Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21.105
Filtrar
1.
Bol. latinoam. Caribe plantas med. aromát ; 23(4): 516-522, jul. 2024. graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1538029

RESUMO

This article aimed to discuss the protection of trans - nerolidol on vascular endothelial cells (ECs) injured by lipopolysac charides. ECs were divided into four groups: normal, model, low and high dose trans - nerolidol treatment groups. The cell survival rate and the contents of NO in the cell culture supernatant were determined. The protein expression and transcript level of pe roxisome proliferator - activated receptor - γ (PPARγ), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were determined by western blotting and RT - PCR respectively. Compared with the normal group, cell livability, protein e xpression and mRNA transcript level of PPARγ and eNOS decreased, NO contents, protein expression and mRNA transcript tlevel of iNOS increased in model group significantly. Compared with model group, all the changes recovered in different degree in treatmen t groups. Hence, it was concluded that trans - nerolidol can alleviate the ECs injuryby the regulation of iNOS/eNOS through activating PPARγ in a dose - dependent manner


Este artículo tiene como objetivo discutir la protección del trans - nerolidol en las células endoteliales vasculares (CE) dañadas por lipopolisacáridos. Las CE se di vidieron en cuatro grupos: normal, modelo, grupos de tratamiento con trans - nerolidol de baja y alta dosis. Se determinó la tasa de supervivencia de las células y los contenidos de óxido nítrico (NO) en el sobrenadante del cultivo celular. La expresión de p roteínas y el nivel de transcripción del receptor activado por proliferadores de peroxisomas - γ (PPARγ), el óxido nítrico sint et asa endotelial (eNOS) y el óxido nítrico sint et asa inducible (iNOS) se determinaron mediante western blot y RT - PCR, respectivamen te. En comparación con el grupo normal, la viabilidad celular, la expresión de proteínas y el nivel de transcripción de PPARγ y eNOS disminuyeron, los contenidos de NO, la expresión de proteínas y el nivel de transcripción de iNOS aumentaron significativam ente en el grupo modelo. En comparación con el grupo modelo, todos los cambios se recuperaron en diferentes grados en los grupos de tratamiento. Por lo tanto, se concluyó que el trans - nerolidol puede aliviar el daño en las CE regulando iNOS/eNOS a través d e la activación de PPARγ de manera dependiente de la dosis.


Assuntos
Sesquiterpenos/farmacologia , Lipopolissacarídeos/farmacologia , Células Endoteliais/efeitos dos fármacos
2.
Int J Cardiol ; : 132043, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38614366

RESUMO

BACKGROUND: Calcium channel blockers (CCB) are the first effective therapy for vasoreactive patients with idiopathic pulmonary arterial hypertension (IPAH). However, the advent of modern PAH-specific drugs may undermine the role of vasoreactivity tests and CCB treatment. We aimed to clarify the effect of acute vasoreactivity testing and CCB on patients with IPAH receiving PAH-specific treatment. METHODS: We retrospectively investigated consecutive patients with IPAH (n = 136) diagnosed between 2000 and 2020 and collected data from patients who underwent acute vasoreactivity testing using inhaled nitric oxide (NO). The effects of vasoreactivity testing and CCB therapy were reviewed. Long-term survival was analysed using the Kaplan-Meier method. RESULTS: Acute vasoreactivity testing was performed in 49% of patients with IPAH (n = 67), including 23 patients (34%) receiving PAH-specific therapy without vasoreactivity testing. Eight patients (12%), including three patients (4.4%) receiving PAH-specific therapy, presented acute responses at vasoreactivity testing. They received high-dose CCB therapy (CCB monotherapy for five patients [7.5%] and CCB therapy and PAH-specific therapy for three patients [4.4%]). They presented a significant improvement in clinical parameters and near-normalisation of haemodynamics (mean pulmonary arterial pressure decreased from 46 [interquartile range: 40-49] to 19.5 [interquartile range: 18-23] mmHg [P < .001] at 1-year follow-up). All eight vasoreactive responders receiving CCB therapy showed better long-term survival than non-responders treated with PAH-specific therapy (P < .001). CONCLUSIONS: CCB therapy benefited patients with IPAH who showed acute response to vasoreactivity testing using inhaled NO, even when receiving modern PAH-specific therapy. Acute vasoreactive responders may benefit more from CCB than from PAH-specific therapy.

3.
J Exp Bot ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623889

RESUMO

Cassava is one of the most important tuber crops that is used for food, starch and bio-energy. However, cassava is susceptible to a number of diseases, especially cassava bacterial blight (CBB). Nitric oxide (NO) and hydrogen peroxide (H2O2) regulate plant growth and development, as well as stress responses. However, no direct relationships between the enzymes involved in the metabolic enzymes that produce and process these key signaling molecules has been demonstrated. Here, we provide evidence for the interaction between the nitrate reductase 2 (MeNR2) and catalase 1 (MeCAT1) proteins in vitro and in vivo, using yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays, respectively. MeNR2 is a positive regulator and MeCAT1 is a negative regulator of CBB resistance. MeNR2 was localized in the nucleus, cell membrane and peroxisome, while MeCAT1 was localized in the peroxisomes. The interactions between MeNR2 and MeCAT1 also had effects of their respective enzyme activities. Taken together, the data presented here suggested that there is coordination between H2O2 and NO signaling in cassava disease resistance, through the interactions between MeCAT1 and MeNR2.

4.
Cell Rep ; 43(4): 114091, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38607914

RESUMO

Nitric oxide (NO) is a gasotransmitter required in a broad range of mechanisms controlling plant development and stress conditions. However, little is known about the specific role of this signaling molecule during lipid storage in the seeds. Here, we show that NO is accumulated in developing embryos and regulates the fatty acid profile through the stabilization of the basic/leucine zipper transcription factor bZIP67. NO and nitro-linolenic acid target and accumulate bZIP67 to induce the downstream expression of FAD3 desaturase, which is misregulated in a non-nitrosylable version of the protein. Moreover, the post-translational modification of bZIP67 is reversible by the trans-denitrosylation activity of peroxiredoxin IIE and defines a feedback mechanism for bZIP67 redox regulation. These findings provide a molecular framework to control the seed fatty acid profile caused by NO, and evidence of the in vivo functionality of nitro-fatty acids during plant developmental signaling.

5.
Brain Res ; : 148935, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38609031

RESUMO

OBJECTIVES: Impulsive behavior is the precursor of many psychiatric and neurological conditions. High levels of impulsive behavior will increase health risk behavior and related injuries. Impulsive behavior is produced and regulated by central and peripheral biological factors, and oxidative stress (OS) can aggravate it. However, previous studies only showed that impulsive behavior was related to the level of the peripheral OS. Therefore, this study aims to clarify the relationship between OS and impulsive behavior in the brain and peripheral blood. METHODS: We recruited 64 Chinese men. We measured superoxide dismutase (SOD) (including copper, zinc and manganese) and nitric oxide synthase (NOS) (including total, inducible and constitutive) in cerebrospinal fluid (CSF) and plasma. The Barratt Impulsiveness Scale version 11 (BIS-11) was used to evaluate impulsive behavior. The relationship between OS and impulsive behavior was evaluated by partial correlation analysis and stepwise multiple regression analysis. RESULTS: Partial correlation analysis showed that the ratio of total NOS-to-MnSOD and iNOS-to-MnSOD in CSF were negatively correlated with the BIS-11 motor scores (r = -0.431, p = -0.001; r = -0.434, p = -0.001). Stepwise multiple regression analysis showed that the ratio of CSF iNOS-to-MnSOD was the most influential variable on the BIS-11 motor scores(ß = -0.434, t = -3.433, 95 %CI(-0.374, -0.098), p = 0.001). CONCLUSIONS AND RELEVANCE: The imbalance of central oxidation and antioxidation is related to impulsive behavior, which broadens our understanding of the correlation between impulsive behavior and OS.

6.
Toxicon ; : 107716, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38614247

RESUMO

The phagocytic activity of macrophages activated with MT-II, a Lys-49 PLA2 homolog, and MT-III, an Asp-49 PLA2, from Bothrops asper snake venom, was investigated in this study using a pharmacological approach. Stimulating thioglycollate-elicited macrophages with both venom components enhanced their ability to phagocytose non-opsonized zymosan particles. MT-II and MT-III-induced phagocytosis was drastically inhibited by pretreating cells with L-NAME, aminoguanidine or L-NIL, cNOS or iNOS inhibitors, or with ODQ (sGC inhibitor) or Rp-cGMPS (PKG inhibitor). These results indicate that the NO/sGC/GMP/PKG pathway plays an essential role in the ß-glucan-mediated phagocytosis induced in macrophages by these venom-secretory PLA2s.

7.
Acta Biomater ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38614415

RESUMO

Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. Herein, a dual functional submicron textured nitric oxide (NO)-releasing catheter was developed. The hemocompatibility and antithrombotic activity of vascular catheters were evaluated in both 20 h in vitro blood loop and 7 d in vivo rabbit model. Surface characterization assessments via atomic force microscopy show the durability of the submicron pattern after incorporation of NO donor S-nitroso-N-acetylpenicillamine (SNAP). The SNAP-doped catheters exhibited prolonged and controlled NO release mimicking the levels released by endothelium. Fabricated catheters showed cytocompatibility when evaluated against BJ human fibroblast cell lines. After 20h in vitro evaluation of catheters in a blood loop, textured-NO catheters exhibited a 13-times reduction in surface thrombus formation compared to the control catheters, which had 83% of the total area covered by clots. After the 7 d in vivo rabbit model, analysis on the catheter surface was examined via scanning electron microscopy, where significant reduction of platelet adhesion, fibrin mesh, and thrombi can be observed on the NO-releasing textured surfaces. Moreover, compared to relative controls, a 63% reduction in the degree of thrombus formation within the jugular vein was observed. Decreased levels of fibrotic tissue decomposition on the jugular vein and reduced platelet adhesion and thrombus formation on the texture of the NO-releasing catheter surface are indications of mitigated foreign body response. This study demonstrated a biocompatible and robust dual-functioning textured NO PU catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. STATEMENT OF SIGNIFICANCE: Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. This study demonstrated a robust, biocompatible, dual-functioning textured nitric oxide (NO) polyurethane catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. The fabricated catheters exhibited prolonged and controlled NO release that mimics endothelium levels. After the 7 d in vivo model, a significant reduction in platelet adhesion, fibrin mesh, and thrombi was observed on the NO-releasing textured catheters, along with decreased levels of fibrotic tissue decomposition on the jugular vein. Results illustrate that NO-textured catheter surface mitigates foreign body response.

8.
Front Physiol ; 15: 1338476, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628440

RESUMO

Introduction: Erythropoietin (EPO) acts primarily in regulating red blood cell production mediated by high EPO receptor (EPOR) expression in erythroid progenitor cells. EPO activity in non-erythroid tissue is evident in mice with EPOR restricted to erythroid tissues (ΔEPORE) that become obese, glucose-intolerant, and insulin-resistant. In animal models, nitric oxide synthase (NOS) contributes to EPO activities including erythropoiesis, neuroprotection, and cardioprotection against ischemia-reperfusion injury. However, we found that extended EPO treatment to increase hematocrit compromised heart function, while the loss of neuronal NOS (nNOS) was protective against the deleterious activity of EPO to promote heart failure. Methods: Wild-type (WT) mice, ΔEPORE mice, and nNOS-knockout mice (nNOS-/-) were placed on a high-fat diet to match the ΔEPORE obese phenotype and were treated with EPO for 3 weeks. Hematocrit and metabolic response to EPO treatment were monitored. Cardiac function was assessed by echocardiography and ultrasonography. Results: ΔEPORE mice showed a decrease in the left ventricular outflow tract (LVOT) peak velocity, ejection fraction, and fractional shortening, showing that endogenous non-erythroid EPO response is protective for heart function. EPO treatment increased hematocrit in all mice and decreased fat mass in male WT, demonstrating that EPO regulation of fat mass requires non-erythroid EPOR. EPO treatment also compromised heart function in WT mice, and decreased the pulmonary artery peak velocity (PA peak velocity), LVOT peak velocity, ejection fraction, and fractional shortening, but it had minimal effect in further reducing the heart function in ΔEPORE mice, indicating that the adverse effect of EPO on heart function is not related to EPO-stimulated erythropoiesis. ΔEPORE mice had increased expression of heart failure-associated genes, hypertrophic cardiomyopathy-related genes, and sarcomeric genes that were also elevated with EPO treatment in WT mice. Male and female nNOS-/- mice were protected against diet-induced obesity. EPO treatment in nNOS-/- mice increased the hematocrit that tended to be lower than WT mice and decreased the PA peak velocity but did not affect the LVOT peak velocity, ejection fraction, and fractional shortening, suggesting that nNOS is required for the adverse effect of EPO treatment on heart function in WT mice. EPO treatment did not change expression of heart failure-associated gene expression in nNOS-/- mice. Discussion: Endogenous EPO has a protective effect on heart function. With EPO administration, in contrast to the protective effect to the cardiac injury of acute EPO treatment, extended EPO treatment to increase hematocrit in WT mice adversely affected the heart function with a corresponding increase in expression of heart failure-associated genes. This EPO activity was independent of EPO-stimulated erythropoiesis and required EPOR in non-erythroid tissue and nNOS activity, while nNOS-/- mice were protected from the EPO-associated adverse effect on heart function. These data provide evidence that nNOS contributes to the negative impact on the heart function of high-dose EPO treatment for anemia.

9.
Nitric Oxide ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631610

RESUMO

Nitric oxide (NO) donating drugs such as organic nitrates have been used to treat cardiovascular diseases for more than a century. These donors primarily produce NO systemically. It is however sometimes desirable to control the amount, location, and time of NO delivery. We present the design of a novel pH-sensitive NO release system that is achieved by the synthesis of dipeptide diphenylalanine (FF) and graphene oxide (GO) co-assembled hybrid nanosheets (termed as FF@GO) through weak molecular interactions. These hybrid nanosheets are characterised by using X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, zeta potential measurements, X-ray photoelectron spectroscopy, scanning and transmission electron microscopies. The weak molecular interactions, which include electrostatic, hydrogen bonding and π-π stacking, are pH sensitive due to the presence of carboxylic acid and amine functionalities on GO and the dipeptide building blocks. Herein, we demonstrate that this formulation can be loaded with NO gas with the dipeptide acting as an arresting agent to inhibit NO burst release at neutral pH; however, at acidic pH it is capable of releasing NO at the rate of up to 0.6 µM per minute, comparable to the amount of NO produced by healthy endothelium. In conclusion, the innovative conjugation of dipeptide with graphene can store and release NO gas under physiologically relevant concentrations in a pH-responsive manner. pH responsive NO-releasing organic-inorganic nanohybrids may prove useful for the treatment of cardiovascular diseases and other pathologies.

10.
BMC Pulm Med ; 24(1): 178, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622520

RESUMO

BACKGROUND: Asthma is a common disease characterized by chronic inflammation of the lower airways, bronchial hyperactivity, and (reversible) airway obstruction. The Global Initiative of Asthma Guideline recommends a flowchart to diagnose asthma with first-step spirometry with reversibility and a bronchial challenge test (BPT) with histamine or methacholine as a second step [1]. The BPT is considered burdensome, time-consuming for patients and staff, can cause side effects, and is expensive. In addition, this test strongly encumbers lung function capacity. Elevated Nitric Oxide (NO) is associated with airway eosinophilic inflammation in asthma patients and can be measured in exhaled air with the Fractional exhaled (Fe) NO-test. This low-burden FeNO-test could be used as an 'add-on' test in asthma diagnostics [2, 3]. METHODS AND ANALYSIS: This multi-center prospective study (Trial number: NCT06230458) compares the 'standard asthma diagnostic work-up' (spirometry with reversibility and BPT) to the 'new asthma diagnostics work-up' (FeNO-test as an intermediate step between the spirometry with reversibility and the BPT), intending to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness and reduced burden to the patient and health care. The cost reduction of incorporating the FeNO-test in the new diagnostic algorithm will be established by the number of theoretically avoided BPT. The decrease in burden will be studied by calculating differences in the Visual Analogue Scale (VAS) -score and Asthma Quality of Life Questionnaire (AQLQ) -score after the BPT and FeNO-test with an independent T-test. The accuracy of the FeNO-test will be calculated by comparing the FeNO-test outcomes to the (gold standard) BPTs outcomes in terms of sensitivity and specificity. The intention is to include 171 patients. ETHICS AND DISSEMINATION: The local medical ethics committee approved the proposed study and is considered a low-burden and risk-low study. The local medical ethics committee registration number: R23.005. STRENGTHS AND LIMITATIONS OF THIS STUDY: Strengths: This is the first study that investigates the value of the FeNO-test (cut off ≥ 50 ppb) as an add-on test, to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness, and reduced burden on the patient and health care. LIMITATIONS: High FeNO levels may also be observed in other diseases such as eosinophilic chronic bronchitis and allergic rhinitis. The FeNO-test can be used to rule in a diagnosis of asthma with confidence, however, due to the poor sensitivity it is not suitable to rule out asthma.


Assuntos
Asma , Bronquite Crônica , Humanos , Teste da Fração de Óxido Nítrico Exalado , Estudos Prospectivos , Qualidade de Vida , Testes Respiratórios , Asma/tratamento farmacológico , Óxido Nítrico , Inflamação , Estudos Multicêntricos como Assunto
11.
Curr Res Food Sci ; 8: 100731, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38623273

RESUMO

Nitrates and nitrites, which are synthetic additives, are traditionally used as curing agents in meat-based products. These synthetic additives are employed in the preparation of fermented meat foods to improve quality characteristics and microbiological safety, develop distinct flavours and red-colour stability, and counteract lipid oxidation. Nitrites also display significant bacteriostatic and bactericidal action against spoilage microorganisms and foodborne pathogens (such as Clostridium botulinum and Listeria monocytogenes). However, meat curing is currently under scrutiny because of its links to cardiovascular diseases and colorectal cancer. Based on the current literature, this review provides recent scientific evidence on the potential utilisation of coagulase-negative staphylococci (CNS) as nitrate and nitrite substitutes in meat-based foods. Indeed, CNS are reported to reproduce the characteristic red pigmentation and maintain the typical high-quality traits of cured-meats, thanks to their arginine degradation pathway, thus providing the nitrite-related desirable attributes in cured meat. The alternative strategy, still based on the NOS pathway, consisting of supplementing meat with arginine to release nitric oxide (NO) and obtain a meat characterised by the desired pinkish-red colour, is also reviewed. Exploiting NOS-positive CNS strains seems particularly challenging because of CNS technological adaptation and the oxygen dependency of the NOS reaction; however, this exploitation could represent a turning point in replacing nitrates and nitrites in meat foods.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38635146

RESUMO

Eccentric contraction (ECC) has been shown to induce leukocyte invasion into skeletal muscle, resulting in muscle inflammation. This study aimed to investigate whether prior ingestion of L-arginine (ARG), a nitric oxide precursor, inhibits ECC-induced macrophage invasion. Male Wistar rats received ARG in water for 7 days, beginning 3 days prior to ECC. ECCs were induced in the anterior crural muscles for 200 cycles. Three days later, the tibialis anterior and extensor digitorum longus muscles were excised for biochemical analysis and force measurement, respectively. ARG ingestion increased nitrite and nitrate levels in plasma and muscle, inhibiting force depression and reducing CD68 content in muscles subjected to ECC. ARG ingestion also ameliorated an ECC-induced increase in protein nitration, although neither ARG ingestion nor ECC induction affected protein carbonyl levels. The present results suggest that ingestion of ARG or ARG-rich foods may alleviate inflammation by attenuating phagocyte invasion in eccentrically contracted skeletal muscles.

13.
J Ovarian Res ; 17(1): 77, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594780

RESUMO

PURPOSE: Our explorative study assessed a panel of molecules for their association with epithelial ovarian carcinomas and their prognostic implications. The panel included tissue expression of VEGF-C, COX-2, Ki-67 and eNOS alongside plasma levels of VEGF-C and nitric oxide. METHODS: 130 cases were enrolled in the study. Plasma levels were quantified by ELISA and tissue expressions were scored by immunohistochemistry. The Chi square and Fischer's exact test were applied to examine the impact of markers on clinicopathological factors. Non-parametric Spearman's rank correlation test was applied to define the association among test factors. RESULTS: Plasma VEGF-C levels and COX-2 tissue expression strongly predicted recurrence and poor prognosis (< 0.001). Tissue Ki-67 was strongly indicative of late-stage disease (< 0.001). The aforementioned markers significantly associated with clinicopathological factors. Nuclear staining of VEGF-C was intriguing and was observed to correlate with high grade-stage malignancies, highly elevated plasma VEGF-C, and with recurrence. eNOS tissue expression showed no significant impact while nitric oxide associated positively with ascites levels. Tissue expression of VEGF-C did not associate significantly with poor prognosis although the expression was highly upregulated in most of the cases. CONCLUSION: Plasma VEGF-C holds immense promise as a prognostic marker and the nuclear staining of VEGF-C seems to have some significant implication in molecular carcinogenesis and is a novel finding that commands further robust scrutiny. We present a first such study that assesses a set of biomarkers for prognostic implications in clinical management of epithelial ovarian carcinomas in a pan-Indian (Asian) population.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/patologia , Prognóstico , Neoplasias Ovarianas/patologia , Ciclo-Oxigenase 2/metabolismo , Fator C de Crescimento do Endotélio Vascular , Antígeno Ki-67 , Óxido Nítrico , Estadiamento de Neoplasias , Biomarcadores Tumorais/metabolismo
14.
ACS Sens ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593007

RESUMO

Gasotransmitters, including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), are a class of gaseous, endogenous signaling molecules that interact with one another in the regulation of critical cardiovascular, immune, and neurological processes. The development of analytical sensing mechanisms for gasotransmitters, especially multianalyte mechanisms, holds vast importance and constitutes a growing area of study. This review provides an overview of electrochemical sensing mechanisms with an emphasis on opportunities in multianalyte sensing. Electrochemical methods demonstrate good sensitivity, adequate selectivity, and the most well-developed potential for the multianalyte detection of gasotransmitters. Future research will likely address challenges with sensor stability and biocompatibility (i.e., sensor lifetime and cytotoxicity), sensor miniaturization, and multianalyte detection in biological settings.

15.
ACS Appl Bio Mater ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593411

RESUMO

Bacterial biofilms play a central role in the development and progression of periodontitis, a chronic inflammatory condition that affects the oral cavity. One solution to current treatment constraints is using nitric oxide (NO)─with inherent antimicrobial properties. In this study, an antimicrobial coating is developed from the NO donor S-nitroso-N-acetylpenicillamine (SNAP) embedded within polyethylene glycol (PEG) to prevent periodontitis. The SNAP-PEG coating design enabled a controlled NO release, achieving tunable NO levels for more than 24 h. Testing the SNAP-PEG composite on dental floss showed its effectiveness as a uniform and bioactive coating. The coating exhibited antibacterial properties against Streptococcus mutans and Escherichia coli, with inhibition zones measuring up to 7.50 ± 0.28 and 14.80 ± 0.46 mm2, respectively. Furthermore, SNAP-PEG coating materials were found to be stable when stored at room temperature, with 93.65% of SNAP remaining after 28 d. The coatings were biocompatible against HGF and hFOB 1.19 cells through a 24 h controlled release study. This study presents a facile method to utilize controlled NO release with dental antimicrobial coatings comprising SNAP-PEG. This coating can be easily applied to various substrates, providing a user-friendly approach for targeted self-care in managing gingival infections associated with periodontitis.

16.
Biochem J ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592741

RESUMO

Knowledge of the primary structure of neuronal NO synthase (nNOS) in skeletal muscle is still conflicting and needs further clarification. To elucidate the expression patterns of nNOS isoforms at both mRNA and protein level, systematic RT-PCR and epitope mapping by qualitative immunoblot analysis on skeletal muscle of C57/BL6 mice were performed. The ability of the nNOS isoforms to form aggregates was characterized by native low-temperature polyacrylamide electrophoresis (LT-PAGE). The molecular analysis was focused on the rectus femoris (RF) muscle, a skeletal muscle with a nearly balanced ratio of nNOS alpha- and beta-isoforms. RT-PCR amplificates from RF muscles showed exclusive exon-1d mRNA expression, either with or without exon-mu. Epitope mapping demonstrated the simultaneous expression of the nNOS splice variants alpha/mu, alpha/non-mu, beta/mu and beta/non-mu. Furthermore, immunoblotting suggests that the transition between nNOS alpha- and beta-isoforms lies within exon-3. In LT-PAGE, three protein nNOS associated aggregates iwere detected in homogenates of RF muscle and tibialis anterior muscle: a 320 kDa band containing nNOS alpha-isoforms, while 250 kDa and 300 kDa bands consist of nNOS beta-isoforms that form homodimers or heterodimers with non-nNOS proteins.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38586887

RESUMO

Nitric oxide is produced at low micromolar levels following the induction of inducible nitric oxide synthase (iNOS) and is responsible for mediating the inhibitory actions of cytokines on glucose-stimulated insulin secretion by islets of Langerhans. It is through the inhibition of mitochondrial oxidative metabolism, specifically aconitase and complex 4 of the electron transport chain, that nitric oxide inhibits insulin secretion. Nitric oxide also attenuates protein synthesis, induces DNA damage, activates DNA repair pathways, and stimulates stress responses (unfolded protein and heat shock) in ß-cells. In this report, the time- and concentration-dependent effects of nitric oxide on the expression of 6 genes known to participate in the response of ß-cells to this free radical were examined. The genes included Gadd45α (DNA repair), Puma (apoptosis), Hmox1 (antioxidant defense), Hsp70 (heat shock), Chop (UPR), and ßPpargc1α (mitochondrial biogenesis). We show that nitric oxide stimulates ß-cell gene expression in a narrow concentration range of ~0.5-1 µM, or levels corresponding to iNOS-derived nitric oxide. At concentrations greater than 1 µM, nitric oxide fails to stimulate gene expression in ß-cells, and this is associated with the inhibition of mitochondrial oxidative metabolism. This narrow concentration range of responses is ß-cell selective, as the actions of nitric oxide in non-ß-cells (α-cells, mouse embryonic fibroblasts, and macrophages) are concentration-dependent. Our findings suggest that ß-cells respond to a narrow concentration range of nitric oxide that is consistent with the levels produced following iNOS induction, and that these concentration-dependent actions are selective for insulin-containing cells.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38587367

RESUMO

Whether S-nitrosylation is the result of an unselective chemical process or enzymatically driven has been debated for years. A recent study by Zhou et al. identifies and characterizes the first S-nitroso-CoA (SNO-CoA)-assisted nitrosylase (SCAN) that catalyzes protein S-nitrosylation in mammals, including insulin receptor (INSR)/insulin receptor substrate 1 (IRS1), with implications for human metabolism.

19.
Nitric Oxide ; 146: 37-47, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38579899

RESUMO

AIM: The mechanism of NO bioavailability in endothelial dysfunction, the trigger for atherogenesis is still unclear as exogenous nitrate therapy fails to alleviate endothelial dysfunction. Recently, sialin, a nitrate transporter, has been linked to affect tissue nitrate/nitrite levels. Hence, we investigated the role of sialin in NO bioavailability in endothelial dysfunction. METHODS: Serum-starved HUVECs were stimulated with either TNFα or AT-2 for 24 h either alone or in the presence of autophagy inducer or autophagy inhibitor alone. Nitric oxide, nitrite, and nitrate levels were measured in cell supernatant and cell lysate. Quantitative real-time PCR, Annexin V-PI, and monocyte adhesion assays were performed. Immunofluorescence staining for sialin, vWF, and LC3 was performed. STRING database was used to create protein interacting partners for sialin. RESULTS: Sialin is strongly expressed in activated EC in vitro and atherosclerotic plaque as well as tumor neo-vessel ECs. Sialin mediates nitrate ion efflux and is negatively regulated by autophagy via mTOR pathway. Blocking sialin enhances NO bioavailability, autophagy, cell survival, and eNOS expression while decreasing monocyte adhesion. PPI shows LGALS8 to directly interact with sialin and regulate autophagy, cell-cell adhesion, and apoptosis. CONCLUSION: Sialin is a potential novel therapeutic target for treating endothelial dysfunction in atherosclerosis and cancer.

20.
Molecules ; 29(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38611909

RESUMO

Dinitrosyl iron complexes (DNICs) stabilize nitric oxide in cells and tissues and constitute an important form of its storage and transportation. DNICs may comprise low-molecular-weight ligands, e.g., thiols, imidazole groups in chemical compounds with low molecular weight (LMWDNICs), or high-molecular-weight ligands, e.g., peptides or proteins (HMWDNICs). The aim of this study was to investigate the role of low- and high-molecular-weight ligands in DNIC formation. Lysosomal and proteasomal proteolysis was inhibited by specific inhibitors. Experiments were conducted on human erythroid K562 cells and on K562 cells overexpressing a heavy chain of ferritin. Cell cultures were treated with •NO donor. DNIC formation was monitored by electron paramagnetic resonance. Pretreatment of cells with proteolysis inhibitors diminished the intensity and changed the shape of the DNIC-specific EPR signal in a treatment time-dependent manner. The level of DNIC formation was significantly influenced by the presence of protein degradation products. Interestingly, formation of HMWDNICs depended on the availability of LMWDNICs. The extent of glutathione involvement in the in vivo formation of DNICs is minor yet noticeable, aligning with our prior research findings.


Assuntos
Óxido Nítrico , Óxidos de Nitrogênio , Humanos , Proteólise , Óxidos de Nitrogênio/farmacologia , Ferro
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...