Nitric oxide : biology and chemistry最新文献

Objective

Hydrogen sulfide (H₂S) is associated with depressive-like behavior in rodents. We undertook cross-sectional and longitudinal analyses of plasma levels of H₂S and its substrate homocysteine (Hcy) in depression and assessed the association of both parameters with psychopathology and cognitive function.

Methods

Forty-one patients suffering from depression (PSDs) and 48 healthy volunteers were recruited. PSDs were treated for 8 weeks. Analyzable data were collected from all participants for assessment of their psychopathology and cognitive function. Plasma was collected for determination of levels of H₂S and Hcy, and data were correlated to determine their potential as plasma biomarkers.

Results

Cross-sectional analyses revealed PSDs to have a low plasma H₂S level and high Hcy level. Longitudinal analyses revealed that 8 weeks of treatment reversed the changes in plasma levels of H₂S and Hcy in PSDs. Plasma levels of H₂S and Hcy were associated with psychopathology and cognitive function in depression. The area under the receiver operating characteristic curve (AUC) for a combination of plasma levels of H₂S and Hcy and expression of the TNF gene (i.e., H₂S–Hcy–TNF) was 0.848 for diagnosing depression and 0.977 for predicting the efficacy of antidepressant agents.

Conclusion

Plasma levels of H₂S and Hcy reflect changes in psychopathology and cognitive function in depression and H₂S–Hcy–TNF has the potential to diagnose depression and predict the efficacy of antidepressant medications.

The precise release and characterization of nitroxyl (HNO) gas signaling molecule remain a challenge due to its short lifetime to date. To solve this issue, an azobenzene-based HNO donor (Azo-D1) was proposed as a colorimetric and fluorometric chemosensor for HNO releasing, to release both HNO and an azobenzene fluorescent reporter together. Specifically, the Azo-D1 has an HNO release half-life of ∼68 min under physiological conditions. The characteristic color change from the original orange to the yellow color indicated the decomposition of the donor molecule. In addition, the stoichiometry release of HNO was qualitatively and quantitatively verified through the classical phosphine compound trap. As compared with the donor molecule by itself, the decomposed product demonstrates a maximum fluorescence emission at 424 nm, where the increase of fluorescence intensity by 6.8 times can be applied to infer the real-time concentration of HNO. Moreover, cellular imaging can also be achieved using this Azo-D1 HNO donor through photoexcitation at 405 and 488 nm, where the real-time monitoring of HNO release was achieved without consuming the HNO source. Finally, the Azo-D1 HNO donor would open a new platform in the exploration of the biochemistry and the biology of HNO.

Hydrogen sulfide (H₂S) is the third new gas signaling molecule in the human body after the discovery of NO and CO. Similar to NO, it has the functions of vasodilation, anti-inflammatory, antioxidant, and regulation of cell formation. Enzymes that can produce endogenous H₂S, such as CSE, CSB, and 3-MST, are common in liver tissues and are important regulatory molecules in the liver. In the development of liver fibrosis, H₂S concentration and expression of related enzymes change significantly, which makes it possible to use exogenous gases to treat liver diseases. This review summarizes the role of H₂S in liver fibrosis and its complications induced by NAFLD and CCl₄, and elaborates on the anti-liver fibrosis effect of H₂S through the mechanism of reducing oxidative stress, inhibiting inflammation, regulating autophagy, regulating glucose and lipid metabolism, providing theoretical reference for further research on the treatment of liver fibrosis with H₂S.

Background

Multiple sclerosis (MS) is a chronic and immune-mediated disease of unknown etiology and leading to a physical and cognitive disability. Different studies suggest that nitrosative stress may play a pivotal role in the pathogenesis and disability in MS. Besides, reports evaluated NO and their metabolites, expressed by nitrite and nitrate (NOx) levels of MS patients compared with other pathologies, but did not evaluate disability and relapse/remission phases.

Objective

Thus, this study aimed to conduct a systematic review and meta-analysis of NOx levels in MS patients in relapse/remission phases and its involvement in patient disability.

Methods

The protocol was registered in PROSPERO (CRD42022327161). We used GRADE to estimate the articles' quality and evaluated the publication bias using Egger's and Begg's tests.

Results

Here, through a search in the Pubmed, Scopus, and EMBASE databases, 5.276 studies were found, and after the selection process, 20 studies were included in this systematic review and meta-analysis. The studies included data from 1.474 MS patients and 1.717 healthy controls, 1.010 RRMS and 221 primary progressive MS (PPMS).

Conclusion

NOx levels are increased in relapsing-remitting MS (RRMS) patients in the relapse phase. Also, NOx levels were increased in MS patients with higher disability. However, further studies are still needed to control lifestyle habits, pain, and MS treatment effects in biased NOx levels.

Nitric oxide (NO), a vasodilator contributes to the vaso-occlusive crisis associated with the sickle cell disease (SCD). Vascular nitric oxide helps in vasodilation, controlled platelet aggregation, and preventing adhesion of sickled red blood cells to the endothelium. It decreases the expression of pro-inflammatory genes responsible for atherogenesis associated with SCD. Haemolysis and activated endothelium in SCD patients reduce the bioavailability of NO which promotes the severity of sickle cell disease mainly causes vaso-occlusive crises. Additionally, NO depletion can also contribute to the formation of thrombus, which can cause serious complications such as stroke, pulmonary embolism etc. Understanding the multifaceted role of NO provides valuable insights into its therapeutic potential for managing SCD and preventing associated complications. Various clinical trials and studies suggested the importance of artificially induced nitric oxide and its supplements in the reduction of severity. Further research on the mechanisms of NO depletion in SCD is needed to develop more effective treatment strategies and improve the management of this debilitating disease.

Nitric oxide (NO), as a vital cellular signalling molecule in physiological processes, has been found to play an important role in various biological functions. In this study, we rationally designed three NO donors by tethering nitrobenzene derivatives to three fluorescent chromophores. NX-NO was found to release NO and exhibit a high fluorescence turn-on signal ratio upon exposure to LED yellow light. Additionally, it had excellent photo-stability and good inhibitory activity against cancer cell proliferation, and was successfully applied to cell imaging. Moreover, we detected the release of NO and fluorescence response in the blood of a mouse, suggesting its potential therapeutic application in living organisms.

Heart failure (HF) is a multifactorial, heterogeneous systemic disease that is considered one of the leading causes of death and morbidity worldwide. It is well-known that endothelial dysfunction (ED) plays an important role in cardiac disease etiology. A reduction in the bioavailability of nitric oxide (NO) in the bloodstream leads to vasoconstriction and ED. Many studies indicated diminishment of peripheral arteries vasodilation that is mediated by the endothelium in the of patients with chronic HF. With the advancement of nanomedicine, nanotechnology can provide adequate solutions for delivering exogenous NO with the aid of nanoparticles (NPs) to treat ED. The properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable both passive and active delivery of drugs. This prompted us to investigate the efficacy of our newly-developed hydrogel nanoparticles (NO-RPs) for the delivery and sustained release of NO gas to alleviate cardiac failure and inflammation in the heart failure zebrafish model. The hydrogel NO-RPs incorporate SPIONS and NO precursor. The sustainend release of NO in the NO-RPs (4200 s), overcomes the problem of the short half life of NO in vivo which is expected to ameliorate the reduced NO bioavailabilty, and its consequences in endothelial and cardiac dysfunction. Zebrafish embryos were used as the animal model in this study to determine the effect of SPIONs-loaded NO-RPs on the cardiovascular system. Cardiac failure was induced in 24hpf embryos by exposure to aristolochic acid (AA)(0.25, 0.5 μM) for 8 h, followed by the SPIONs-loaded NO-RPs (0.25, 0.5 mg/ml) for 48 h, experimental groups included: control group which is healthy non treated zebrafish embryos, AA injured zebrafish embryos (HF) model,and NO-RP treated HF zebrafish embryos. Survival rate was assessed at 72hpf. Cardiac function was also evaluated by analyzing cardiac parameters including heartbeat, major blood vessels primordial cardinal vein and dorsal aorta (PCV &DA) diameter, blood flow velocity in PCV & DA vessels, cardiac output, and PCV & DA shear stresses. All cardiac parameters were analyzed with the aid of MicroZebraLab blood flow analysis software from Viewpoint. In addition, we studied the molecular effects of the developed NO-RPs on the mRNA expression of selected pro-inflammatory markers: IL-6, and Cox-2. Our findings demonstrated that the NO-RPs improved the survival rate in the heart failure zebrafish model and reversed heart failure by enhancing blood flow perfusion in Zebrafish embryos, significantly. In addition, RT-PCR results showed that the NO-RPs significantly reduced the expression of pro-inflammatory markers (lL-6&COX-2) in the heart failure zebrafish model. Our study confirmed that the developed SPIONs-loaded NO-RPs are effective tool to alleviate cardiac failure and inflammation in the HF zebrafish model.

This review aims to analyze the developmental trajectory of hydrogen sulfide (H2S) donors over the past three decades and explore the historical background, research hotspots, and emerging trends in related fields from a temporal perspective. A total of 5092 literature articles on H2S donors were retrieved from the Web of Science Core Collection (WoSCC), encompassing 1303 journals, 20638 authors, 10992 institutions, and 459 countries and regions. Utilizing CiteSpace as a bibliometric tool, historical features, evolving active topics, and emerging trends in the field of H2S donors were identified. Over the past 30 years, the field of H2S donors has remained in a prominent stage. This article discusses both inorganic and organic types of H2S donors, including NaHS and Na2S, GYY4137, AP39, and AP123, as well as briefly outlines research and applications of H2S donors in nanotechnology, advanced materials, composite materials, nanostructures, and optical properties. Mechanistically, the review outlines how H2S donors regulate cellular signal transduction, anti-inflammatory responses, neuroprotection, and other pathways within the organism by modulating protein S-sulfhydration, antioxidant effects, and interactions with metal proteins. In terms of applications, the review summarizes the extensive use of H2S donors in biomedical research, encompassing cardiovascular, neurological, anti-inflammatory, and anti-cancer characteristics, as well as their potential applications in the treatment of metabolic diseases. Finally, challenges and limitations faced by H2S donor research are discussed, and potential future research directions are proposed.

Hydrogen sulfide (H₂S), traditionally recognized as a noxious gas with a pungent odor, has emerged as a fascinating metabolite originating from proteinaceous foods. This review provides a comprehensive examination of H₂S regulatory metabolism in cell. Dysregulation of cellular processes plays a pivotal role in the pathogenesis of numerous diseases. Recent development explores the chemistry of biosynthesis and degradation of H₂S in cells. The consequences of dysregulation causing diseases and the emerging role of hydrogen sulfide (H₂S) modulation as a promising therapeutic platform has not been explored much. These disturbances can manifest as oxidative stress, inflammation, and aberrant cellular signaling pathways, contributing to the development and progression of diseases such as cancer, cardiovascular disorders, neurodegenerative diseases, and diabetes. Hydrogen sulfide has gained recognition as a key player in cellular regulation. H₂S is involved in numerous physiological processes, including vasodilation, inflammation control, and cytoprotection. Recent advances in research have focused on modulating H₂S levels to restore cellular balance and mitigate disease progression. This approach involves both exogenous H₂S donors and inhibitors of H₂S -producing enzymes. By harnessing the versatile properties of H₂S, researchers and clinicians may develop innovative therapies that address the root causes of dysregulation-induced diseases. As our understanding of H₂S biology deepens, the potential for precision medicine approaches tailored to specific diseases becomes increasingly exciting, holding the promise of improved patient outcomes and a new era in therapeutics.

In the face of escalating salinity stress challenges in agricultural systems, this review article delves into the harmonious partnership between hydrogen sulfide (H₂S) and nitric oxide (NO) as they collectively act as formidable defenders of plants. Once considered as harmful pollutants, H₂S and NO have emerged as pivotal gaseous signal molecules that profoundly influence various facets of plant life. Their roles span from enhancing seed germination to promoting overall growth and development. Moreover, these molecules play a crucial role in bolstering stress tolerance mechanisms and maintaining essential plant homeostasis. This review navigates through the intricate signaling pathways associated with H₂S and NO, elucidating their synergistic effects in combating salinity stress. We explore their potential to enhance crop productivity, thereby ensuring food security in saline-affected regions. In an era marked by pressing environmental challenges, the manipulation of H₂S and NO presents promising avenues for sustainable agriculture, offering a beacon of hope for the future of global food production.