Evidence to support cultivated fruiting body of Ophiocordyceps sinensis (Ascomycota)'s role in relaxing airway smooth muscle.

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiocordyceps sinensis (O. sinensis) is a genus of Ascomycete fungus that is endemic to the alpine meadows of the Tibetan Plateau and adjoining Himalayas. It has been used traditionally as a tonic to improve respiratory health in ancient China as well as to promote vitality and longevity. Bioactive components found in O. sinensis such as adenosine, cordycepin, 3-deoxyadenosine, L-arginine and polysaccharides have gained increasing interest in recent years due to their antioxidative and other properties, which include anti-asthmatic, antiviral, immunomodulation and improvement of general health. AIM OF THE STUDY: This study's primary aim was to investigate the effect of a cultivated fruiting body of O. sinensis strain (OCS02®) on airways patency and the secondary focus was to investigate its effect on the lifespan of Caenorhabditis elegans. MATERIALS AND METHODS: A cultivated strain, OCS02®, was employed and the metabolic profile of its cold-water extract (CWE) was analysed through liquid chromatography-mass spectrometry (LC-MS). Organ bath approach was used to investigate the pharmacological properties of OCS02® CWE when applied on airway tissues obtained from adult male Sprague-Dawley rats. The airway relaxation mechanisms of OCS02® CWE were explored using pharmacological tools, where the key regulators in airway relaxation and constriction were investigated. For the longevity study, age-synchronised, pos-1 RNAi-treated wild-type type Caenorhabditis elegans at the L4 stage were utilised for a lifespan assay. RESULTS: Various glycopeptides and amino acids, particularly a high concentration of L-arginine, were identified from the LC-MS analysis. In airway tissues, OCS02® CWE induced a significantly greater concentration-dependent relaxation when compared to salbutamol. The relaxation response was significantly attenuated in the presence of NG-Nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) and several K+ channel blockers. The longevity effect induced by OCS02® CWE (5 mg/mL and above) was observed in C. elegans by at least 17%. CONCLUSIONS: These findings suggest that the airway relaxation mechanisms of OCS02® CWE involved cGMP-dependent and cGMP-independent nitric oxide signalling pathways. This study provides evidence that the cultivated strain of OCS02® exhibits airway relaxation effects which supports the traditional use of its wild O. sinensis in strengthening respiratory health.

Tumor microenvironment-modulated nanoparticles with cascade energy transfer as internal light sources for photodynamic therapy of deep-seated tumors.

Photodynamic therapy (PDT) is an appealing modality for cancer treatments. However, the limited tissue penetration depth of external-excitation light makes PDT impossible in treating deep-seated tumors. Meanwhile, tumor hypoxia and intracellular reductive microenvironment restrain the generation of reactive oxygen species (ROS). To overcome these limitations, a tumor-targeted self-illuminating supramolecular nanoparticle T-NPCe6-L-N is proposed by integrating photosensitizer Ce6 with luminol and nitric oxide (NO) for chemiluminescence resonance energy transfer (CRET)-activated PDT. The high H2O2 level in tumor can trigger chemiluminescence of luminol to realize CRET-activated PDT without exposure of external light. Meanwhile, the released NO significantly relieves tumor hypoxia via vascular normalization and reduces intracellular reductive GSH level, further enhancing ROS abundance. Importantly, due to the different ROS levels between cancer cells and normal cells, T-NPCe6-L-N can selectively trigger PDT in cancer cells while sparing normal cells, which ensured low side effect. The combination of CRET-based photosensitizer-activation and tumor microenvironment modulation overcomes the innate challenges of conventional PDT, demonstrating efficient inhibition of orthotopic and metastatic tumors on mice. It also provoked potent immunogenic cell death to ensure long-term suppression effects. The proof-of-concept research proved as a new strategy to solve the dilemma of PDT in treatment of deep-seated tumors.

Stallion Sperm Freezing with Different Extenders: Role of Antioxidant Activity and Nitric Oxide Production.

Sensitivity to freezing remains a critical issue in stallion semen cryopreservation procedures. To explore this topic in-depth, semen was collected from ten stallions, diluted with three different extenders, transported to the laboratory, and then centrifuged and frozen with four different extenders. We conducted analyses of sperm kinetics, mitochondrial membrane potential (MMP), and hydrogen peroxide content both before and after freezing. Additionally, we assessed antioxidant activity using the ABTS and FRAP methods and measured nitric oxide stable metabolites (NOx) in the blank extenders, seminal plasma, and extenders conditioned by spermatozoa before and after freezing. We found significant variability in the antioxidant activity and NOx content of the blank extenders and the seminal plasma. In the seminal plasma, ABTS-based antioxidant activity and NOx values were correlated with some sperm kinematic parameters and MMP in refrigerated semen, while no correlation was observed in frozen sperm parameters. Sperm function varied significantly between stallions but not between extenders, either before or after freezing. However, significant differences in antioxidant activities and NOx values were found among extenders conditioned following freezing. These results provide new insights into the factors contributing to the variability in individual stallions' tolerance to sperm freezing.

No Difference between the Efficacy of High-Nitrate and Low-Nitrate Vegetable Supplementation on Blood Pressure after 16 Weeks in Individuals with Early-Stage Hypertension: An Exploratory, Double-Blinded, Randomized, Controlled Trial.

Dietary inorganic nitrate lowers blood pressure (BP) in healthy individuals through improved nitric oxide (NO) bioavailability. However, there is limited evidence examining the long-term effects of dietary nitrate for managing hypertension. We aimed to determine whether the sustained intake of dietary nitrate improved BP and cardiovascular disease (CVD) risk factors in individuals with early-stage hypertension. The Dietary Nitrate (NO3) on BP and CVD Risk Factors (DINO3) Trial was a multi-center, double-blinded, parallel, randomized, controlled trial in participants with elevated BP. Participants were supplemented with high-nitrate (HN) (~400 mg nitrate) or low-nitrate (LN) vegetable powder (~50 mg nitrate) on top of their usual diets for 16 weeks. The primary outcome was office systolic BP at 16 weeks. The secondary outcomes were 24 h ambulatory BP, central BP, heart-rate-corrected augmentation index (AIx75), carotid-femoral pulse wave velocity (cf-PWV), lipids, and high-sensitivity C-reactive protein (hs-CRP). Sixty-six participants were randomized at baseline (39M:27F, age: 51.5 ± 10.8 years, BMI:27.9 ± 3.2 kg/m2). In an intention-to-treat analysis, no differences were observed between HN and LN groups in terms of office systolic BP at 16 weeks (3.91 ± 3.52 mmHg, p = 0.27) or secondary outcomes. In this exploratory study, sustained HN vegetable supplementation did not exhibit more favorable vascular effects than LN vegetable supplementation in individuals with elevated BP.

Sex differences in the predictors of skeletal muscle microvascular reactivity in older individuals.

Aging is associated with an increased risk of cardiovascular disease and vascular dysfunction. Reduced nitric oxide bioavailability is considered one of the key mechanisms underlying vascular dysfunction in large arteries of older adults. However, the relationship between cardiovascular disease risk factors, nitric oxide bioavailability, and skeletal muscle microvascular reactivity, an early hallmark in cardiovascular disease progression, is unclear in older individuals. Also uncertain is whether this relationship is influenced by sex. Therefore, this study assessed the association between cardiovascular disease risk factors, circulating markers of nitric oxide availability (plasma nitrate and nitrite), and skeletal muscle microvascular reactivity in older individuals. First, we confirmed in a cohort of young and older individuals that aging is associated with skeletal muscle microvascular dysfunction. Next, we observed that skeletal muscle microvascular reactivity (P = 0.653; η2 = 0.016) and circulating nitric oxide metabolites (Nitrate: P = 0.641, η2 = 0.011; Nitrite: P = 0.560, η2 = 0.017; NOx: P = 0.639, η2 = 0.011) did not differ between older males and females. Finally, using multivariate regression models, we found that: (i) the number of cardiovascular risk factors was negatively associated with skeletal muscle microvascular reactivity in older males and females (B = -0.132, P = 0.044); (ii) the relationship between plasma nitrite and skeletal muscle microvascular reactivity was influenced by sex (F = 6.837, P = 0.016); and (iii) skeletal muscle microvascular reactivity in older females displayed a strong positive association with plasma nitrite (R2 = 0.720, P < 0.001). While the impact of cardiovascular disease risk factors on skeletal muscle microvascular reactivity was not influenced by sex, sex-related discrepancies were found in the relationship between nitric oxide bioavailability and skeletal muscle microvascular reactivity in older individuals.

Brucella induced upregulation of NO promote macrophages glycolysis through the NF-κB/G6PD pathway.

Increased glycolytic metabolism recently emerged as an essential process driving host defense against Brucella, but little is known about how this process is regulated during infection. We have identified a critical role for nuclear factor kappa B (NF-κB) transcription factor regulation in glycolytic switching during Brucella infection for the first time. Chromatin immunoprecipitation with next-generation sequencing for NF-κB and DNA Pull-Down revealed two novel NF-κB-binding sites in the enhancer region of the Nitric oxide (NO)production-response regulator gene glucose-6-phosphate dehydrogenase (G6PD), which is important for the switch to glycolysis during a Brucella infection. These findings demonstrate that Brucella drives metabolic reprogramming by inhibiting host oxidative phosphorylation (OXPHOS) and enhancing its glycolysis via the NF-κB-G6PD-NO-pathway. These studies provide a theoretical basis for investigating drugs or vaccines to control Brucella colonization and induction of undulant by manipulating host metabolic patterns.

Predicting dupilumab effectiveness with Type-2 biomarkers: A real-world study of severe asthma.

BACKGROUND: The therapeutic effectiveness of dupilumab for severe asthma in real-world settings is yet to be prospectively investigated across multiple institutions, and uncertainties persist regarding predictive factors for its effectiveness. We aimed to assess the effectiveness of dupilumab and identify predictors of its effectiveness in real-world settings using two type-2 biomarkers: FeNO concentration and blood eosinophil count. METHODS: This prospective multicenter study included 103 patients with severe asthma. Exacerbations and respiratory functions were monitored for 24 weeks. Asthma control was evaluated using the Asthma Control Questionnaire-5. Clinical symptoms and their impact on cough and sputum were assessed using the Cough and Sputum Assessment Questionnaire (CASA-Q). Subgroup analyses of type-2 biomarkers were conducted based on FeNO levels and blood eosinophil counts at baseline. RESULTS: Treatment with dupilumab led to a reduction in exacerbations and enhancement in asthma control, FEV1, and CASA-Q scores. FEV1 improvement was correlated with enhancement in the sputum domain of the CASA-Q. Patients exhibiting elevated FeNO levels and blood eosinophil counts demonstrated more significant enhancements in FEV1. CASA-Q sputum domain scores were significantly higher in the group with elevated eosinophil counts. Regression analysis revealed that FeNO levels and blood eosinophil counts are significant predictors of FEV1 improvement, with blood eosinophil counts also predicting sputum improvement in patients treated with dupilumab. CONCLUSIONS: Type-2 biomarkers may act as indicators of improvement in FEV1 and sputum outcomes among patients with severe asthma undergoing dupilumab treatment in real-world settings.

Inhibitors of NLRP3 Inflammasome Formation: A Cardioprotective Role for the Gasotransmitters Carbon Monoxide, Nitric Oxide, and Hydrogen Sulphide in Acute Myocardial Infarction.

Myocardial ischaemia reperfusion injury (IRI) occurring from acute coronary artery disease or cardiac surgical interventions such as bypass surgery can result in myocardial dysfunction, presenting as, myocardial "stunning", arrhythmias, infarction, and adverse cardiac remodelling, and may lead to both a systemic and a localised inflammatory response. This localised cardiac inflammatory response is regulated through the nucleotide-binding oligomerisation domain (NACHT), leucine-rich repeat (LRR)-containing protein family pyrin domain (PYD)-3 (NLRP3) inflammasome, a multimeric structure whose components are present within both cardiomyocytes and in cardiac fibroblasts. The NLRP3 inflammasome is activated via numerous danger signals produced by IRI and is central to the resultant innate immune response. Inhibition of this inherent inflammatory response has been shown to protect the myocardium and stop the occurrence of the systemic inflammatory response syndrome following the re-establishment of cardiac circulation. Therapies to prevent NLRP3 inflammasome formation in the clinic are currently lacking, and therefore, new pharmacotherapies are required. This review will highlight the role of the NLRP3 inflammasome within the myocardium during IRI and will examine the therapeutic value of inflammasome inhibition with particular attention to carbon monoxide, nitric oxide, and hydrogen sulphide as potential pharmacological inhibitors of NLRP3 inflammasome activation.

Role of Nitric Oxide Synthases in Respiratory Health and Disease: Insights from Triple Nitric Oxide Synthases Knockout Mice.

The system of nitric oxide synthases (NOSs) is comprised of three isoforms: nNOS, iNOS, and eNOS. The roles of NOSs in respiratory diseases in vivo have been studied by using inhibitors of NOSs and NOS-knockout mice. Their exact roles remain uncertain, however, because of the non-specificity of inhibitors of NOSs and compensatory up-regulation of other NOSs in NOS-KO mice. We addressed this point in our triple-n/i/eNOSs-KO mice. Triple-n/i/eNOSs-KO mice spontaneously developed pulmonary emphysema and displayed exacerbation of bleomycin-induced pulmonary fibrosis as compared with wild-type (WT) mice. Triple-n/i/eNOSs-KO mice exhibited worsening of hypoxic pulmonary hypertension (PH), which was reversed by treatment with sodium nitrate, and WT mice that underwent triple-n/i/eNOSs-KO bone marrow transplantation (BMT) also showed aggravation of hypoxic PH compared with those that underwent WT BMT. Conversely, ovalbumin-evoked asthma was milder in triple-n/i/eNOSs-KO than WT mice. These results suggest that the roles of NOSs are different in different pathologic states, even in the same respiratory diseases, indicating the diversity of the roles of NOSs. In this review, we describe these previous studies and discuss the roles of NOSs in respiratory health and disease. We also explain the current state of development of inorganic nitrate as a new drug for respiratory diseases.

Potential of Coffee Cherry Pulp Extract against Polycyclic Aromatic Hydrocarbons in Air Pollution Induced Inflammation and Oxidative Stress for Topical Applications.

Airborne particulate matter (PM) contains polycyclic aromatic hydrocarbons (PAHs) as primary toxic components, causing oxidative damage and being associated with various inflammatory skin pathologies such as premature aging, atopic dermatitis, and psoriasis. Coffee cherry pulp (CCS) extract, rich in chlorogenic acid, caffeine, and theophylline, has demonstrated strong antioxidant properties. However, its specific anti-inflammatory effects and ability to protect macrophages against PAH-induced inflammation remain unexplored. Thus, this study aimed to evaluate the anti-inflammatory properties of CCS extract on RAW 264.7 macrophage cells exposed to atmospheric PAHs, compared to chlorogenic acid (CGA), caffeine (CAF), and theophylline (THP) standards. The CCS extract was assessed for its impact on the production of nitric oxide (NO) and expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Results showed that CCS extract exhibited significant antioxidant activities and effectively inhibited protease and lipoxygenase (LOX) activities. The PAH induced the increase in intracellular reactive oxygen species, NO, TNF-α, IL-6, iNOS, and COX-2, which were markedly suppressed by CCS extract in a dose-dependent manner, comparable to the effects of chlorogenic acid, caffeine, and theophylline. In conclusion, CCS extract inhibits PAH-induced inflammation by reducing pro-inflammatory cytokines and reactive oxygen species (ROS) production in RAW 264.7 cells. This effect is likely due to the synergistic effects of its bioactive compounds. Chlorogenic acid showed strong antioxidant and anti-inflammatory activities, while caffeine and theophylline enhanced anti-inflammatory activity. CCS extract did not irritate the hen's egg chorioallantoic membrane. Therefore, CCS extract shows its potential as a promising cosmeceutical ingredient for safely alleviating inflammatory skin diseases caused by air pollution.

Liposome preparation of alpha-arbutin: stability and toxicity assessment using mouse B16F10 melanoma cells.

Melanoma is the most aggressive type of skin cancer, with few therapeutic alternatives following metastasis development. In recent years, drug delivery-associated nanotechnology has shown promising targeted results with diminished adverse effects compared to conventional treatments. This study aimed to (1) examine the effects of plant-derived α-arbutin, a natural compound and (2) compare these findings with bioactively developed liposomes containing α-arbutin utilizing the B16-F10 murine melanoma cell line as a model. Liposomes were obtained through reversed-phase evaporation by applying a spray dryer to assess their stability. The following biologic assays were measured cytotoxicity/antiproliferative (MTT, Neutral Red, and dsDNA PicoGreen). In addition, the levels of melanin and purinergic enzymes were also measured. The production of reactive oxygen species (ROS) and nitric oxide (NO) was determined as a measure of oxidative state. Treatment with nano-liposome containing alpha-arbutin induced a significant 68.4% cytotoxicity, similar to the positive control, in the B16-F10 murine melanoma cell line at 72 hr. Further, arbutin and liposomes containing alpha-arbutin increased levels of ROS and nitrite formation at 72 hr at the highest concentration (100 and 300 µg/ml) of treatments. Arbutin and liposomes containing alpha-arbutin reduced melanin levels at all tested concentrations. In addition, arbutin and alpha-arbutin containing liposomes lowered nucleotides (AMP, ADP, and ATP) and nucleoside (adenosine) levels in melanoma cells. Evidence suggests that α-arbutin containing liposome can be considered as an alternative immunosuppressive agent stimulated in melanoma treatment.

Methemoglobin in critically ill septic patients.

Aim: Higher nitric oxide (NO) levels correlate with adverse sepsis outcomes but are challenging to measure. Methemoglobin (MetHb), a measurable product of NO, has not been utilized for risk stratification.Methodology: All patients with sepsis admitted to the intensive care unit (ICU) that had at least one MetHb measurement within 24 h of ICU admission were retrospectively analyzed. We assessed the epidemiology and associations of MetHb with hospital mortality.Results: Among 7724 patients, 1046 qualified. Those with MetHb ≥1.6% showed significantly higher mortality and fewer days alive outside the hospital by day 28. MetHb levels ≥1.6% independently predicted increased 28-day mortality.Conclusion: Our findings suggest MetHb, easily obtainable from arterial blood gases, can significantly enhance sepsis risk stratification.

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Soy lysolecithin prevents hypertension and cognitive impairment induced in mice by high salt intake by inhibiting intestinal inflammation.

High salt (HS) intake induces hypertension and cognitive impairment. Preventive strategies include against dietary supplements. Soybean lecithin is a widely used phospholipid supplement. Lysolecithin is important in cell signaling, digestion, and absorption. This study aimed to investigate the effects of lysophosphatidylcholine containing >70% of the total phospholipids (LPC70), on hypertension and cognitive impairment induced in mice by HS intake. Mice were provided with HS solution (2% NaCl in drinking water) with or without LPC70 for 12 weeks. Blood pressure, cognitive function, and inflammatory response of intestine were determined. Hypertension and impaired object recognition memory induced by HS intake were implicated with increased inducible nitric oxide synthase in the small intestine and tau hyperphosphorylation in the prefrontal cortex. LPC70 treatment prevented cognitive impairment by suppressing inducible nitric oxide synthase and tau hyperphosphorylation. LPC70 may be valuable as a functional food component in preventing HS-induced cognitive impairment.

Exogenous nitric oxide treatment delays the senescence of postharvest mung bean sprouts by regulating ascorbic acid metabolism.

BACKGROUND: This study evaluated the effects of nitric oxide (NO) treatment on ascorbic acid (AsA) metabolism and mung bean sprout quality. It examined changes in the AsA content, enzyme activity associated with AsA metabolism, antioxidant capacity, cell membrane composition, and cellular structure to clarify the effects of NO on mung bean sprouts. RESULTS: Nitric oxide treatment preserved mung bean sprout quality by enhancing significantly the activity of enzymes involved in the l-galactose pathway (including guanosine diphosphate (GDP)glutathione (-d-mannose pyrophosphorylase, GDP-mannose-3',5'-epimerase, GDP-l-galactose phosphorylase, l-galactose-1-phosphate phosphatase, l-galactose dehydrogenase, and l-galactose-1,4-lactone dehydrogenase) and the AsA-glutathione (GSH)(Beijing Solarbio Science and Technology Co.,Ltd., Beijing, China) cycle (including ascorbate peroxidase, ascorbic acid oxidase, glutathione reductase, dehydroascorbate reductase, and monodehydroascorbate reductase) during the germination and storage stage. Increased enzyme activity led to an increase in AsA content and enhanced antioxidant capacity, and reduced the membrane lipid damage in mung bean sprouts. This was demonstrated by higher levels of DPPH radical scavenging capacity, unsaturated fatty acids and phospholipids, along with lower levels of hydrogen peroxide, superoxide anions, and malondiadehyde, in NO-treated mung bean sprouts. Scanning electron microscopy also revealed that NO treatment maintained the integrity of the cellular structure of the mung bean sprouts. CONCLUSION: Nitric oxide accelerates AsA metabolism effectively by regulating the biosynthesis and regeneration of AsA in mung bean sprouts. These changes increased AsA levels, alleviated membrane lipid damage, delayed senescence, and maintained the quality of mung bean sprouts during storage. © 2024 Society of Chemical Industry.

Graph-based, dynamics-preserving reduction of (bio)chemical systems.

Complex dynamical systems are often governed by equations containing many unknown parameters whose precise values may or may not be important for the system's dynamics. In particular, for chemical and biochemical systems, there may be some reactions or subsystems that are inessential to understanding the bifurcation structure and consequent behavior of a model, such as oscillations, multistationarity and patterning. Due to the size, complexity and parametric uncertainties of many (bio)chemical models, a dynamics-preserving reduction scheme that is able to isolate the necessary contributors to particular dynamical behaviors would be useful. In this contribution, we describe model reduction methods for mass-action (bio)chemical models based on the preservation of instability-generating subnetworks known as critical fragments. These methods focus on structural conditions for instabilities and so are parameter-independent. We apply these results to an existing model for the control of the synthesis of the NO-detoxifying enzyme Hmp in Escherichia coli that displays bistability.

Beneficial Effects of Cocoa Flavanols on Microvascular Responses in Young Men May Be Dependent on Ethnicity and Lifestyle.

Cocoa flavan-3-ols affect endothelium-dependent responses in resistance vessels and microcirculation has received little attention. We tested the effects of dark chocolate consumption (396 mg total flavanols/day for 3 days) in two Groups of 10 men (18-25 years; non-smokers) each comprising equal numbers of White European (WE) and South Asian (SA) ethnicity. In Group 1, dark chocolate did not affect reactive hyperaemia in forearm muscle, but augmented muscle dilatation evoked by acute mental stress, and reactive hyperaemia and acetylcholine (ACh)-evoked dilatation in cutaneous microcirculation. Conversely, in Group 2, chocolate did not affect cutaneous reactive hyperaemia or ACh-evoked dilatation, but these responses were blunted in Group 1 relative to Group 2. Further, when Groups 1 and 2 were combined, responses were blunted in SAs relative to WEs, augmented by chocolate in SAs only. In Group 2 individuals whose ACh-evoked dilatation was attenuated by nitric oxide synthase (NOS) inhibition, ACh-evoked dilatation was not altered after chocolate, but the attenuating effect of NOS inhibition was lost. Conversely, in Group 2 individuals whose ACh-evoked dilatation was enhanced by NOS inhibition, ACh-evoked dilatation was also augmented by chocolate. We propose that in resistance and microvessels of young men, cocoa flavan-3-ols preferentially augment endothelium-dependent dilator responses whose responses are depressed by familial and lifestyle factors more prevalent in SAs than Wes. Flavan-3-ols may facilitate the NOS pathway but also influence other endothelium-dependent dilators.

Prognostic value of serum total IgE and FeNO levels in children with atopic constitution bronchiolitis.

Bronchiolitis is a significant factor contributing to bronchial asthma in infants and young children. After treatment, recurrent wheezing symptoms often occur, especially in children with atopic constitution, who tend to have more severe conditions and poorer prognosis. Therefore, exploring the prognostic value of total serum immunoglobulin E (tIgE) and fractional exhaled nitric oxide (FeNO) levels in children with atopic constitution who suffer from bronchiolitis is of great significance. A total of 260 children with bronchiolitis admitted to our hospital from October 2020 to June 2022 were regarded as the research subjects with prospective study, according to whether the children had atopic constitution, they were grouped into non atopic constitution group (n = 156) and atopic constitution group (n = 104); after 6 months of treatment, children with atopic constitution were grouped into a good prognosis group (n = 58) and a poor prognosis group (n = 46) based on their prognosis; in addition, 260 healthy children who underwent physical examination and had clinical data consistent with those of children with bronchiolitis were regarded as the reference group. The serum tIgE and FeNO levels of each group were compared; multivariate Logistic regression was applied to analyze the prognostic factors of children with atopic constitution bronchiolitis; ROC curve was applied to analyze the predictive value of tIgE and FeNO levels after treatment for the prognosis of children with atopic constitution bronchiolitis. The tIgE levels in the control group, non-atopic group, and atopic group [(123.54 ± 29.62) IU/mL, (245.71 ± 30.59) IU/mL, (316.46 ± 31.78) IU/mL, respectively] increased sequentially, with statistically significant differences (F = 1766.954, P = 0.000). The FeNO levels in the control group, non-atopic group, and atopic group [(8.36 ± 3.57) ppb, (15.28 ± 3.69) ppb, (19.84 ± 3.58) ppb, respectively] also increased sequentially, with statistically significant differences (F = 765.622, P = 0.000). The tIgE, FeNO, proportion of patients with asthma family history, and proportion of patients with allergic family history in the poor prognosis group were obviously higher than those in the good prognosis group (P < 0.05). Multivariate Logistic regression analysis showed that family history of asthma, family history of allergies, tIgE, and FeNO were influencing factors for the prognosis of children with atopic bronchiolitis (P < 0.05). The AUC of the combination of tIgE and FeNO in predicting the prognosis of children with atopic constitutional bronchiolitis was 0.910, with a sensitivity of 78.26% and a specificity of 93.10%, which was superior to the independent prediction of tIgE and FeNO (Zcombined detection-tIgE = 2.442, Zcombined detection-FeNO = 3.080, P = 0.015, 0.002). The levels of tIgE and FeNO in children with atopic constitution bronchiolitis are obviously increased, and the combination of the two has high predictive value for the prognosis of atopic constitution bronchiolitis.

Current clinical framework on nitric oxide role in periodontal disease and blood pressure.

OBJECTIVES: In this review, we explored potential associations between NO and its derivatives, nitrite and nitrate, with periodontal and cardiovascular diseases, with special emphasis on the former. By providing a state-of-the-art and integrative understanding of this topic, we aimed to shed light on the potential role of these three nitrogen oxides in the periodontitis-hypertension nexus, identify knowledge gaps, and point out critical aspects of the experimental methodologies. MATERIALS AND METHODS: A comprehensive literature review was conducted on human salivary and plasma concentrations of nitrate and nitrite, and their impact on periodontal and cardiovascular health. RESULTS: A nitrate-rich diet increases nitrate and nitrite levels in saliva and plasma, promoting oral health by favorably altering the oral microbiome. Chlorhexidine (CHX) mouthrinses disrupt the nitrate-nitrite-NO pathway, reducing NO bioavailability, and potentially affecting blood pressure. This is because CHX eliminates nitrate-reducing bacteria, which are essential for NO production. Although endogenous NO production may be insufficient, the nitrate-nitrite-NO pathway plays a critical role in maintaining appropriate endothelial function, which is balanced by the microbiome and dietary nitrate intake. Dietary nitrate supplementation may lead to beneficial changes in the oral microbiome, thereby increasing the NO bioavailability. However, NO bioavailability can be compromised by reactive oxygen species (ROS) and the uncoupling of endothelial nitric oxide synthase (eNOS), leading to further ROS generation and creating a detrimental cycle. Studies on NO and periodontal disease have shown increased nitrite concentrations in patients with periodontal disease, although these studies have some methodological limitations. In terms of blood pressure, literature suggests that CHX mouthrinses may reduce the capacity of nitrate-reducing bacteria, potentially leading to an increase in blood pressure. CONCLUSIONS: Several studies have suggested an association between NO levels and the development of cardiovascular and periodontal diseases. However, the exact mechanisms linking these diseases remains to be fully elucidated. CLINICAL RELEVANCE: Nitric oxide (NO) is a signaling molecule that plays a crucial role in several physiological processes such as vascular homeostasis, inflammation, immune cell activity, and pathologies such as hypertension and periodontitis.

Ultra-Microporous Fe-MOF with Prolonged NO Delivery in Biological Media for Therapeutic Application.

Nitric oxide (NO), a key element in the regulation of essential biological mechanisms, presents huge potential as therapeutic agent in the treatment and prevention of chronic diseases. Metal-organic frameworks (MOFs) with open metal sites are promising carriers for NO therapies but delivering it over an extended period in biological media remains a great challenge due to i) a fast degradation of the material in body fluids and/or ii) a rapid replacement of NO by water molecules onto the Lewis acid sites. Here, a new ultra-narrow pores Fe bisphosphonate MOF, denoted MIP-210(Fe) or Fe(H2O)(Hmbpa) (H4mbpa = p-xylenediphosphonic acid) is described that adsorbs NO due to an unprecedented sorption mechanism: coordination of NO through the Fe(III) sites is unusually preferred, replacing bound water, and creating a stable interaction with the free H2O and P-OH groups delimiting the ultra-narrow pores. This, associated with the high chemical stability of the MOF in body fluids, enables an unprecedented slow replacement of NO by water molecules in biological media, achieving an extraordinarily extended NO delivery time over at least 70 h, exceeding by far the NO kinetics release reported with others porous materials, paving the way for the development of safe and successful gas therapies.