ferrocene is a selective probe for NO detection in biological systems by electrochemical and colorimetric methods. The addition of fluorogenic NO detection using ferrocene as a probe enables the development of a three-way sensor probe for NO. Furthermore, the triple mode NO detection (electrochemical, colorimetric, and fluorogenic) with ferrocene aids in processing sensing data in a controlled manner similar to Boolean logic operations. This work presents key findings on the mechanism of fluorescence quenching between ferrocene hyponitrite intermediate and PEI-CDs, the potential of using ferrocene for triple channel NO detection as a single molecular entity, and the application of logic gates for NO sensing.

Enhancing the antioxidant and anti-inflammatory potentials of mulberry-derived postbiotics through submerged fermentation with B. subtilis H4 and B. amyloliquefaciens LFB112

Mulberry-derived postbiotics (MDP) have been scientifically proven to possess beneficial properties for human health, making them potential nutraceuticals. This study aims to enhance the antioxidant and anti-inflammatory effect of MDP via submerged fermentation with Bacillus subtilis H4 (H4) and Bacillus amyloliquefaciens LFB112 (LFB112) bacterial strains. Our results demonstrated compelling evidence that the combination of two strains with the optimized time (24 h), inoculum size (8%), and substrate size (10%) significantly increased the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activities. When compared to the non-fermented mulberry (NFM), the MDP with the above-optimized conditions showed substantially higher antioxidant activities such as DPPH, 2,2′-Azino-bis (3-ethylebenzothiazoline-6-sulfonic acid) (ABTS), hydroxyl scavenging activities, and reducing power capabilities. Moreover, the MDP showed a significant decrease in the lipopolysaccharides (LPS)-induced reactive oxygen species (ROS) generated in RAW264.7 cells. The antibacterial assays such as minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) showed that MDP possesses antibacterial activity against various pathogenic bacterial strains with the lowest MIC recorded as 32.5 mg/ml against S. pullorum CVCC519, while the highest MIC observed was 40 mg/ml against P. aeruginosa. The lowest and highest MBCs observed were 40 and 55 mg/ml against S. aureus ATCC43300 and S. pullorum CVCC519 respectively. Furthermore, the MDP showed good ant-inflammatory activities by significantly reducing the nitric oxide (NO) concentration (p<0.0001) and mRNA expression of the proinflammatory cytokines in response to the LPS-induced inflammation in the RAW264.7 macrophage cell line. To sum up, our findings indicate that MDP as a novel postbiotics can be utilized both as a functional food and a safe feed additive, possibly benefiting gut and metabolic health.

L-Histidine attenuates NEFA-induced inflammatory responses by suppressing Gab2 expression

Non-esterified fatty acids (NEFAs), key to energy metabolism, may become pathogenic at elevated levels, potentially eliciting immune reactions. Our laboratory's findings of reduced L-histidine in ketotic states, induced by heightened NEFA concentrations, suggest an interrelation with NEFA metabolism. This observation necessitates further investigation into the mitigating role of L-histidine on the deleterious effects of NEFAs. Our study unveiled that elevated NEFA concentrations hinder the proliferation of Bovine Mammary Epithelial Cells (BMECs) and provoke inflammation in a dose-responsive manner. Delving into L-histidine's influence on BMECs, RNA sequencing revealed 2124 genes differentially expressed between control and L-histidine-treated cells, with notable enrichment in pathways linked to proliferation and immunity, such as cell cycle and TNF signaling pathways. Further analysis showed that L-histidine treatment positively correlated with an increase in EdU-555-positive cell rate and significantly suppressed IL-6 and IL-8 levels (p < 0.05) compared to controls. Crucially, concurrent treatment with high NEFA and L-histidine normalized the number of EdU-555-positive cells and cytokine expression to control levels. Investigating the underlying mechanisms, Gab2 (Grb2-associated binder 2) emerged as a central player; L-histidine notably reduced Gab2 expression, while NEFA had the opposite effect (p < 0.05). Gab2 overexpression escalated nitric oxide (NO) production and IL6 and IL8 expression. However, L-histidine addition to Gab2-overexpressing cells resulted in NO concentrations indistinguishable from controls. Our findings collectively indicate that L-histidine can counteract NEFA-induced inflammation in BMECs by inhibiting Gab2 expression, highlighting its therapeutic potential against NEFA-related metabolic disturbances.

Hemp seed protein and its hydrolysate compared with casein protein consumption in adults with hypertension: a double-blind crossover study

BackgroundThe effects of consuming hemp seed protein (HSP) as well as its hydrolysate-derived bioactive peptide (HSP+) on blood pressure (BP) has not, to our knowledge, been investigated in humans. ObjectivesWe aimed to investigate how consumption of HSP and its hydrolysate modulates 24-h systolic (SBP) and diastolic BP (DBP) and plasma biomarkers of BP compared with casein. MethodsIn a double-blind, randomized, crossover design trial, 35 adults who had mild hypertension with SBP between 130 and 160 mmHg and DBP ≤110 mmHg were recruited. Participants were randomly assigned to varying sequences of 3 6-wk treatments, 50 g casein/d, 50 g HSP/d, or 45 g HSP plus 5 g HSP-derived bioactive peptides/d (HSP+), separated by a 2-wk washout period. Treatment effects were assessed with a linear mixed model with repeated measures. ResultsCompared with casein, after HSP+ consumption, 24-h SBP and 24-h DBP decreased from 135.1 and 80.0 mmHg to 128.1 ± 1.6 (P < 0.0001) and 76.0 ± 1.4 mmHg (P < 0.0001), respectively, whereas these values were 133.5 ± 1.6 and 78.9 ± 1.4 mmHg after HSP consumption (P < 0.0001). There were no differences between the HSP and HSP+ consumption in plasma angiotensin-converting enzyme (ACE) activity, renin, or nitric oxide (NO) concentrations. However, these 2 treatments were able to lower both ACE and renin activities and raise NO concentration in plasma compared with casein. ConclusionsThese results suggest that hemp protein consumption, as well as in combination with bioactive peptides, may have a role in the dietary management of hypertension.This trial was registered at clinicaltrials.gov as NCT03508895.

Assessment of single and combined administration of ubiquinone and lactoferrin on histopathology, ultrastructure, oxidative stress, and WNT4 expression gene induced by thioacetamide on hepatorenal system of adult male rats

BackgroundHepatorenal syndrome is a life-threatening medical complication of liver cirrhosis. Hepatic cirrhosis is commonly accompanied by rapid failure of renal functions. Thioacetamide (TAA) is a potent hepatotoxin and a class 2-type carcinogen. Ubiquinone (Coq10) and lactoferrin (LF) are potent antioxidants with antifibrotic and antiinflammatory effects. However, whether Coq10 and LF reduce the hepatorenal injury induced by TAA remains unclear. Here, we investigated the potential protective effect of both/or Coq10 and LF in ameliorating TAA-induced hepatorenal injury and the role of WNT4 gene expression in detecting TAA-induced renal injury in rats. Seventy healthy and mature male Sprague Dawley rats, weighting (200 g ± 20 g) and aging (4–6) weeks were randomly divided into seven groups (n = 10): control, Coq10, LF, TAA, TAA + Coq10, TAA + LF, and TAA + Coq10 + LF. The hepatorenal injury was induced through intraperitoneal (i.p.) injection of TAA (150 mg/kg/twice/weekly) for nine weeks. Coq10 (10 mg/kg/day) and LF (200 mg/kg/day) were orally administered for nine weeks.ResultsTAA induced marked hepatorenal damage, evident by the significant increase in the alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (SCr) activities, and the blood urea nitrogen (BUN) level. Besides, the significant increases in concentrations of malondialdehyde (MDA) and nitric oxide (NOx) together with significant decreases in the activities of catalase (CAT) and superoxide dismutase (SOD). The histopathological analysis of the TAA group showed obvious fibrosis, steatosis, and inflammation of the hepatic parenchyma as well as severe glomerular and tubular damage of the renal parenchyma. In addition, TAA induced marked ultrastructural alterations and up-regulation in the expression of the WNT4 gene in the kidney. Meanwhile, the biochemical, histopathological, and ultrastructural alterations were significantly decreased with significant down-regulation in the expression of WNT4 in the groups exposed to TAA and treated with Coq10 and LF.ConclusionOur data suggested that Coq10 and LF could have protective effects on TAA hepatorenal damage, through improving the hepatic and renal functions, reduction of oxidative stress, structural and ultrastructural alterations, besides down-regulation in the expression of WNT4.

Nitric Oxide Concentration: A New Data Set Derived From SABER Measurements

AbstractVertical profiles of nitric oxide (NO) concentration are derived between 120 and 250 km using updated NO emission rates measured by Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the NASA Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite. The Naval Research Laboratory Mass Spectrometer Incoherent Scatter Radar (MSIS) 2.1 model is used to provide the required parameters of temperature, atomic oxygen number density, and molecule oxygen number density needed to derive the NO concentrations using a non‐local thermodynamic equilibrium (non‐LTE) model. The SABER NO concentration shows a significant correlation with solar activity with larger peak NO concentrations and higher altitude extent during solar maximum years compared to those during the solar minimum years. The SABER NO agrees well with the MSIS 2.1 NO at altitudes above 120 km for all latitudes, while the pronounced SABER‐MSIS NO discrepancy below 120 km is likely due to the temperature underestimation by MSIS 2.1. A detailed error analysis is presented and considers systematic and random errors in all the terms in the non‐LTE model used to derive the NO concentration. Random error in MSIS 2.1 temperature and atomic oxygen dominates the uncertainty in single NO profiles above 120 km. We estimated a systematic error up to ∼36% between 120 and 250 km during solar maximum years.

3-Fucosyllactose-mediated modulation of immune response against virus infection

Viral pathogens, particularly influenza and SARS-CoV-2, pose a significant global health challenge. Given the immunomodulatory properties of human milk oligosaccharides, in particular 2′-fucosyllactose and 3-fucosyllactose (3-FL), we investigated their dietary supplementation effects on antiviral responses in mouse models. This study revealed distinct immune modulations induced by 3-FL. RNA-sequencing data showed that 3-FL increased the expression of interferon receptors, such as Interferon Alpha and Beta Receptor (IFNAR) and Interferon Gamma Receptor (IFNGR), while simultaneously downregulating interferons and interferon-stimulated genes, an effect not observed with 2′-fucosyllactose supplementation. Such modulation enhanced antiviral responses in both cell culture and animal models while attenuating pre-emptive inflammatory responses. Nitric oxide concentrations in 3-FL-supplemented A549 cells and mouse lung tissues were elevated exclusively upon infection, reaching 5.8- and 1.9-fold increases over control groups, respectively. In addition, 3-FL promoted leukocyte infiltration into the site of infection upon viral challenge. 3-FL supplementation provided protective efficacy against lethal influenza challenge in mice. The demonstrated antiviral efficacy spanned multiple influenza strains and extended to SARS-CoV-2. In conclusion, 3-FL is a unique immunomodulator that helps protect the host from viral infection while suppressing inflammation prior to infection.

BIOCHEMICAL INDICATORS OF GASTRIC JUICE IN INCOMPETENCE OF THE PHYSIOLOGICAL GASTRIC CARDIA

Aim. This study aimed to evaluate the biochemical characteristics of gastric juice in cases incompetence of the physiological cardia (IPC) at the gastroesophageal junction. Methods. Gastric juice samples were collected from 42 patients diagnosed with hiatal hernia (HH) at the State Institution "Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine". Patients were classified into type I (sliding) HH (n=26) and type II (paraesophageal) HH (n=16), with a control group of healthy volunteers (n=9). Results. Analysis included pH, pepsin concentration, bile acids, total calcium and stable metabolites of nitric oxide (NOx). In type I HH, gastric juice showed increased pH (3.73±0.49) and elevated pepsin concentration (1.33±0.22 mg/ml) compared to controls (p&lt;0.01 and P&lt;0.05 respectively), indicating hypoacidity and hyperfunction of chief cells. Type II HH exhibited pH levels (2.34±0.72) similar to controls and no significant difference in pepsin concentration. NOx levels in type I HH were lower (P&lt;0.05) compared to controls, suggesting reduced NOergic system activity. Calcium concentration in gastric juice did not significantly differ between groups. Conclusions. These findings suggest that type I HH is associated with disturbances in gastric secretion regulation, possibly unrelated to duodenogastric reflux. Further investigation is warranted to elucidate the underlying pathophysiological mechanisms.

Exhaled Nitric Oxide Reflects the Immune Reactions of the Airways in Early Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included. Their exhaled NO levels were measured, and the alveolar concentration, the airway compartment diffusing capacity and the airway wall concentration of NO were estimated using the Högman-Meriläinen algorithm. The disease activity was measured using the Disease Activity Score for 28 joints. Serum samples were analysed for anti-CCP2, rheumatoid factor, free secretory component, secretory component containing ACPAs, antibodies against Porphyromonas gingivalis (Rgp) and total levels of IgA, IgA1 and IgA2. Significant negative correlations were found between the airway wall concentration of NO and the number of swollen joints (Rho -0.48, p = 0.004), between the airway wall concentration of NO and IgA rheumatoid factor (Rho -0.41, p = 0.017), between the alveolar concentration and free secretory component (Rho -0.35, p = 0.023) and between the alveolar concentration and C-reactive protein (Rho -0.36, p = 0.016), but none were found for anti-CCP2, IgM rheumatoid factor or the anti-Rgp levels. In conclusion, altered NO levels, particularly its production in the airway walls, may have a role in the pathogenesis of ACPA-positive RA.

Hydrogen-bond tuned conjugated architectures for nitric oxide sensing in single-benzene framework: Advances and mechanistic insights

In contrast to the conventional fluorescence enhancement resulting from the cessation of the photoinduced electron transfer effect upon capturing nitric oxide (NO) by o-phenylenediamine, we found an interesting fluorescence quench within small molecule fluorophores characterized by intramolecular hydrogen bonding. Herein, the integration of a push-pull electron system with intramolecular hydrogen bonding onto an ultra-small fluorophore was employed to fabricate a hydrogen bond-tuned single benzene core fluorescent probe with an exceptional fluorescence quantum yield of 26 %, denoted as HSC-1. By virtue of its small size and low molecular weight (mere 192 g/mol), it demonstrated superior solubility and biocompatibility. Given the optimized conditions, HSC-1 manifested extraordinary linearity in detecting NO concentrations ranging from 0.5 to 60 μM, with an outstanding detection limit of 23.8 nM. Theoretical calculations unraveled the photophysical properties of hydrogen bonding-related probe molecules and highlighted the NO sensing mechanism. This pioneering work offers an important platform for the design of small fluorescence probes only with a single benzene core applied to NO sensing, which will potentially emerge as a new frontier in the area.

Fractional exhaled nitric oxide in idiopathic pulmonary arterial hypertension and mixed connective tissue disease complicating pulmonary hypertension

BackgroundFractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function.MethodsWe collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient.Results(1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test.ConclusionFeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.

Macrophages, IL-10, and nitric oxide increase, induced by hyperglycemic conditions, impact the development of murine melanoma B16F10-Nex2

Epidemiological studies show a strong correlation between diabetes and the increased risk of developing different cancers, including melanoma. In the present study, we investigated the impact of a streptozotocin (STZ)-induced hyperglycemic environment on B16F10-Nex2 murine melanoma development. Hyperglycemic male C57Bl/6 mice showed increased subcutaneous tumor development, partially inhibited by metformin. Tumors showed increased infiltrating macrophages, and augmented IL-10 and nitric oxide (NO) concentrations. In vivo neutralization of IL-10, NO synthase inhibition, and depletion of macrophages reduced tumor development. STZ-treated TLR4 KO animals showed delayed tumor development; the transfer of hyperglycemic C57Bl/6 macrophages to TLR4 KO reversed this effect. Increased concentrations of IL-10 present in tumor homogenates of hyperglycemic mice induced a higher number of pre-angiogenic structures in vitro, and B16F10-Nex2 cells incubated with different glucose concentrations in vitro produced increased levels of IL-10. In summary, our findings show that a hyperglycemic environment stimulates murine melanoma B16F10-Nex2 primary tumor growth, and this effect is dependent on tumor cell stimulation, increased numbers of macrophages, and augmented IL-10 and NO concentrations. These findings show the involvement of tumor cells and other components of the tumor microenvironment in the development of subcutaneous melanoma under hyperglycemic conditions, defining novel targets for melanoma control in diabetic patients.

Effects of Phytosterol Ester Supplementation on Egg Characteristics, Eggshell Ultrastructure, Antioxidant Capacity, Liver Function and Hepatic Metabolites of Laying Hens during Peak Laying Period.

The aim of this experiment was to investigate the effects of dietary Phytosterol Ester (PSE) supplementation on egg characteristics, eggshell ultrastructure, antioxidant capacity, liver function, hepatic metabolites, and its mechanism of action in Hy-Line Brown laying hens during peak laying period. A total of 256 healthy Hy-Line Brown laying hens were randomly allocated into four groups. The hens in the control group were fed a basal diet, while those in the experimental groups were fed a basal diet further supplemented with 10, 20, and 40 mg/kg PSE, respectively. It was found that the addition of 20 mg/kg and 40 mg/kg PSE to the diets increased egg weight, but decreased egg breaking strength (p < 0.05). The addition of PSEs to the diets increased albumen height and Haugh unit in all experimental groups (p < 0.05). Electron microscopic observation revealed that the mammillary thickness increased significantly at doses of 20 and 40 mg/kg, but the total thickness decreased, and the effective thickness also thinned (p < 0.05). The mammillary width narrowed in all experimental groups (p < 0.001). Dietary supplementation with 40 mg/kg PSE significantly increased egg yolk Phenylalanine, Leucine, and Isoleucine levels (p < 0.05). In untargeted liver metabolomic analyses, L-Phenylalanine increased significantly in all experimental groups. Leucyl-Lysine, Glutamyl-Leucyl-Arginine, and L-Tryptophan increased significantly at doses of 10 and 20 mg/kg (p < 0.05), and L-Tyrosine increased significantly at doses of 10 and 40 mg/kg (p = 0.033). Aspartyl-Isoleucine also increased significantly at a dose of 10 mg/kg (p = 0.044). The concentration of total protein in the liver was significantly higher at doses of 20 and 40 mg/kg than that of the control group, and the concentrations of total cholesterol and low-density lipoprotein cholesterol were significantly reduced (p < 0.05). The concentration of triglyceride and alkaline phosphatase were significantly reduced in all experimental groups (p < 0.05). Steatosis and hemorrhage in the liver were also improved by observing the H&E-stained sections of the liver. Concerning the antioxidant capacity in the liver, malondialdehyde concentration was significantly reduced (p < 0.05) at a dose of 40 mg/kg. In the ovary, malondialdehyde and nitric oxide concentrations were significantly reduced (p < 0.001). In all the experimental groups, plasma nitric oxide concentration was significantly decreased while superoxide dismutase was significantly increased, and total antioxidant capacity concentration was significantly increased (p < 0.05) in the 10 mg/kg and 40 mg/kg doses. Metabolomics analyses revealed that PSEs play a role in promoting protein synthesis by promoting Aminoacyl-tRNA biosynthesis and amino acid metabolism, among other pathways. This study showed that the dietary addition of PSEs improved egg characteristics, antioxidant capacity, liver function, and symptoms of fatty liver hemorrhagic syndrome in Hy-Line Brown laying hens at peak laying stage. The changes in liver metabolism suggest that the mechanism of action may be related to pathways such as Aminoacyl-tRNA biosynthesis and amino acid metabolism. In conclusion, the present study demonstrated that PSEs are safe and effective dietary additives as an alternative to antibiotics.

Phytochemical and Anti-inflammatory Activities of Oxytropis aciphylla

Background: The objective of this research is to explore the phytochemical constituents and the potential anti-inflammatory properties of the herb Oxytropis aciphylla. Methods: From the ethyl acetate and n-butanol fractions derived from the 70% ethanol extract of O. aciphylla, a total of 17 distinct chemical entities were extracted and subsequently identified. Utilizing network pharmacology, the study predicted the possible anti-inflammatory targets and mechanisms of action of O. aciphylla. The study assessed the anti-inflammatory impact of O. aciphylla extract on RAW 264.7 (a murine macrophage cell line) cells induced with lipopolysaccharide (LPS) by quantifying the concentrations of nitric oxide (NO), tumor necrosis factor-alpha (TNF- α), and interleukin-6 (IL-6). Results: The isolated compounds included 12 flavonoids, two triterpenoids, one fatty acid, and two sterols. These specifically comprise apigenin, luteolin, kaempferol, isorhamnetin, naringenin, eriodictyol, dihydrokaempferol, butein, 7,4’-homoisoflavanone, apigenin-7- O- β-D-glucopyranoside, isorhamnetin-3- O- β-D-gentiobioside, rutin, azukisapogenol, 3- O-[ β-D-glucopyranosyl(1↓2)- β-D-glucuronopyranosyl] azukisapogenol methyl ester, tetracosanoic acid, daucosterol, and β-sitosterol. Network pharmacology analysis suggested that O. aciphylla may exert its anti-inflammatory effects through multiple components, targets, and pathways, such as kaempferol, apigenin, luteolin, AKT1, SRC, TNF, PTGS2, EGFR, MAPK, PI3K-Akt, VEGF, HIF-1, and TNF signaling pathways. The extract of O. aciphylla was found to markedly reduce the levels of NO, TNF- α, and IL-6 in RAW 264.7 cells that were stimulated with LPS, demonstrating a correlation with the dosage administered. Conclusion: The investigation uncovered, for the first time, the phytochemical constituents and the mechanisms underlying the anti-inflammatory effects of O. aciphylla. These findings lay the groundwork for the scientific development and application of this botanical species as a natural remedy for inflammation.

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

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

Multiparameter gas sensor based on UV-SFR combined with wavelet transform-neural network at ppb level

Abnormal concentrations of nitric oxide (NO), ammonia (NH3), carbon disulfide (CS2) and sulphur dioxide (SO2) in exhaled breath are closely associated with diseases in specific organs of the body. Meanwhile, the above gases are also common pollutants in the atmosphere, and effective online detection of them plays a key role in disease prevention and environmental pollution prevention. This study reports a multiparameter gas sensor system based on the combination of ultraviolet segmented fitting reduction (UV-SFR) and wavelet transform-neural network (WT-NN) model for simultaneous online detection of the concentrations of NO, NH3, CS2 and SO2. Firstly, to avoid the occurrence of spectral baseline drift and absorption peak intensity reduction, a UV-SFR method is proposed for the discrete single peak type absorption spectra contained in the UV spectra. Our method can remove the slow change absorption induced by other factors, and ultimately obtain the differential absorption spectra of the gas mixtures. Then, the WT is used to denoise the differential absorption spectra of the gas mixtures. Next, for the presence of severe spectral line overlap in gas mixtures, the NN model is built based on the denoised spectral data. Finally, transfer learning is introduced into NN to improve the detection accuracy. The experimental results show that the sensor system can reliably achieve simultaneous online detection of NO, NH3, CS2, and SO2 at ppb level, and the average absolute errors of their measurements are 0.96 ppb, 1.27 ppb, 0.76 ppb and 0.97 ppb, with measurement accuracies of 3.5 %, 0.8 %, 0.5 % and 0.9 %, respectively.

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

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

The influence of environmental change and seasons on the sperm quality of breeding boars after relocation

This study aimed to determine the impact of relocation as a potential stress factor on the reproductive properties of breeding boars, as well as the impact of the new environment on the quantity and quality of the semen obtained during different seasons. At the beginning of spring, 16 breeding boars (Large White (n=3), German Landrace (n=4), Swedish Landrace (n=6) and Pietrain (n=3)) were relocated from old to new housing conditions and exposed to loading, transport, unloading, and rehousing in a new environment. They had the same conditions of feeding, care, sexual exploitation and keeping, before and after relocation. The health status of all breeding boars was carefully monitored and controlled. No significant differences were observed in the total and average number of doses produced between seasons. There was a significantly higher value of total ejaculate volume and density during the spring compared to the values obtained in other seasons (P&lt;0.01). Differences in the average percentage of mobility between autumn and winter were not significant (P=0.983), as in spring and summer (P=0.737). Ventilation rate, gas concentrations of ammonia, nitrous oxide and carbon dioxide in the boar enclosure were similar before and after relocation. Two days after relocation, one boar (ID 172) showed signs of illness and was treated, but his sperm was rejected due to sperm agglutination and reduced motility, so he was culled. Individual analysis of the production indicators showed that there was no significant change in the spermatogenesis of healthy boars, even though they were relocated.

Determination of Malondialdehyde, Nitric Oxide, Reduced Glutathione, Sialic Acid and Ceruloplasmin Levels in Sheep Liver Tissue With Hydatic Cyst

Cystic echinococcosis is a prevalent helminth-zoonosis that poses a significant threat to human and animal health worldwide. Although it typically shows an asymptomatic clinical course, it has been reported to cause many damages and biochemical changes in tissues and organism. The aim of this study was to investigate the concentrations of nitric oxide (NO), reduced glutathione (GSH), malondialdehyde (MDA), ceruloplasmin (Cp), and total sialic acid (TSA) in sheep liver tissue affected by cystic echinococcosis. The study was carried out on sheep between 4-5 years of age brought to the slaughterhouse in the Igdir territory. The livers were examined post-mortem for cystic echinococcosis and cystic structures. Sheep liver tissues that tested positive for protoscolex were designated as the ‘infected group’, while healthy sheep liver tissues without lesions were assigned to the ‘control group’. The results showed significantly higher levels of NO, MDA, Cp and TSA in the infected group compared to the control group (p&amp;lt;0.05), while GSH levels were significantly lower (p&amp;lt;0.05). These findings indicate that cystic echinococcosis in sheep is closely associated with mechanisms of inflammation, oxidative stress, and tissue damage. Moreover, our study provides insights into the oxidative response of cystic echinococcosis in liver tissue and enhances our understanding of the disease’s pathogenesis.