Nitric Oxide Levels Research Articles

Correlation Between Serum microRNA-18a Level and Endothelial Function and Prognosis in Female Coronary Heart Disease Patients.

The aim was to analyze the correlation between serum microRNA (miR)-18a level, endothelial function, and prognosis in female coronary heart disease (CHD) patients. One hundred sixtyfemale patients admitted to our hospital for the first occurrences of chest pain and tightness were divided into CHD and non-CHD groups based on the coronary angiography results. Clinical data, laboratory indexes, serum miR-18a level, and endothelial function [flow-mediated dilation (FMD) function, endothelin 1 (ET-1), and nitric oxide (NO)] were compared. There were no significant differences in clinical data (except CHD family history) between 2 groups. Coronary heart disease group had significantly lower levels of NO and FMD, while significantly higher levels of miR-18a and ET-1 than non-CHD group (P <.05). Pearson correlation showed that serum miR-18a level was positively correlated with ET-1 (r = 0.492, P <.001), and negatively correlated with NO and FMD (r = -0.504, -0.307, P <.001). The receiver operating characteristic) curve showed that the area under the curve of serum miR-18a level in predicting the occurrence of CHD in women was 0.878 (95% CI: 0.828-0.928). Compared with good prognosis group, poor prognosis group had signifi-cantly lower NO, and FMD levels, while higher proportions of acute coronary syndrome, multivessel disease, miR-18a, and ET-1 levels (P <.05). The expression of serum miR-18a in female CHD patients was high, which was related to endothelial function. The increase in serum miR-18a level was a risk factor for the occurrence of MACE in female CHD patients during follow-up, and the serum miR-18a level could effectively predict the occurrence of CHD in female patients.

Aegeline attenuates TNBS-induced colitis by suppressing the NFƙB-mediated NLRP3 inflammasome pathway in mice.

A chronic inflammatory condition of the intestine, ulcerative colitis (UC), is challenging to successfully manage once diagnosed. Currently, available medical therapies for UC exhibit minimal efficacy with unacceptable side effects, while inventive biological agents are expensive and yetnotwell accepted by patients. Discovering more effective and safer treatments to treat UC is therefore essential. One of the primary alkaloids found in Aegle marmelos, aegeline, has anti-inflammatory and antioxidant properties as well as being able to suppress severalpro-inflammatory cytokines responsible for inflammation. The study aimed to investigate the effectiveness of aegeline in alleviating 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis through the NFƙB-mediated NLRP3 inflammasome pathway. Mice were randomly allocated into six groups, Normal control (NC), Model control (MC-TNBS, 2,4,6-trinitrobenzene sulfonic acid), STD (TNBS + sulfasalazine 100mg/kg), AG1, AG2, and AG3 (TNBS + aegeline 5, 10, 20mg/kg) respectively. Physical parameters such as a change in body weight, stool consistency, rectal bleeding, colon length, myeloperoxidase (MPO) levels and nitric oxide (NO) levels, and disease activity index (DAI) were assessed and supporting gene expression studies of various pro-inflammatory cytokines and enzymes were evaluated and histopathological changes observed. Administration of aegeline (10, 20mg/kg) was found to be effective in colon protection by lowering the disease activity score and myeloperoxidase level and improving other physical parameters. Aegeline in high dose significantly downregulated the gene expression of NFƙB, iNOS, COX-2, NLRP3, IL-1β, and IL-18, conferring great anti-inflammatory potential. Suggestive of the findings, aegeline reduced the damage to the colon by downregulating transcriptional genes and enzymes leading to inflammation and mitigated TNBS-induced colitis probably through the NFƙB-mediated NLRP3 inflammasome pathway.

Harmine exhibits anti-apoptotic properties and reduces diabetes-induced testicular damage caused by streptozotocin in rats.

Diabetes mellitus induces fertility problems in men, mainly because of increased free radicals. Natural resources are effective for male infertility treatment. This study investigated the effects of harmine, an alkaloid available in Peganum harmala L., on the male reproductive system of diabetic rats. We divided 32 rats into four groups, and eight were randomly placed in each group. For diabetes induction, the animals received 50 mg/kg of streptozotocin intraperitoneally. After 1 week, animals received 15 mg/kg of harmine (28 days; intraperitoneal). Histopathological examinations, serum levels of male hormones, levels of nitric oxide (NO) and malondialdehyde (MDA) in the testes, total antioxidant capacity (TAC), insulin serum levels, fasting blood glucose levels, the apoptotic index, and semen analysis were assessed. The diabetes group exhibited morphological changes in testicular tissue, significant decreases in the diameter of the seminiferous tubule, the Johnsen score, testosterone, luteinizing hormone, follicle-stimulating hormone, insulin serum levels, and TAC in testicular tissue (p<0.01). Harmine treatment ameliorated the morphological changes in the testes and improved sperm parameters relative to the diabetes group (p<0.05). The NO and MDA levels in the testes, fasting blood glucose serum levels, and apoptotic index parameters were significantly elevated in the diabetes group, while in the diabetes+harmine group, these parameters were reduced (p<0.01). Harmine protects testicular tissue and sperm against diabetes-induced damage. This effect of harmine is associated with a rebalancing of the antioxidant capacity that subsequently decreases apoptosis in the testes.

Testing of Anti-EMT, Anti-Inflammatory and Antibacterial Activities of 2′,4′-Dimethoxychalcone

Chalcone (1,3-diaryl-2-propen-1-one) is an α, β-unsaturated ketone that serves as an active constituent or precursor of numerous natural substances, exhibiting a broad spectrum of pharmacological effects. In this study, the classical Claisen–Schmidt condensation method was used to synthesize the chalcone derivative 2′,4′-dimethoxychalcone (DTC) and evaluate its pharmacological activity. By upregulating the expression of the epithelial cell marker E-cadherin and downregulating the expression of the mesenchymal cell marker vimentin, DTC was found to inhibit transforming growth factor-β1 (TGF-β1)-induced epithelial–mesenchymal transition (EMT) process in A549 cells, maintaining the cells’ epithelial-like morphology and reducing the ability of the cells to migrate. Additionally, DTC demonstrated the ability to decrease the expression levels of nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in RAW264.7 cells, suggesting a possible anti-inflammatory effect. Furthermore, DTC was found to exhibit bacteriostatic activity against Staphylococcus aureus (S. aureus), Proteus vulgaris (P. vulgaris), methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans (C. albicans), indicating that this chemical may possess broad-spectrum antibacterial activity.

Fluid dynamics and leukocyte transit in the lymphatic system

Abstract The lymphatic system plays a vital role in maintaining fluid balance in living tissue and serves as a pathway for the transport of antigen, immune cells and metastatic cancer cells. Here, we investigate how the movement of cells through a contracting lymphatic vessel differs from steady flow using a lattice Boltzmann-based computational model. Our model consists of cells carried by flow in a 2D vessel with regularly spaced, bi-leaflet valves that ensure net downstream flow as the vessel walls contract autonomously in response to calcium and nitric oxide levels regulated by stretch and shear stress levels. The orientation of the vessel with respect to gravity, which may oppose or assist fluid flow, significantly modulates cellular motion due to its effect on the contraction dynamics of the vessel, even when the cells themselves are neutrally buoyant. Additionally, our model shows that cells are carried along with the flow, but when the vessel is actively contracting, they move faster than the average fluid velocity. We also find that the fluid forces cause significant deformation of the compliant cells, especially in the vicinity of the valves. Our study highlights the importance of considering the complex, transient flows near the valves in understanding cellular motion in lymphatic vessels.

Parkinson’s disease with anxiety: clinical characteristics and their correlation with oxidative stress, inflammation, and pathological proteins

ObjectiveThis study was performed to explore the differences in the clinical characteristics and oxidative stress indicators, inflammatory factors, and pathological proteins in serum between Parkinson’s disease (PD) with anxiety (PD-A) and with no anxiety (PD-NA) patients, and further correlations among clinical characteristics and above variables were analyzed in PD-A and PD-NA groups.MethodsA total of 121 patients with PD were enrolled in this study and assessed by the Hamilton Anxiety Scale (14 items) (HAMA-14). These patients were divided into PD-A and PD-NA groups according to a cut-off point of 7 of HAMA-14. Demographic variables were collected, and clinical symptoms were assessed by multiple rating scales. The levels of free radicals, inflammatory factors, and pathological proteins in serum were measured by chemical colorimetric method and enzyme-linked immunosorbent assay (ELISA). The differences of above variables were compared between PD-A and PD-NA groups, and the correlations of clinical symptoms with the abovevariables were analyzed in PD-A and PD-NA groups.ResultsThe frequency of PD-A was 62.81%. PD-A group exhibited significantly impaired motor dysfunction and multiple non-motor symptoms, including fatigue, sleep behavior disorder, restless leg syndrome and autonomic dysfunction, and dramatically compromised activities of daily living compard with PD-NA group. PD-A group displayed prominently increasedlevels of hydroxyl radical (·OH) and tumor necrosis factor (TNF)-α, and a decreased nitric oxide (NO) level in serum compared with PD-NA group (P<0.001, P = 0.001, P= 0.027, respectively). ·OH, NO, and TNF-α were identified as the risk factors of PD-A (OR = 1.005, P = 0.036; OR = 0.956, P = 0.017; OR = 1.039, P = 0.033, respectively). In PD patients, HAMA-14 score was significantly and positively correlated with the levels of ·OH and TNF-α in serum (P<0.001, P = 0.002, respectively). In PD-A group, ·OH level was significantly and negatively correlated with Aβ1−42 level, while TNF-α level was significantly and positively correlated with P-tau (S396) level in serum.ConclusionsThe frequency of PD-A is high. PD-A patients present more severe motor dysfunction and multiple non-motor symptoms, and poorer activities of daily living. The increased levels of ·OH and TNF-α levels and the decreased NO level in serum are all associated with more severe anxiety in PD patients.Findings from this study may provide in-depth insights into the clinical characteristics, underlying mechanisms of PD-A, and potential correlations among anxiety, oxidative stress, inflammation, and cognitive decline in PD patients.

Ameliorative Effect of Teucrium polium Extract against Nicotine Induced Liver Toxicity in Swiss Albino Mice

Background: Nicotine can be consumed in many forms, the most common of which is smoking tobacco. Tobacco smoking is a global problem that negatively affects human health. Natural plants are vital antioxidants that may antagonize the toxic effects of smoking. We designed the present study to assess the protective potential of Teucrium polium extract (TPE) on nicotine-induced liver toxicity in male mice. Methods: Twenty-four animals were allocated into four equal groups and daily treated for 21 constitutive days. Control group one received distilled water, group two orally received 100 mg/kg TPE, group three received subcutaneous injections of 2.5 mg/kg nicotine and group four received 100 mg/kg TPE orally then 2.5 mg/kg nicotine subcutaneously after one hour. Result: Nicotine exposure significantly elevated liver enzymes; alanine transaminase (ALT) and aspartate transaminase (AST). The levels of malondialdehyde (MDA) and nitric oxide (NO) were also elevated along with a reduction in glutathione reduced content (GSH), superoxide dismutase (SOD) and catalase (CAT) activity. Treatment with TPE considerably ameliorated the serum levels of liver enzymes, lowered MDA and NO levels, as well as elevated the antioxidant defense system. Also, TPE improved the histological structure and modulated apoptosis caused by nicotine. The current study proved the effectiveness of TPE as a natural antioxidant for the alleviation of nicotine-induced hepatic biochemical and histopathological alterations through attenuating oxidative stress, improving antioxidant systems and abrogating apoptosis.

Nigella sativa, active principle thymoquinone, alleviates palmitate-induced cytotoxicity, inflammation and bioenergetic disruptions in macrophages: An invitro study model

Thymoquinone (TQ) is one of the main phytochemical bioactive ingredients in Nigella sativa, with reported immunity-boosting properties. The current study evaluated the anti-inflammatory effect of TQ against inflammation brought on by free fatty acid Palmitate (PA) using macrophages raw 264.7 cell line. Data revealed that TQ significantly improved the viability of basal and PA stimulated Macrophages at concentrations of 50 and 100 μg/mL. Also, TQ significantly reduced nitric oxide and triglyceride levels in PA-stimulated macrophages at concentrations of 50 and 100 μg/mL. The pro-inflammatory cytokines studies revealed that PA significantly increased the release of the cytokines TNF-α, MHGB-1, IL-1β, and IL-6. TQ at concentrations 25, 50, and 100 μg/ml significantly decreases the release of the studied cytokines in PA-stimulated macrophages to variable extents with parallel inhibition to their corresponding gene expression. Bioenergetic assays showed that PA significantly decreased cellular ATP, mitochondrial complexes I and III activities and mitochondrial membrane potential with a subsequent significant increase in lactate production. At the same time, TQ can alleviate the effect of PA on macrophages' bioenergetics parameters to variable extent based on TQ concentration. To conclude, TQ could mitigate palmitate-induced inflammation and cytotoxicity in macrophages by improving macrophage viability and controlling cytokine release with improved PA-induced bioenergetics disruption.

Tumor Microenvironment-Activatable Phototheranostic: Leveraging Nitric Oxide and Weak Acidity as Dual Biomarkers for Ratiometric Fluorescence, Photoacoustic Imaging, and Photothermal Therapy.

Tumor microenvironment-responsive phototheranostic agents are highly sought after for their ability to improve diagnostic accuracy and treatment specificity. Here, we introduce a novel single-molecule probe, POZ-NO, which is activated by nitric oxide (NO) and weak acidity, enabling dual-mode imaging and photothermal therapy (PTT) of tumors. In acidic environments with elevated NO levels, POZ-NO exhibits a distinctive ratiometric fluorescence signal shift from the red to near-infrared, accompanied by a 700 nm photoacoustic signal. Additionally, POZ-NO demonstrated potent photothermal effects upon NO and acidity activation, achieving an impressive conversion efficiency of 74.3% under 735 nm laser irradiation. In vivo studies confirm POZ-NO's ability to accurately image tumors through ratiometric fluorescence and photoacoustic modes while selectively treating tumors with PTT.

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.

The Hepatoprotective Effect of Trigonelline in Diabetic Rat Through Insulin-related IRS1-GLUT2 Pathway: A Biochemical, Molecular, Histopathological, and Immunohistochemical Study

The Hepatoprotective Effect of Trigonelline in Diabetic Rat Through Insulin-related IRS1-GLUT2 Pathway: A Biochemical, Molecular, Histopathological, and Immunohistochemical Study

Effect of Lactiplantibacillus plantatum HFY11 on Colitis in Mice

This study aimed to examine the potential impact of the intervention of Lactiplantibacillus plantatum HFY11 (LP-HFY11) on colitis using in vivo animal trials. The impact of LP-HFY11 intervention on colitis was determined by measuring the levels of relevant indicators in the intestine, colon, and blood after oxazolone-induced colitis in BALB/c mice. The results of the trial show that LP-HFY11 improved the colon weight-to-length ratio, reduced the colitis-induced colon length shortening, and reduced colonic abstinence. Furthermore, it decreased the levels of myeloperoxidase, nitric oxide, and malondialdehyde activities while increasing the glutathione content in the colon tissue of colitis-affected animals. LP-HFY11 lowered the interleukin-10 (IL-10) level and increased the IL-2 level in the serum of colitis mice. LP-HFY11 also upregulated the expression of neuronal nitric oxide synthase, endothelial nitric oxide synthase, c-Kit, and stem cell factor (SCF), and downregulated the expression of IL-8, C-X-C chemokine receptor type 2 (CXCR2), and inducible nitric oxide synthase (iNOS) in the colon tissue of mice with colitis. LP-HFY11 decreased the expression of Firmicutes in the gut while increasing the expression of Bacteroidetes, Bifidobacteria, and Lactobacillus. This indicates that LP-HFY11 could control physiological alterations in the serum and colon tissue, as well as the expression of gut microorganism.

Cough Response to High-Dose Inhaled Corticosteroids in Patients with Chronic Cough and Fractional Exhaled Nitric Oxide Levels ≥ 25ppb: A Prospective Study.

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.

Fatty acids in Plantago asiatica seeds are responsible for the production of the pro-inflammatory mediator nitric oxide

Background: Plantago asiatica L. (Plantaginaceae) commonly grows in East Asia, with its seeds (Shazenshi), having been used as diuretic and anti-inflammatory drugs in traditional Japanese medicine. It is not known which constituents of P. asiatica seeds elicit the anti-inflammatory effects, such as reduced expression of the inducible nitric oxide synthase (iNOS) in interleukin (IL)-1β-treated hepatocytes which leads to a reduction in the pro-inflammatory mediator nitric oxide (NO). Objective: To identify the anti-inflammatory constituents of P. asiatica seeds, the anti-inflammatory activity of purified constituents was determined by assaying NO production in IL-1β-treated hepatocytes. Methods: P. asiatica seeds were extracted with 50% methanol and successively fractionated into three crude fractions with ethyl acetate (EtOAc) and n-butanol. The compounds were methylated and analyzed by gas chromatography–mass spectrometry (GC–MS). Primary cultured rat hepatocytes were prepared by collagenase perfusion, and P. asiatica seed extract (PASE), a fraction, or a compound was added to the culture medium with IL-1β and incubated at 37 °C. Potency of each fraction was determined by the Griess method for measuring the levels of nitrite in the medium. Results: PASE suppressed IL-1β-induced NO production without showing cytotoxicity, and an EtOAc-soluble fraction of PASE significantly inhibited NO production. GC–MS analysis detected 26 distinct fatty acids as their methyl esters in this fraction. Among them, three unsaturated fatty acids (linoleic, oleic, and α-linolenic acids) and palmitic acid were abundant. These unsaturated fatty acids are known to reduce NO levels. In contrast, acteoside and aucubin, which are thought to be present in the n-butanol-soluble fraction, showed only a low level of NO production suppression. Conclusion: The EtOAc-soluble fraction of PASE included many fatty acids, which may suppress the production of NO. The results imply that the anti-inflammatory activity of P. asiatica seeds may be produced by three unsaturated fatty acids. Because the fatty acids are abundant in the seeds of medicinal plants, they are likely to contribute to anti-inflammatory activity of the seeds. Keywords: Plantain seed, polyunsaturated fatty acid, Kampo medicine, hepatocyte, nitric oxide.

Effect on the splenocyte function of weaned piglets induced by continuous lipopolysaccharide injections

Abstract Introduction When piglets are exposed to pathogens for a long period, the immune system organs, among them the spleen, play a major role in combating the stress caused by those pathogens. In the present study, the effect on splenocyte function was investigated in a model of weaned piglets in which stress was induced by multiple low doses of lipopolysaccharide (LPS). Material and Methods Forty-eight 28-day-old piglets were divided into two groups: the LPS group and the control group. During the experimental period of thirteen days, the LPS group was intraperitoneally injected with LPS (100 μg/kg) once per day, and the control group was injected with the same volume of 0.9% sterile saline. On the 1st, 5th, 9th and 13th days, the piglets’ spleens were collected for isolating splenocytes. The proliferation ability of splenocytes was evaluated by the cell-counting-kit 8 method. Flow cytometry was used to detect cell cycle stage and apoptosis, and the nitric oxide level of cell supernatant was also tested. Results In the experimental group, the proliferation ability of splenocytes was enhanced, the proportion of cells in the G0/G1 phase was smaller, and cells were promoted to the S and G2/M phases. Meanwhile, apoptosis was suppressed and nitric oxide release upregulated. The results were significantly different between the LPS group and the control group on the 5th and 9th days. Conclusion The difference between the results of one group and those of the other suggest that after the 5th LPS injection, multiple low doses of LPS activated splenocytes and restored the number of splenocytes, which maintained and possibly enhanced the regulation of the immune function of the spleen.

Regulation of Oxidative Stress and Apoptosis in Streptozotocin-Induced Diabetic Rats by Egyptian Sidr Honey.

Diabetesmellitusis a global health issuecharacterized by hyperglycemia which leads over time to severe damage to numerous tissues.The present study aimed to estimate the effect of Egyptian Sidr honey against streptozotocin-induced diabetes in rats. Diabetic rats were treated with Sidr honey daily for 4 consecutive weeks. The biochemical profile of blood samples was measured. Furthermore, the activity of antioxidant enzymes, nitric oxide (NO), and malonaldehyde (MDA) were examined in liver and pancreas tissues. Moreover, the expression of Bax, Caspase-3, and Bcl2 proteins were measured. Results revealed that the capability of Sidr honey to decline the elevated blood glucose and fructosamine levels compared to diabetic rats. Also, the honey decreased the levels of NO and MDA. Furthermore, it regulated the antioxidant enzymes activity. Moreover, it reduced the expression levels of Caspase-3 and Bax while increased the Bcl2 level. In conclusion, Sidr honey can regulate hyperglycemia, oxidative stress, apoptosis, and antioxidant enzymes in STZ-induced diabetic rats.

Effects of Euphorbia characias subsp. characias flower extracts on nociceptive pain and acute inflammatory models in mice

Pain and inflammation are major health issues worldwide, leading to negative consequences. Despite several drugs being available to manage these conditions, their effectiveness can be limited by cost, adverse reactions, and potential tolerance and dependence with long-term use. Euphorbia characias traditionally used in folk medicine for its diverse biological activities - including antiproliferative, antimicrobial, and anti-inflammatory effects - has not been extensively studied in vivo for its analgesic and anti-inflammatory properties. In this study, the antinociceptive and anti-inflammatory properties of the water and ethanolic extracts of E. characias flowers (ECAEFl and ECEEFl) were evaluated using various models. Both extracts significantly reduced paw licking time in a formalin-induced paw licking model, with ECAEFl specifically targeting and ECEEFl affecting both the neurogenic and inflammatory phases. Additionally, in the carrageenan-induced cell migration model, both extracts showed a significant decrease in leukocyte migration, protein extravasation and nitric oxide levels, further demostrating their anti-inflammatory activity. High-Resolution HPLC-ESI-QTOF-MS-MS and HPLC-PDA analysis characterized the chemical composition of the extracts, identifying a significant presence of phenolic compounds, particularly quercetin and its derivatives, which likely contribute to the observed biological activities. These findings highlight the potential of E. characias extracts as natural sources of compounds with antinociceptive and anti-inflammatory properties. Further investigations are needed to elucidate the underlying mechanisms and explore their therapeutic potential in pain and inflammation-related disorders.

Real-time and specific monitoring of nitric oxide and evaluating of the oxidative stress in living cells and zebrafish under the pollutant exposure using a carbon dot-based composite fluorescent probe

Nitric oxide (NO) functions as an essential signalling molecule in various physiological and pathological pathways. In vitro and vivo redox processes mediated by reactive oxygen species (ROS) and nitric oxide (NO) directly influence the intracellular state. In this study, a red-emitting fluorescent nanoprobe, N,S-CDs@Zn-ICA, was synthesized to monitor NO fluctuations in living cells and zebrafish under the exposure to various pollutants. Red-emissive carbon dots (N,S-CDs) were synthesized by a hydrothermal method using o-phenylenediamine and urea as carbon / nitrogen sources, and H2SO4 as sulfur source. Glutathione (GSH) was introduced to link N,S-CDs with metal organic complexes (Zn-ICA) through an amidation reaction to fabricate a carbon dot-based composite fluorescent probe, which greatly improved the selectivity, stability, and response time of the N,S-CDs. The composite probe has high selectivity and sensitivity with limit of detection (LOD) of 96.0 nM. Furthermore, the proposed probe was successfully used to monitor the dynamic changes in NO levels and evaluate oxidative stress in MCF-7 cells and zebrafish under the exposure to various pollutants, including seven heavy metal ions (such as Pb2+, Cd2+, and Hg2+) and nine organic pollutants at different concentrations and exposure times. This work provides a novel strategy for constructing highly selective and red-emitting fluorescent probe for real-time and dynamic monitoring of NO and further evaluating oxidative stress induced by pollutants in vitro and in vivo via fluorescence imaging.

Impact of Inducible Nitric Oxide Synthase Activation on Endothelial Behavior under Magnesium Deficiency

Endothelial dysfunction is a crucial event in the early pathogenesis of cardiovascular diseases and is linked to magnesium (Mg) deficiency. Indeed, in endothelial cells, low Mg levels promote the acquisition of a pro-inflammatory and pro-atherogenic phenotype. This paper investigates the mechanisms by which Mg deficiency promotes oxidative stress and affects endothelial behavior in human umbilical vascular endothelial cells (HUVECs). Our data show that low Mg levels trigger oxidative stress initially by increasing NAPDH oxidase activity and then by upregulating the pro-oxidant thioredoxin-interacting protein TXNIP. The overproduction of reactive oxygen species (ROS) activates NF-κB, leading to its increased binding to the inducible nitric oxide synthase (iNOS) promoter, with the consequent increase in iNOS expression. The increased levels of nitric oxide (NO) generated by upregulated iNOS contribute to disrupting endothelial cell function by inhibiting growth and increasing permeability. In conclusion, we provide evidence that multiple mechanisms contribute to generate a pro-oxidant state under low-Mg conditions, ultimately affecting endothelial physiology. These data add support to the notion that adequate Mg levels play a significant role in preserving cardiovascular health and may suggest new approaches to prevent or manage cardiovascular diseases.

Exercise interventions for the effect of endothelial function in hypertensive patients: A systematic review and meta-analysis.

Endothelial dysfunction is crucial factor to the hypertension occurrence, and controversy remains regarding the effect of exercise on improving endothelial function in hypertensive patients. The authors used meta-analysis to evaluate the intervention effect of exercise on endothelial function in hypertensive patients and to investigate exercise protocols that may have a greater intervention effect. A total of 37 studies and a total of 2801 participants were included. The results were as follows: endogenous nitric oxide (NO)[SMD=.89, 95% CI (.48, 1.30), p<.0001], endothelin-1 (ET-1): [SMD=-.94, 95% CI (-1.15, -.73), p<.0001], flow-mediated dilation (FMD) [SMD=-.57, 95% CI (.36,.79), p<.000001]. In subgroup analysis, high-intensity aerobic exercise, with a single exercise duration of 35-50min, 3-4 times/week for a total of 10-12weeks, had the largest amount of intervention effect on NO, and moderate-intensity resistance exercise, with a single exercise duration of ≥60min, 6 times/week for a total of 15-18weeks, had the largest amount of intervention effect on ET-1. In conclusion, exercise can improve NO levels, FDM levels, and reduce ET-1 secretion of hypertension patients, thereby improve their endothelial function. The ideal intervention effect of improving NO level was more likely to be obtained by taking the exercise prescription of high-intensity aerobic exercise with a single exercise duration of 35-50min, 3-4 times/week for 10-12weeks; the ideal intervention effect of improving ET-1 was more likely to be obtained by taking the exercise prescription of oderate -intensity resistance exercise with a single exercise duration of ≥60min, 6 times/week for 15-18weeks.