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[Display omitted] Pathogen contamination in drinking water sources causes waterborne infectious diseases, seriously threatening human health. Nowadays, stimuli-responsive self-propelled nanomotors are appealing therapeutic agents for antibacterial therapy in vivo. However, achieving water disinfection using these nanobots is still a great challenge. Herein, we report on prebiotic galactooligosaccharide-based nanomotors for sunlight-regulated water disinfection. The nanomotors can utilize galactooligosaccharide-based N -nitrosamines as sunlight-responsive fuels for the spontaneous production of antibacterial nitric oxide. Such a solar-to-chemical energy conversion would power the nanomotors for self-diffusiophoresis, which could promote the diffusion of the nanomotors in water and their penetration in the biofilm, significantly enhancing the inhibition and elimination of the pathogens and their biofilms in aquatic environments. After water treatments, the prebiotic-based residual disinfectants can be selectively utilized by beneficial bacteria to effectively relieve safety risks to the environment and human health. The low-energy-cost, green and potent antibacterial nanobots show promising potential in water disinfection. [ABSTRACT FROM AUTHOR]

Nitrosyl iron complexes (NICs) are natural depots of NO. NICs are formed by the interaction of endogenous nitric oxide (NO) and non‒heme [2Fe–2S] proteins. Their synthetic analogues are promising compounds in medicines for the treatment of socially significant diseases. In this paper, the effect of bovine serum albumin (BSA) and reduced glutathione (GSH) on the decomposition of a nitrosyl iron complex with N,N'-dimethylthiourea ligands [Fe(SC(NHCH3)2)2(NO)2]BF4 (complex 1) under aerobic conditions are studied. In the absorption spectra complex 1 in the presence of albumin a wide band appears at 370–410 nm, which indicates the coordination of the aerobic decay product of the complex in the hydrophobic pocket of the protein with Cys34 and His39. The quenching of albumin's intrinsic fluorescence during titration with complex 1 is studied by fluorescence spectroscopy. The Stern–Volmer constant K = (2.3 ± 0.2) × 105 М–1 and the Förster radius 22.4 Å are calculated. The UV-spectrum of complex 1 in the presence of GSH has two peaks at 312 and 363 nm, characteristic of glutathione binuclear NICs. [ABSTRACT FROM AUTHOR]

• Hypodynamic chronic hypertension is associated to pregnancy complications in about 80% of cases. • Hypodynamic circulation might be improved adding NO donors and Oral Fluids to standard treatment. • The tailored treatment of hypodynamic circulation might reduce pregnancy complications. Chronic hypertension is associated with significant adverse maternal and fetal outcomes that appear to be often associated to a hypodynamic circulation. Treatment of hypertensive disorders of pregnancy tailored on maternal hemodynamics might reduce or mitigate these complications. Our purpose was to assess the hemodynamic modifications induced by the addition of NO donors and increased oral fluid intake on top of standard antihypertensive therapy in hypodynamic chronic hypertensive patients. We further evaluated if the possible hemodynamic modification induced by NO donors and increased oral fluid intake might be associated to a reduction of the severity and rate of complications vs. patients on antihypertensive standard treatment. This was a case-control study of 321 chronic hypertensive patients with a hypodynamic circulation at the echocardiographic evaluation at 24 weeks' gestation. We included 160 controls (standard antihypertensive therapy) and 161 cases (standard therapy + NO donor patches + increased oral fluid intake). Student T test for paired and unpaired data, univariate logistic regression analysis, ROC curve analysis, and Cox Hazards Regression analysis were used as appropriate. At enrollment the hemodynamic parameters were similar between the two groups. After 3–4 weeks stroke volume (77 ± 19 mL vs. 69 ± 19 mL; p < 0.001), and cardiac output (6.2 ± 1.7 L vs. 5.0 ± 1.6 L; p < 0.001) were higher and total peripheral vascular resistance (1465 ± 469 dyne·s·cm−5 vs. 1814 ± 524 dyne·s·cm−5; p < 0.001) was lower in the cases vs controls. Superimposed preeclampsia, preterm delivery before 34 weeks, abruptio placentae, HELLP Syndrome, fetal growth restriction, and perinatal death were more represented in the standard treatment group vs NO treated patients (81% vs 53%; p < 0.001). In particular, the standard treatment group showed 48% fetal growth restriction vs 34% in the NO treated group (p < 0.011). The Cox proportional-hazards regression showed a lower proportion of event-free pregnancies in controls on standard treatment (HR 2.6; 95% CI 2.0–3.5; p < 0.0001), and a prolongation of pregnancies in CH cases complicated by fetal growth restriction taking NO donors (HR 0.29; 95% CI 0.19–0.43; p = 0.0001). The tailored treatment with NO donors and oral fluids of hypodynamic CH might have positive effects on the reduction or mitigations of adverse outcomes. [ABSTRACT FROM AUTHOR]

A facile and efficient method for the regioselective [3 + 2] cycloaddition of 4-azidofuroxans to 1-dimethylamino-2-nitroethylene under p-TSA catalysis affording (4-nitro-1,2,3-triazolyl)furoxans was developed. This transformation is believed to proceed via eliminative azide–olefin cycloaddition resulting in its complete regioselectivity. The developed protocol has a broad substrate scope and enables a straightforward assembly of the 4-nitro-1,2,3-triazole motif. Moreover, synthesized (4-nitro-1,2,3-triazolyl)furoxans were found to be capable of NO release in a broad range of concentrations, thus providing a novel platform for future drug design and related biomedical applications of heterocyclic NO donors. [ABSTRACT FROM AUTHOR]

Two new 4-methylcoumarin derivatives (3a–f and 4a–f) were designed, synthesized, and evaluated for their cytotoxic activity. Different spectroscopic methods and elemental analyses confirmed all the synthesized derivatives' characterization. All the prepared compounds were biologically screened against four cancer cell lines (hepatocellular carcinoma HepG-2, colon cancer cell lines HCT-116, breast cancer cell lines MCF-7, and prostate cancer cell lines PC3). The in vitro antiproliferative activity of the target analogues 4b, 4c, 4f, 3b, and 3d against the MCF-7 cancer cell line was significant, with IC50 values of 3.98, 7.80, 10.94, 17.7, and 24.07 μM, respectively. Furthermore, the potent cytotoxic oxime derivative 4b was evaluated for cell cycle analysis showing a significant substantial disruption in cell cycle profile and cell cycle arrest at the S phase boundary with a time-dependent rise in a pre-G cell population, as well as a 22-fold increase in MCF-7 apoptosis compared to control cells. Accordingly, the Bax/Bcl-2 ratio, a critical ratio in controlling cell sensitivity to apoptosis, increased upon treatment with the oxime analog 4b. A docking investigation was conducted within the BcL-2 binding site to explore and anticipate the binding modes of the synthesized compounds. Thus, synthesizing these novel coumarin/nitric oxide hybrids may aid in developing promising antiproliferative agents. [ABSTRACT FROM AUTHOR]

Lung transplantation is an evolutionary procedure from its experimental origin in the twentieth century and is now recognized as an established and routine life-saving intervention for a variety of end-stage pulmonary diseases refractory to medical management. Despite the success and continuous refinement in lung transplantation techniques, the widespread application of this important life-saving intervention is severely hampered by poor allograft quality offered from donors-after-brain-death. This has necessitated the use of lung allografts from donors-after-cardiac-death (DCD) as an additional source to expand the pool of donor lungs. Remarkably, the lung exhibits unique properties that may make it ideally suitable for DCD lung transplantation. However, primary graft dysfunction (PGD), allograft rejection and other post-transplant complications arising from unavoidable ischemia-reperfusion injury (IRI) of transplanted lungs, increase morbidity and mortality of lung transplant recipients annually. In the light of this, nitric oxide (NO), a selective pulmonary vasodilator, has been identified as a suitable agent that attenuates lung IRI and prevents PGD when administered directly to lung donors prior to donor lung procurement, or to recipients during and after transplantation, or administered indirectly by supplementing lung preservation solutions. This review presents a historical account of clinical lung transplantation and discusses the lung as an ideal organ for DCD. Next, the author highlights IRI and its clinical effects in lung transplantation. Finally, the author discusses preservation solutions suitable for lung transplantation, and the protective effects and mechanisms of NO in experimental and clinical lung transplantation.

Fluorescent probes: 8-anilino-1-naphthalenesulfonate (ANS), eosin Y, and pyrene were used to study the interaction between liposomes and three nitrosyl iron complexes that are promising anti-inflammatory agents and cardioprotectors. It was shown that the studied complexes compete with ANS molecules for the bonding sites in a bilayer of liposomes. The incorporation of the complexes into the lipid bilayer was also studied according to the quenching of eosin Y and pyrene fluorescence. The data suggest that iron nitrosyl complexes interact with the phospholipids headgroups and can penetrate deeper into the hydrophobic center of a lipid bilayer, where they affect the packing of fatty acid chains. The pronounced membranotropic properties of the complexes correlated with their ability to inhibit lipid peroxidation. Complexes with high constants of pyrene bonding are the most effective antioxidants. [ABSTRACT FROM AUTHOR]

A facile and efficient method for the regioselective [3 + 2] cycloaddition of 4-azidofuroxans to 1-dimethylamino-2-nitroethylene under p-TSA catalysis affording (4-nitro-1,2,3-triazolyl)furoxans was developed. This transformation is believed to proceed via eliminative azide–olefin cycloaddition resulting in its complete regioselectivity. The developed protocol has a broad substrate scope and enables a straightforward assembly of the 4-nitro-1,2,3-triazole motif. Moreover, synthesized (4-nitro-1,2,3-triazolyl)furoxans were found to be capable of NO release in a broad range of concentrations, thus providing a novel platform for future drug design and related biomedical applications of heterocyclic NO donors.

Environmental pollutants like heavy metals are toxic, persistent, and bioaccumulative in nature. Contamination of agricultural fields with heavy metals not only hampers the quality and yield of crops but also poses a serious threat to human health by entering the food chain. Plants generally cope with heavy metal stress by regulating their redox machinery. In this context, nitric oxide (NO) plays a potent role in combating heavy metal toxicity in plants. Studies have shown that the exogenous application of NO donors protects plants against the deleterious effects of heavy metals by enhancing their antioxidative defense system. Most of the studies have used sodium nitroprusside (SNP) as a NO donor for combating heavy metal stress despite the associated concerns related to cyanide release. Recently, NO-releasing nanoparticles have been tested for their efficacy in a few plants and other biomedical research applications suggesting their use as an alternative to chemical NO donors with the advantage of safe, slow and prolonged release of NO. This suggests that they may also serve as potential candidates in mitigating heavy metal stress in plants. Therefore, this review presents the role of NO, the application of chemical NO donors, potential advantages of NO-releasing nanoparticles, and other NO-release strategies in biomedical research that may be useful in mitigating heavy metal stress in plants. [ABSTRACT FROM AUTHOR]

COX-2 can be considered as a clinically relevant molecular target for adjuvant, in particular radiosensitizing treatments. In this regard, using selective COX-2 inhibitors, e.g., in combination with radiotherapy or endoradiotherapy, represents an interesting treatment option. Based on our own findings that nitric oxide (NO)-releasing and celecoxib-derived COX-2 inhibitors (COXIBs) showed promising radiosensitizing effects in vitro, we herein present the development of a series of eight novel NO-COXIBs differing in the peripheral substitution pattern and their chemical and in vitro characterization. COX-1 and COX-2 inhibition potency was found to be comparable to the lead NO-COXIBs, and NO-releasing properties were demonstrated to be mainly influenced by the substituent in 4-position of the pyrazole (Cl vs. H). Introduction of the N-propionamide at the sulfamoyl residue as a potential prodrug strategy lowered lipophilicity markedly and abolished COX inhibition while NO-releasing properties were not markedly influenced. NO-COXIBs were tested in vitro for a combination with single-dose external X-ray irradiation as well as [177Lu]LuCl3 treatment in HIF2α-positive mouse pheochromocytoma (MPC-HIF2a) tumor spheroids. When applied directly before X-ray irradiation or 177Lu treatment, NO-COXIBs showed radioprotective effects, as did celecoxib, which was used as a control. Radiosensitizing effects were observed when applied shortly after X-ray irradiation. Overall, the NO-COXIBs were found to be more radioprotective compared with celecoxib, which does not warrant further preclinical studies with the NO-COXIBs for the treatment of pheochromocytoma. However, evaluation as radioprotective agents for healthy tissues could be considered for the NO-COXIBs developed here, especially when used directly before irradiation. [ABSTRACT FROM AUTHOR]

Environmental pollutants like heavy metals are toxic, persistent, and bioaccumulative in nature. Contamination of agricultural fields with heavy metals not only hampers the quality and yield of crops but also poses a serious threat to human health by entering the food chain. Plants generally cope with heavy metal stress by regulating their redox machinery. In this context, nitric oxide (NO) plays a potent role in combating heavy metal toxicity in plants. Studies have shown that the exogenous application of NO donors protects plants against the deleterious effects of heavy metals by enhancing their antioxidative defense system. Most of the studies have used sodium nitroprusside (SNP) as a NO donor for combating heavy metal stress despite the associated concerns related to cyanide release. Recently, NO-releasing nanoparticles have been tested for their efficacy in a few plants and other biomedical research applications suggesting their use as an alternative to chemical NO donors with the advantage of safe, slow and prolonged release of NO. This suggests that they may also serve as potential candidates in mitigating heavy metal stress in plants. Therefore, this review presents the role of NO, the application of chemical NO donors, potential advantages of NO-releasing nanoparticles, and other NO-release strategies in biomedical research that may be useful in mitigating heavy metal stress in plants.

Cyclocarya paliurus is commonly used to treat diabetes in China. However, the natural habitats of C. paliurus are typically affected by salt stress. Previous studies showed that nitric oxide (NO) level was related to salt tolerance of C. paliurus, and its synthesis was induced by exogenous hydrogen sulfide. However, the effects of different NO donors in alleviating the negative effect of salt stress are still unclear. In the present study, C. paliurus seedlings pretreated with three NO donors (S-nitroso-N-acetylpenicillamine, SNAP and S-nitrosoglutathione, GSNO and sodium nitroprusside, SNP) were exposed to salt stress, and then, the total biomass, chlorophyll fluorescence parameters, NO and glutathione levels, oxidative damage, and antioxidant enzyme activities were investigated. The results showed that pretreatment of NO donors maintained chlorophyll fluorescence and attenuated the loss of plant biomass under salt stress, and the best performance was observed in C. paliurus under SNP treatment. We also found that pretreatment of NO donors further increased the endogenous NO content and nitrate reductase (NR) activity compared with salt treatment. Moreover, pretreatment with NO donors, especially SNP, alleviated salt-induced oxidative damage, as indicated by lowered lipid peroxidation, through an enhanced antioxidant system including glutathione accumulation and increased antioxidant enzyme activities. The supply of NO donors is an interesting strategy for alleviating the negative effect of salt on C. paliurus. Our data provide new evidence contributing to the current understanding of NO-induced salt stress tolerance. [ABSTRACT FROM AUTHOR]

Renovascular hypertension is one of the most relevant causes of secondary hypertension, mostly caused by atherosclerotic renovascular stenosis or fibromuscular dysplasia. The increase in angiotensin II production, oxidative stress, and formation of peroxynitrite promotes the decrease in nitric oxide (NO) availability and the development of hypertension, renal and endothelial dysfunction, and cardiac and vascular remodeling. The NO produced by nitric oxide synthases (NOS) acts as a vasodilator; however, endothelial NOS uncoupling (eNOS) also contributes to NO reduced availability in renovascular hypertension. NO donors and NO-derived metabolites have been investigated in experimental renovascular hypertension and have shown promissory effects in attenuating blood pressure and organ damage in this condition. Therefore, understanding the role of decreased NO in the pathophysiology of renovascular hypertension promotes the study and development of NO donors and molecules that can be converted into NO (such as nitrate and nitrite), contributing for the treatment of this condition in the future. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) mediates diverse physiological processes in living organisms. Small molecular NO donors usually lack stability and have a short half‐life in human tissues, limiting the therapeutic application. The anionic tetranitrosyl iron complex with thiosulfate ligands (TNIC) is one of the most promising NO donors. This study shows that bovine serum albumin (BSA) can effectively stabilize the TNIC complex under aerobic (physiological) conditions, which contributes to its prolonged action as NO donor. Our results demonstrated that TNIC-BSA inhibits formation of TBARS – standard biomarker for the lipid peroxidation induced oxidative stress. Also, it was found that TNIC-BSA inhibits the catalytic activity of mitochondrial membrane-bound enzymes: cytochrome c oxidase and monoamine oxidase A. Together, these results demonstrate that, stabilization of TNIC with BSA opens up the possibility of its practical application in chemotherapy of socially significant diseases. • Bovine serum albumin stabilizes the TNIC prolonging its action as NO donor. • TNIC-BSA inhibits formation of TBARS – standard biomarker for the lipid peroxidation. • TNIC-BSA inhibits show inhibition effect on cytochrome c oxidase. • TNIC-BSA inhibits the catalytic activity of monoamine oxidase A [ABSTRACT FROM AUTHOR]

Objective(s): Currently, the development of nanoparticles for the stabilization and targeted delivery of cardiac drugs has gained significance. The present study aimed to develop nontoxic nanoparticles based on chitosan-hyaluronic acid (HA), encapsulate dinitrosyl iron complexes (DNICs, donors NO) into the nanoparticles to increase the stability and effectiveness of their action, and assess the effect of the nanoparticle-DNIC complex on the cell viability of cardiomyocytes.Materials and Methods: Nanoparticles were obtained from chitosan-HA using the ionotropic gelation technology, and the morphology and size of the nanoparticles were determined using electron microscopy. The DNICs were built into the nanoparticles using the physical association method, and the stability of the nanoparticle-DNIC complexes and NO release was investigated using the electrochemical method. Results: Analysis by the electron microscopy showed that the nanoparticles were homogeneous in terms of shape and had an optimal size of ~100 nanometers. In addition, the incorporation of the DNICs into the composition of the nanoparticles significantly increased the stability of the DNICs, while also prolonging the generation of NO and enhancing the yield of nitrogen monoxide. Fluorescence analysis indicated that the chitosan-HA nanoparticles increased the cell viability of rat cardiomyocytes. Conclusion: The nanoparticles were fabricated from chitosan and HA. The encapsulation of the DNICs into the composition of the nanoparticles could stabilize these compounds, while prolonging and increasing the generated nitric oxide. The nanoparticle-DNICs were water-soluble, biocompatible, biodegradable, and nontoxic, which could be used as potential cardiac drugs for the treatment of cardiovascular diseases.

COX-2 can be considered as a clinically relevant molecular target for adjuvant, in particular radiosensitizing treatments. In this regard, using selective COX-2 inhibitors, e.g., in combination with radiotherapy or endoradiotherapy, represents an interesting treatment option. Based on our own findings that nitric oxide (NO)-releasing and celecoxib-derived COX-2 inhibitors (COXIBs) showed promising radiosensitizing effects in vitro, we herein present the development of a series of eight novel NO-COXIBs differing in the peripheral substitution pattern and their chemical and in vitro characterization. COX-1 and COX-2 inhibition potency was found to be comparable to the lead NO-COXIBs, and NO-releasing properties were demonstrated to be mainly influenced by the substituent in 4-position of the pyrazole (Cl vs. H). Introduction of the N-propionamide at the sulfamoyl residue as a potential prodrug strategy lowered lipophilicity markedly and abolished COX inhibition while NO-releasing properties were not markedly influenced. NO-COXIBs were tested in vitro for a combination with single-dose external X-ray irradiation as well as [177Lu]LuCl3 treatment in HIF2α-positive mouse pheochromocytoma (MPC-HIF2a) tumor spheroids. When applied directly before X-ray irradiation or 177Lu treatment, NO-COXIBs showed radioprotective effects, as did celecoxib, which was used as a control. Radiosensitizing effects were observed when applied shortly after X-ray irradiation. Overall, the NO-COXIBs were found to be more radioprotective compared with celecoxib, which does not warrant further preclinical studies with the NO-COXIBs for the treatment of pheochromocytoma. However, evaluation as radioprotective agents for healthy tissues could be considered for the NO-COXIBs developed here, especially when used directly before irradiation.

Cyclocarya paliurus is commonly used to treat diabetes in China. However, the natural habitats of C. paliurus are typically affected by salt stress. Previous studies showed that nitric oxide (NO) level was related to salt tolerance of C. paliurus, and its synthesis was induced by exogenous hydrogen sulfide. However, the effects of different NO donors in alleviating the negative effect of salt stress are still unclear. In the present study, C. paliurus seedlings pretreated with three NO donors (S-nitroso-N-acetylpenicillamine, SNAP and S-nitrosoglutathione, GSNO and sodium nitroprusside, SNP) were exposed to salt stress, and then, the total biomass, chlorophyll fluorescence parameters, NO and glutathione levels, oxidative damage, and antioxidant enzyme activities were investigated. The results showed that pretreatment of NO donors maintained chlorophyll fluorescence and attenuated the loss of plant biomass under salt stress, and the best performance was observed in C. paliurus under SNP treatment. We also found that pretreatment of NO donors further increased the endogenous NO content and nitrate reductase (NR) activity compared with salt treatment. Moreover, pretreatment with NO donors, especially SNP, alleviated salt-induced oxidative damage, as indicated by lowered lipid peroxidation, through an enhanced antioxidant system including glutathione accumulation and increased antioxidant enzyme activities. The supply of NO donors is an interesting strategy for alleviating the negative effect of salt on C. paliurus. Our data provide new evidence contributing to the current understanding of NO-induced salt stress tolerance.

Reactive nitrogen species (RNS), a mediator of nitrosative stress, plays a vital role during wound healing but its role during tissue regeneration is poorly understood. In the present study, the role of RNS was investigated post-tail autotomy and limb amputation in a gecko species, Hemidactylus murrayi Gleadow, 1887. Tail autotomy led to an increased expression of iNOS and nitrosative stress leading to protein S-nitrosylation that probably restricted the acute inflammatory response caused by wounding. Increased nitrosative stress was also associated with proliferation of the wound epithelium and the tail blastema. Nitric oxide synthase inhibitor (L-NAME) caused retarded growth and structural abnormalities in the regenerating tail while peroxynitrite inhibitor (FeTmPyp) arrested tail regeneration. Spermine NONOate and retinoic acid, used as NO donors generated small outgrowths post-amputation of limbs with an increased number of proliferating cells and s-nitrosylation indicating the role of nitric oxide signalling in cell proliferation during regeneration. Additionally, retinoic acid treatment caused regeneration of nerve, muscle and adipose tissue in the regenerated limb structure 105 days post-amputation suggesting it to be a putative modulator of tissue regeneration in the non-regenerating limbs., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite of various therapeutic methods for treating ocular hypertension and glaucoma, it still remains the leading cause of irreversible blindness. Intraocular pressure (IOP) lowering is the most effective way to slow disease progression and prevent blindness. Among the ocular hypotensive drugs currently in use, only a couple act on the conventional outflow system, which is the main pathway for aqueous humor outflow and the major lesion site resulting in ocular hypertension. Nitric oxide (NO) is a commendable new class of glaucoma drugs that acts on the conventional outflow pathway. An increasing number of nitric oxide donors have been developed for glaucoma and ocular hypertension treatment. Here, we will review how NO lowers IOP and the types of nitric oxide donors that have been developed. And a brief analysis of the advantages and challenges associated with the application will be made. The literature used in this review is based on Pubmed database search using ‘nitric oxide’ and ‘glaucoma’ as key words.

Novel both symmetric and asymmetric polyoxymethylene derivatives of bis(oxytriazene N-oxides) were synthesized by the nucleophilic substitution of bis(chloromethyl) ether with salts of oxytriazene N-oxides, their pharmacological properties were preliminary evaluated. [ABSTRACT FROM AUTHOR]

Objective(s): Currently, the development of nanoparticles for the stabilization and targeted delivery of cardiac drugs has gained significance. The present study aimed to develop nontoxic nanoparticles based on chitosanhyaluronic acid (HA), encapsulate dinitrosyl iron complexes (DNICs, donors NO) into the nanoparticles to increase the stability and effectiveness of their action, and assess the effect of the nanoparticle-DNIC complex on the cell viability of cardiomyocytes. Materials and Methods: Nanoparticles were obtained from chitosan-HA using the ionotropic gelation technology, and the morphology and size of the nanoparticles were determined using electron microscopy. The DNICs were built into the nanoparticles using the physical association method, and the stability of the nanoparticle-DNIC complexes and NO release was investigated using the electrochemical method. Results: Analysis by the electron microscopy showed that the nanoparticles were homogeneous in terms of shape and had an optimal size of ~100 nanometers. In addition, the incorporation of the DNICs into the composition of the nanoparticles significantly increased the stability of the DNICs, while also prolonging the generation of NO and enhancing the yield of nitrogen monoxide. Fluorescence analysis indicated that the chitosan-HA nanoparticles increased the cell viability of rat cardiomyocytes. Conclusion: The nanoparticles were fabricated from chitosan and HA. The encapsulation of the DNICs into the composition of the nanoparticles could stabilize these compounds, while prolonging and increasing the generated nitric oxide. The nanoparticle-DNICs were water-soluble, biocompatible, biodegradable, and nontoxic, which could be used as potential cardiac drugs for the treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The reaction of the tetranitrosyl iron complex containing the thiosulfate ligand (TNIC) (NO donor) with phosphoenolpyruvic acid (PEP), which is one of the main biological macroergic compounds, was studied by mass spectrometry. The use of mass spectrometry made it possible to perform studies in an aqueous medium, separate the substances, and quantitatively correlate the peak intensities with the concentrations of the substances. The products of the reaction of PEP with TNIC were identified by IR spectroscopy and mass spectrometry. The reaction product was found to have a Fe–O–C bond. Among the reaction products, the ions with m/z = 318 and 256 belong to the compounds [O3S2–Fe–PEP]–2, and [S-Fe–PEP]–2, respectively. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases include all types of disorders related to the heart or blood vessels. High blood pressure is an important risk factor for cardiac complications and pathological disorders. An increase in circulating angiotensin-II is a potent stimulus for the expression of reactive oxygen species and pro-inflammatory cytokines that activate oxidative stress, perpetuating a deleterious effect in hypertension. Studies demonstrate the capacity of NO to prevent platelet or leukocyte activation and adhesion and inhibition of proliferation, as well as to modulate inflammatory or anti-inflammatory reactions and migration of vascular smooth muscle cells. However, in conditions of low availability of NO, such as during hypertension, these processes are impaired. Currently, there is great interest in the development of compounds capable of releasing NO in a modulated and stable way. Accordingly, compounds containing metal ions coupled to NO are being investigated and are widely recognized as having great relevance in the treatment of different diseases. Therefore, the exogenous administration of NO is an attractive and pharmacological alternative in the study and treatment of hypertension. The present review summarizes the role of nitric oxide in hypertension, focusing on the role of new NO donors, particularly the metal-based drugs and their protagonist activity in vascular function.

Nitric oxide (NO) presents innumerable biological roles, and its exogenous supplementation for therapeutic purposes has become a necessity. Some nanoporous materials proved to be potential vehicles for NO with high storage capacity. However, there is still a lack of information about their efficiency to release controlled NO and if they are biocompatible and biologically stable. In this work, we address this knowledge gap starting by evaluating the NO release and stability under biological conditions and their toxicity with primary keratinocyte cells. Titanosilicates (ETS-4 and ETS-10 types) and clay-based materials were the materials under study, which have shown in previous studies suitable NO gas adsorption/release rates. ETS-4 proved to be the most promising material, combining good biocompatibility at 180 μg/mL, stability and slower NO release. ETS-10 and ETAS-10 showed the best biocompatibility at the same concentration and, in the case of clay-based materials, CoOS is the least toxic of those tested and the one that releases the highest NO amount. The potentiality of these new NO donors to regulate biological functions was assessed next by controlling the mitochondrial respiration and the cell migration. NO-loaded ETS-4 regulates O 2 consumption and cell migration in a dose-dependent manner. For cell migration, a biphasic effect was observed in a narrow range of ETS-4 concentration, with a stimulatory effect becoming inhibitory just by doubling ETS-4 concentration. For the other materials, no effective regulation was achieved, which highlights the relevance of the new assessment presented in this work for nanoporous NO carriers that will pave the way for further developments. Image 1 • Toxicity, stability and NO release assessed for titanosilicates and clays. • First validation of these NO donors to regulate biological functions. • For a positive biological response, low toxicity and slow NO release are required. • ETS-4 proved to regulate cells' O 2 consumption and accelerate cell migration. • Application conditions and effect time window are outlined. [ABSTRACT FROM AUTHOR]

Lung transplantation is an evolutionary procedure from its experimental origin in the twentieth century and is now recognized as an established and routine life-saving intervention for a variety of end-stage pulmonary diseases refractory to medical management. Despite the success and continuous refinement in lung transplantation techniques, the widespread application of this important life-saving intervention is severely hampered by poor allograft quality offered from donors-after-brain-death. This has necessitated the use of lung allografts from donors-after-cardiac-death (DCD) as an additional source to expand the pool of donor lungs. Remarkably, the lung exhibits unique properties that may make it ideally suitable for DCD lung transplantation. However, primary graft dysfunction (PGD), allograft rejection and other post-transplant complications arising from unavoidable ischemia-reperfusion injury (IRI) of transplanted lungs, increase morbidity and mortality of lung transplant recipients annually. In the light of this, nitric oxide (NO), a selective pulmonary vasodilator, has been identified as a suitable agent that attenuates lung IRI and prevents PGD when administered directly to lung donors prior to donor lung procurement, or to recipients during and after transplantation, or administered indirectly by supplementing lung preservation solutions. This review presents a historical account of clinical lung transplantation and discusses the lung as an ideal organ for DCD. Next, the author highlights IRI and its clinical effects in lung transplantation. Finally, the author discusses preservation solutions suitable for lung transplantation, and the protective effects and mechanisms of NO in experimental and clinical lung transplantation. [ABSTRACT FROM AUTHOR]

The asymmetric unit of the title complex, [Pd(C15H13FNO)2], contains one half of the molecule with the PdII cation lying on an inversion centre and is coordinated by the bidentate Schiff base anion. The geometry around the cationic PdII centre is distorted square planar, chelated by the imine N- and phenolate O-donor atoms of the two Schiff base ligands. The N- and O-donor atoms of the two ligands are mutually trans, with Pd—N and Pd—O bond lengths of 2.028 (2) and 1.9770 (18) Å, respectively. The fluorophenyl ring is tilted away from the coordination plane and makes a dihedral angle of 66.2 (2)° with the phenolate ring. In the crystal, molecules are linked into chains along the [101] direction by weak C—H...O hydrogen bonds. Weak π–π interactions with centroid–centroid distances of 4.079 (2) Å stack the molecules along c.

Due to the recognized biological role of nitric oxide (NO) donating derivatives and of selective inhibitors of specific human carbonic anhydrase isoforms (CA, EC 4.2.1.1), promising compounds having an aromatic/heterocyclic primary sulfonamide and functionalized with NO-releasing moieties have been designed. These bifunctional agents have been tested in vitro and in vivo to assess their dual pharmacological activity. According to the encouraging results they could be proposed for the treatment of angle-open glaucoma, cancer regression and osteoporosis, in which both NO and CA activities are involved.

A method for synthesizing new compounds capable of releasing NO within living organisms, namely, 2-azidoethyl derivatives of methylenebis(1-oxytriaz-1-ene 2-oxides) bearing one or few 2-azidoethyl moieties, was developed. The synthesis involves nucleophilic substitution of the bromine atoms of the parent 2-bromoethyl derivatives of methylenebis(1-oxytriaz-1-ene 2-oxides) with the azide group. Some of the synthesized compounds are of interest as promising energetic materials. [ABSTRACT FROM AUTHOR]

Synthesis of new potential NO donors in living organisms, 1,1’-[methylenebis(oxy)]bis(triaz- 1-ene 2-oxides) bearing from two to four 2-nitroxyethyl groups at the nitrogen atoms was accomplished. The developed synthetic approaches involves either nucleophilic substitution of the bromine atoms of the corresponding N-2-bromoethyl derivatives of 1,1’-[methylenebis(oxy)]-bis(triaz-1-ene 2-oxides) or nitration of its 2-hydroxyethyl analogs. Some of the synthesized compounds are of interest as promising energetic materials. [ABSTRACT FROM AUTHOR]

3,3-Bis(2-nitroxyethyl) derivatives of 1,1′-[methylenebis(oxy)]bis(triaz-1-ene 2-oxides) were synthesized by either nucleophilic substitution of the bromine atoms of parent 3,3-bis(2- bromoethyl) compounds or nitration of structurally related 3,3-bis(2-hydroxyethyl) derivatives. The synthesized compounds comprise two different NO donating moieties, namely, oxytriaz- 1-ene 2-oxide and nitrate groups, and, therefore, can be regarded as a new type of NO-donating agents. [ABSTRACT FROM AUTHOR]

Single crystals of new binuclear tetranitrosyl iron complexes ([Fe 2 (SR) 2 (NO) 4 ]) have been synthesized, with R being m-aminophenyl (1) and m-hydroxyphenyl (2). The structure, physical–chemical properties, and NO release of new complexes in comparison with the formerly studied isostructural analog, the complex with R being m-nitrophenyl ligand, were studied by experimental (X-ray, IR, Mössbauer spectroscopy and amperometry) and theoretical (quantum chemical modeling (DFT)) methods. [ABSTRACT FROM AUTHOR]