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Stabilizing nitric oxide: MnFe2O4@Cap-SNO nanoparticles and chitosan hydrogels for controlled therapeutic delivery 稳定一氧化氮:MnFe2O4@Cap-SNO纳米颗粒和壳聚糖水凝胶用于控制治疗递送。
IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-06 DOI: 10.1016/j.niox.2025.10.008
Soodabeh Gharibeh , Melika JaberebnAnsari , Elham Askarizadeh , Azhdar Heydari
Nitric oxide (NO) is a vital bioactive molecule, but its rapid degradation limits therapeutic applications. To enhance stability and controlled release, two novel systems were synthesized: MnFe2O4@Cap-SNO nanoparticles and Cs@Cap-SNO hydrogel. MnFe2O4@Cap-SNO, incorporating captopril (Cap) as an NO donor, demonstrated prolonged NO release for up to 16h upon light exposure, following zero-order kinetics, ensuring sustained delivery. Cs@Cap-SNO, a chitosan-based hydrogel integrating nitrosated captopril (Cap-SNO), exhibited faster NO release governed by Korsmeyer-Peppas kinetics. UV–Vis spectrophotometry confirmed successful nitrosation with distinct absorption bands at 335nm and 545nm. MnFe2O4@Cap-SNO displayed superior stability, outperforming Cs@Cap-SNO and free Cap-SNO in NO preservation. These findings suggest MnFe2O4@Cap-SNO as an effective NO-stabilizing carrier for biomedical applications, particularly intargeted drug delivery. Future studies will focus on in vitro and in vivo validation to assess therapeutic efficacy.
一氧化氮(NO)是一种重要的生物活性分子,但其快速降解限制了其治疗应用。为了提高稳定性和控释,合成了两种新型体系:MnFe2O4@Cap-SNO纳米颗粒和Cs@Cap-SNO水凝胶。MnFe2O4@Cap-SNO,将卡托普利(Cap)作为NO供体,在光照下延长NO释放长达16小时,遵循零级动力学,确保持续递送。Cs@Cap-SNO是一种整合亚硝化卡托普(Cap-SNO)的壳聚糖水凝胶,在Korsmeyer-Peppas动力学的控制下,表现出更快的NO释放。紫外可见分光光度法证实亚硝化成功,在335 nm和545 nm处有不同的吸收带。MnFe2O4@Cap-SNO在NO保存方面表现出较好的稳定性,优于Cs@Cap-SNO和free Cap-SNO。这些发现表明MnFe2O4@Cap-SNO是生物医学应用中有效的no稳定载体,特别是靶向药物递送。未来的研究将集中在体外和体内验证,以评估治疗效果。
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引用次数: 0
Dynamic transformation of the sulfur metabolome during natto fermentation: Supersulfide omics study 纳豆发酵过程中硫代谢组的动态转化:超硫组学研究。
IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-04 DOI: 10.1016/j.niox.2025.11.001
Tomoaki Ida , Shingo Kasamatsu , Mahiro Kuryu , Haruka Nitta , Wakana Nagamura , Hina Yoshida , Ayaka Kinno , Aoi Morishita , Takaaki Akaike , Hideshi Ihara
Supersulfides are sulfur species with catenated sulfur atoms, such as cysteine hydropersulfide (CysSSH). Although supersulfides are biologically important metabolites owing to their unique chemical properties, their transformation in plants via microbial fermentation remains unknown. Natto is a traditional Japanese food prepared from soybeans fermented using Bacillus subtilis var. natto and is an excellent model for investigating this transformation. Compared to unfermented soybeans, natto contains higher supersulfide contents; however, the specific molecular changes that occur during fermentation remain unclear. Herein, we investigated the molecular profiles of supersulfides in natto using mass spectrometry-based supersulfide omics. Quantitative supersulfide profiling revealed an increase in soybean supersulfide content during fermentation using B. subtilis var. natto. However, the total sulfur content did not significantly change, suggesting that microorganisms may play a role in the biotransformation of sulfur-containing molecules into supersulfides. Furthermore, quantitative supersulfide metabolomics and untargeted polysulfide omics revealed time-dependent fermentation increases in the levels of both reduced supersulfides, including CysSSH and cysteine hydrotrisulfide, and oxidized supersulfides, such as cystine trisulfide. Moreover, high-molecular-weight supersulfides were detected. Thus, the supersulfide content significantly increased during B. subtilis var. natto fermentation. Supersulfidated proteins were not detected in natto, likely because soybean-derived proteins were degraded by B. subtilis var. natto. Conversely, supersulfide proteomics revealed the presence of various supersulfide-modified proteins in soybeans, particularly the supersulfidation of 11S glycinin. This is the first study to reveal that microbial fermentation significantly transforms the supersulfide profile in plants. Moreover, the diverse supersulfides abundantly present in natto may contribute to its health-promoting properties.
超硫化物是指硫原子呈链状排列的硫物质,如半胱氨酸氢过硫化物(CysSSH)。虽然由于其独特的化学性质,超硫化物是生物学上重要的代谢物,但它们在植物中通过微生物发酵的转化尚不清楚。纳豆是用枯草芽孢杆菌变种纳豆发酵的大豆制成的传统日本食品,是研究这种转化的一个很好的模型。与未发酵的大豆相比,纳豆含有较高的超硫化物含量;然而,发酵过程中发生的具体分子变化尚不清楚。在此,我们利用基于质谱的超硫化物组学研究了纳豆中超硫化物的分子谱。定量超硫化物分析显示,在纳豆发酵过程中,大豆超硫化物含量增加。但总硫含量变化不明显,提示微生物可能在含硫分子转化为超硫化物的过程中发挥了作用。此外,定量超硫化物代谢组学和非靶向多硫化物组学显示,随着发酵时间的推移,还原超硫化物(包括半胱氨酸氢三硫化物和半胱氨酸氢三硫化物)和氧化超硫化物(如半胱氨酸三硫化物)的水平均有所增加。此外,还检测到高分子量的超硫化物。因此,在纳豆发酵过程中,超硫化物含量显著增加。在纳豆中未检测到超硫化蛋白,可能是因为大豆来源的蛋白被纳豆枯草芽孢杆菌降解。相反,超硫蛋白质组学显示大豆中存在多种超硫修饰蛋白,特别是11S甘氨酸的超硫化。这是第一个揭示微生物发酵显著改变植物中超硫化物的研究。此外,纳豆中丰富的各种超硫化物可能有助于其促进健康的特性。
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引用次数: 0
Involvement of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) levels in precancerous and cancerous cervical lesions 内皮型一氧化氮合酶(eNOS)和一氧化氮(NO)水平在癌前和癌性宫颈病变中的作用
IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-04 DOI: 10.1016/j.niox.2025.11.002
Jaweher Bday , Moufida Souid , Karim H. Farhat , Yosra Macherki , Randa Ghedira , Sallouha Gabbouj , Salwa Shini-Hadhri , Raja Faleh , Elham Hassen
To assess the role of endothelial nitric oxide synthase (eNOS) in cervical cancer, we investigated the association between eNOS −786T/C and intron 4 VNTR 4b/a eNOS gene variations, plasma nitric oxide (NO) levels, cervical lesion occurrence, and disease progression. This study included 78 cervical lesions and 126 healthy controls. Genotyping was performed using polymerase chain reaction (PCR), and plasma NO levels were determined using the Griess reaction. We found that the −786C allele was significantly associated with cervical lesion risk (OR = 2.25; CI 95 % [1.15–4.41]; p = 0.025) and low-grade squamous intraepithelial lesion (L-SIL) risk (OR = 3.22; CI 95 % [1.09–9.686]; p = 0.042) but not with high-grade squamous intraepithelial lesion (H-SIL) and squamous cell carcinoma (SCC). Haplotype analysis showed that the C-4a haplotype was associated with a high risk of cervical lesion development (OR = 2.19, CI 95 % [1.149–4.2]; p = 0.025). Plasma NO levels differed depending on the eNOS variant genotype in cervical lesions and healthy controls. The presence of risk alleles (−786C and/or 4a) correlated with increased plasma NO levels in cervical lesions compared to healthy controls (p = 0.033 and p = 0.039, respectively). As well, the plasma NO levels were higher among cervical lesions than in healthy controls (p = 0.027), mainly among L-SIL (p = 0.004). Moreover, higher plasma NO levels were significantly associated with the presence of human papillomavirus (HPV) DNA among cervical lesions, as well as with a higher HPV circulating viral load. In conclusion, our findings highlight a significant association between eNOS genetic variants, plasma NO levels, and the occurrence and progression of cervical lesions.
为了评估内皮型一氧化氮合酶(eNOS)在宫颈癌中的作用,我们研究了eNOS -786T/C和内含子4 VNTR 4b/a eNOS基因变异、血浆一氧化氮(NO)水平、宫颈病变发生和疾病进展之间的关系。该研究包括78例宫颈病变和126例健康对照。采用聚合酶链反应(PCR)进行基因分型,采用Griess反应测定血浆NO水平。我们发现-786C等位基因与宫颈病变风险(OR=2.25; CI 95% [1.15-4.41]; p= 0.025)和低级别鳞状上皮内病变(L-SIL)风险(OR=3.22; CI 95% [1.09-9.686]; p=0.042)显著相关,但与高级别鳞状上皮内病变(H-SIL)和鳞状细胞癌(SCC)无关。单倍型分析显示,C-4a单倍型与宫颈病变发展的高风险相关(OR= 2.19, CI 95% [1.149-4.2]; p=0.025)。血浆NO水平不同取决于eNOS变异基因型宫颈病变和健康对照。与健康对照组相比,危险等位基因(-786C和/或4a)的存在与宫颈病变血浆NO水平升高相关(分别为p=0.033和p=0.039)。此外,宫颈病变组血浆NO水平高于健康对照组(p=0.027),主要是L-SIL组(p=0.004)。此外,较高的血浆NO水平与宫颈病变中人乳头瘤病毒(HPV) DNA的存在以及较高的HPV循环病毒载量显著相关。总之,我们的研究结果强调了eNOS基因变异、血浆NO水平与宫颈病变的发生和进展之间的显著关联。
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引用次数: 0
Corrigendum to “Cannabidiol induces systemic analgesia through activation of the PI3Kγ/ nNOS/NO/KATP signaling pathway in neuropathic mice. A KATP channel S-nitrosylation-dependent mechanism” [Nitric Oxide 146 (2024) 1–9] 大麻二酚通过激活神经病变小鼠的PI3Kγ/ nNOS/NO/KATP信号通路诱导全身镇痛。KATP通道s -亚硝基化依赖机制[no . 1]。
IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-30 DOI: 10.1016/j.niox.2025.09.004
Douglas Lamounier de Almeida , Renata Cristina Mendes Ferreira , Flávia Cristina Fonseca , Daniel Portela Dias Machado , Danielle Diniz Aguiar , Francisco Silveira Guimaraes , Igor Dimitri Gama Duarte , Thiago Roberto Lima Romero
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引用次数: 0
CYR119, a central nervous system-penetrant stimulator of soluble guanylyl cyclase, improves survival in a mouse model of resuscitation after cardiac arrest CYR119是一种中枢神经系统渗透性刺激剂,可提高心脏骤停后复苏小鼠模型的存活率。
IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-10 DOI: 10.1016/j.niox.2025.10.007
Alexandra Marenco , Yusuke Miyazaki , Melanie Cruz Santos , Takamitsu Ikeda , Eizo Marutani , Paul Lichtenegger , Robert Lukowski , Claire Sinow , Donald B. Bloch , Fumito Ichinose

Background

Treatment with inhaled nitric oxide (NO) improves rates of survival and neurologic outcomes in a mouse model of resuscitation after cardiac arrest. The effect of NO is dependent on the soluble guanylyl cyclase/cyclic guanosine monophosphate (NO-sGC-cGMP) pathway. NO-sGC is a potential target for drugs to modulate NO-dependent signaling in conditions that include ischemia-associated inflammation. The objective of this study was to determine whether CYR119, a stimulator of NO-sGC that can penetrate the central nervous system, improves outcomes after resuscitation from cardiac arrest.

Methods

Adult C57BL/6J wild-type mice of both sexes were subjected to potassium chloride-induced cardiac arrest and cardiopulmonary resuscitation. Fifteen minutes after the return of spontaneous circulation, mice were randomized to receive subcutaneous injections of either CYR119 or vehicle alone. The length of survival after the procedure and degree of neurological dysfunction were assessed. A composite outcome measure was used to define a good outcome as survival with good neurological function, while a poor outcome was defined as either death or exhibiting poor neurologic function. In addition, mRNA levels of inflammatory cytokines in the brain and a plasma marker of kidney injury were measured.

Results

CYR119 significantly improved 10-day survival (35 % in CYR119-treated mice; 15 % in vehicle-treated mice) and the likelihood of achieving a good outcome, demonstrating an association between treatment and both survival and neurological recovery. CYR119-treated mice also exhibited reduced transcript levels of TNF⍺ and IL-1β in the hippocampus and cortex, respectively, and lower plasma creatinine levels.

Conclusion

The current study revealed that CYR119 substantially improved the likelihood of survival with good neurologic function in mice resuscitated from cardiac arrest. The beneficial effects of post-arrest treatment with CYR119 were associated with decreased mRNA expression of inflammatory cytokines in the brain and decreased plasma creatinine levels, suggestive of renal protection. These findings support the potential of CYR119 as a therapeutic strategy for post-cardiac arrest recovery.
背景:在心脏骤停后复苏的小鼠模型中,吸入一氧化氮(NO)治疗可提高生存率和神经系统预后。NO的作用依赖于可溶性鸟苷环化酶/环鸟苷单磷酸(NO- sgc - cgmp)途径。NO-sGC是药物在包括缺血相关炎症在内的条件下调节no依赖信号的潜在靶点。本研究的目的是确定CYR119是否可以改善心脏骤停复苏后的预后,CYR119是一种可以穿透中枢神经系统的NO-sGC刺激剂。方法:采用氯化钾诱导的C57BL/6J野生型成年小鼠进行心脏骤停和心肺复苏。自发循环恢复15分钟后,小鼠被随机分为皮下注射CYR119或单独注射CYR119。评估术后生存时间和神经功能障碍程度。使用复合结果测量将良好结果定义为具有良好神经功能的生存,而不良结果定义为死亡或表现出不良神经功能。此外,还测量了脑内炎症细胞因子mRNA水平和血浆肾损伤标志物。结果:CYR119显著提高了10天生存率(CYR119治疗小鼠为35%,载体治疗小鼠为15%)和获得良好结果的可能性,表明治疗与生存和神经恢复之间存在关联。cyr119处理的小鼠也分别表现出海马和皮质中TNF和IL-1β转录水平降低,血浆肌酐水平降低。结论:目前的研究表明,CYR119显著提高了心脏骤停复苏小鼠存活并具有良好神经功能的可能性。CYR119停搏后治疗的有益效果与脑中炎症细胞因子mRNA表达降低和血浆肌酐水平降低相关,提示肾保护作用。这些发现支持CYR119作为心脏骤停后恢复治疗策略的潜力。
{"title":"CYR119, a central nervous system-penetrant stimulator of soluble guanylyl cyclase, improves survival in a mouse model of resuscitation after cardiac arrest","authors":"Alexandra Marenco ,&nbsp;Yusuke Miyazaki ,&nbsp;Melanie Cruz Santos ,&nbsp;Takamitsu Ikeda ,&nbsp;Eizo Marutani ,&nbsp;Paul Lichtenegger ,&nbsp;Robert Lukowski ,&nbsp;Claire Sinow ,&nbsp;Donald B. Bloch ,&nbsp;Fumito Ichinose","doi":"10.1016/j.niox.2025.10.007","DOIUrl":"10.1016/j.niox.2025.10.007","url":null,"abstract":"<div><h3>Background</h3><div>Treatment with inhaled nitric oxide (NO) improves rates of survival and neurologic outcomes in a mouse model of resuscitation after cardiac arrest. The effect of NO is dependent on the soluble guanylyl cyclase/cyclic guanosine monophosphate (NO-sGC-cGMP) pathway. NO-sGC is a potential target for drugs to modulate NO-dependent signaling in conditions that include ischemia-associated inflammation. The objective of this study was to determine whether CYR119, a stimulator of NO-sGC that can penetrate the central nervous system, improves outcomes after resuscitation from cardiac arrest.</div></div><div><h3>Methods</h3><div>Adult C57BL/6J wild-type mice of both sexes were subjected to potassium chloride-induced cardiac arrest and cardiopulmonary resuscitation. Fifteen minutes after the return of spontaneous circulation, mice were randomized to receive subcutaneous injections of either CYR119 or vehicle alone. The length of survival after the procedure and degree of neurological dysfunction were assessed. A composite outcome measure was used to define a good outcome as survival with good neurological function, while a poor outcome was defined as either death or exhibiting poor neurologic function. In addition, mRNA levels of inflammatory cytokines in the brain and a plasma marker of kidney injury were measured.</div></div><div><h3>Results</h3><div>CYR119 significantly improved 10-day survival (35 % in CYR119-treated mice; 15 % in vehicle-treated mice) and the likelihood of achieving a good outcome, demonstrating an association between treatment and both survival and neurological recovery. CYR119-treated mice also exhibited reduced transcript levels of TNF⍺ and IL-1β in the hippocampus and cortex, respectively, and lower plasma creatinine levels.</div></div><div><h3>Conclusion</h3><div>The current study revealed that CYR119 substantially improved the likelihood of survival with good neurologic function in mice resuscitated from cardiac arrest. The beneficial effects of post-arrest treatment with CYR119 were associated with decreased mRNA expression of inflammatory cytokines in the brain and decreased plasma creatinine levels, suggestive of renal protection. These findings support the potential of CYR119 as a therapeutic strategy for post-cardiac arrest recovery.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 168-175"},"PeriodicalIF":3.2,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unsaturated fatty acids identified as reversible soluble guanylyl cyclase inhibitors 不饱和脂肪酸被鉴定为可逆可溶性鸟酰环化酶抑制剂。
IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-07 DOI: 10.1016/j.niox.2025.10.005
Simon Gissing , Eva-Maria Pferschy-Wenzig , Ramona Jeitler , Michael Russwurm , Astrid Schrammel , Bernd Mayer , Alexander Kollau
As key enzyme in the NO/cGMP pathway, soluble guanylyl cyclase (sGC) has become an important therapeutic target in the treatment of cardiovascular diseases. In addition to activating compounds, inhibitors of sGC are necessary tools in research and may even be desirable as therapeutic agents in certain situations, like migraine.
In a previous study we observed reversible inhibition of isolated sGC by aqueous extracts from tobacco cigarette smoke. In the current study, we found that extracts prepared from cured tobacco share these properties. The active compounds were isolated and identified as unsaturated fatty acids. Further characterization of the inhibitory effect indicated a potential interaction with the heme binding site. In addition, initial experiments with vascular endothelial cells suggest that the observed effect may be relevant to blood vessels function in vivo.
可溶性鸟酰环化酶(sGC)作为NO/cGMP通路的关键酶,已成为心血管疾病治疗的重要靶点。除了激活化合物外,sGC抑制剂是研究中必要的工具,甚至可能在某些情况下作为治疗药物,如偏头痛。在先前的研究中,我们观察到烟草烟雾的水提取物对分离的sGC的可逆抑制作用。在目前的研究中,我们发现从烤烟中提取的提取物具有这些特性。活性化合物经分离鉴定为不饱和脂肪酸。抑制作用的进一步表征表明与血红素结合位点的潜在相互作用。此外,对血管内皮细胞的初步实验表明,所观察到的效果可能与体内血管功能有关。
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引用次数: 0
A versatile vanadium(III)-based chemiluminescence protocol for nitric oxide metabolite quantification and NO release kinetics 基于钒(III)的多功能化学发光方案用于一氧化氮代谢物定量和NO释放动力学。
IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-06 DOI: 10.1016/j.niox.2025.10.006
Joseph A. Bauer , Annette M. Sysel , Michael J. Dunphy
Nitric oxide (NO) is a central mediator of vascular, neurological, and immune functions, and its dysregulation is implicated in a broad spectrum of diseases. Despite its significance, direct measurement of NO in human samples is limited by its transient nature and rapid conversion to nitrate and nitrite. Accurate, rapid, and accessible quantification of these NO metabolites in clinical and research settings remains a key need. We present a vanadium(III)-based chemiluminescence protocol for the reliable detection of nitrate and nitrite in human biological fluids, including serum, urine, and cerebrospinal fluid. In addition, this method supports headspace gas analysis, enabling precise determination of nitric oxide release kinetics and half-life from NO-producing compounds. This approach offers a cost-effective and scalable solution suitable for routine analysis in both diagnostic and research laboratories.
一氧化氮(NO)是血管、神经和免疫功能的中枢介质,其失调与广泛的疾病有关。尽管具有重要意义,但人体样品中NO的直接测量受到其瞬态性质和快速转化为硝酸盐和亚硝酸盐的限制。在临床和研究环境中,准确、快速、方便地量化这些NO代谢物仍然是一个关键需求。我们提出了一种基于钒(III)的化学发光方案,用于可靠地检测人体生物体液(包括血清、尿液和脑脊液)中的硝酸盐和亚硝酸盐。此外,该方法支持顶空气体分析,能够精确测定no生成化合物的一氧化氮释放动力学和半衰期。这种方法提供了一种具有成本效益和可扩展的解决方案,适用于诊断和研究实验室的常规分析。
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引用次数: 0
Roles of nitric oxide in improving post-harvest horticultural product quality: Crosstalk with hydrogen sulfide 一氧化氮在提高收获后园艺产品质量中的作用:与硫化氢的相声。
IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-06 DOI: 10.1016/j.niox.2025.10.004
Yali Qiao , Yayu Liu , Jihua Yu , Weibiao Liao
Postharvest quality maintenance is a key research focus in horticultural science. Nitric oxide (NO), a vital gaseous signaling molecule, significantly improves postharvest quality by inhibiting ethylene (ETH) synthesis, reducing respiration rate, enhancing antioxidant enzyme systems, maintaining cell wall integrity, and regulating secondary metabolism. Currently, the synergistic mechanisms between NO and hydrogen sulfide (H2S) have emerged as a research hotspot. The two molecules work in concert to delay postharvest senescence and enhance fruit resistance to low temperature and pathogens involving enzyme activity regulation and physiological synergy. This review provides a comprehensive analysis of the independent regulatory effects of NO and its crosstalk mechanisms with H2S, providing theoretical foundations for developing efficient and safe postharvest preservation technologies and highlighting their potential applications in green preservation.
摘后品质保持是园艺学研究的热点。一氧化氮(NO)是一种重要的气体信号分子,通过抑制乙烯(ETH)合成、降低呼吸速率、增强抗氧化酶系统、维持细胞壁完整性和调节次生代谢,显著改善采后品质。目前,NO与硫化氢(H2S)的协同作用机制已成为研究热点。这两种分子通过调节酶活性和生理协同作用,共同延缓采后衰老,增强果实对低温和病原菌的抵抗力。本文综述了NO的独立调控作用及其与H2S的串扰机制,为开发高效、安全的采后保鲜技术提供理论依据,并突出其在绿色保鲜中的应用潜力。
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引用次数: 0
Nitric oxide functional relationships with nitrogen-containing stress metabolites: Role in plant adaptation to adverse abiotic factors 一氧化氮与含氮胁迫代谢产物的功能关系:在植物适应不利非生物因子中的作用。
IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-05 DOI: 10.1016/j.niox.2025.10.003
Yuriy E. Kolupaev , Tetiana O. Yastreb , Alla Yemets , Yaroslav Blume
Polyamines, γ-aminobutyric acid (GABA), proline, and glycine betaine (GB) are important plant stress metabolites that are interconnected in common metabolic cycles. These compounds have a multifunctional protective effect on plant cells under stress conditions, acting as osmoregulators, antioxidants, chaperones, and intracellular pH stabilizers, among other roles. The key role of these compounds, however, lies in their involvement in the signaling network of plant cells. Stress metabolites, in particular, engage in a complex functional interaction with reactive oxygen species (ROS) and nitric oxide (NO). Nevertheless, information detailing the links between NO and major nitrogen-containing stress metabolites is fragmented. Consequently, a holistic understanding of these interactions, even at the theoretical model level, has yet to be presented in the literature. The review investigates the phenomenology and mechanisms of NO's involvement as a signaling mediator in the stress-protective function of polyamines and GABA in plants. It also analyses the effect of NO on the content of polyamines, GABA, proline, and GB under normal and stressful conditions. The latest data on the role of S-nitrosation processes of enzymes involved in the regulation of content of low-molecular nitrogen-containing compounds in plant adaptation, and on the effect of polyamines on S-nitrosation of the proteome are summarized. Particular attention is paid to the links between nitric oxide and other signaling mediators (primarily ROS and Ca2+) during its functional interaction with stress metabolites. Regulation of NO and stress metabolite levels is considered one of the promising tools for managing plant stress resistance.
多胺、γ-氨基丁酸(GABA)、脯氨酸和甘氨酸甜菜碱(GB)是重要的植物胁迫代谢产物,它们在共同的代谢循环中相互关联。这些化合物在逆境条件下对植物细胞具有多种保护作用,如渗透调节剂、抗氧化剂、伴侣和细胞内pH稳定剂等。然而,这些化合物的关键作用在于它们参与植物细胞的信号网络。特别是应激代谢产物与活性氧(ROS)和一氧化氮(NO)进行复杂的功能相互作用。然而,详细说明NO和主要含氮应激代谢物之间联系的信息是碎片化的。因此,对这些相互作用的整体理解,即使在理论模型水平上,也尚未在文献中提出。本文就NO作为信号介质参与植物多胺和GABA的胁迫保护功能的现象学及其机制进行了综述。分析了正常和应激条件下NO对多胺、GABA、脯氨酸和GB含量的影响。综述了植物适应过程中参与调节低分子含氮化合物含量的酶的s -亚硝化过程的作用,以及多胺对蛋白质组s -亚硝化作用的最新研究进展。特别关注一氧化氮和其他信号介质(主要是ROS和Ca2+)在其与应激代谢物的功能相互作用中的联系。调控NO和胁迫代谢物水平被认为是调控植物抗逆性的重要手段之一。
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引用次数: 0
Diabetic nephropathy: Role of nitric oxide 糖尿病肾病:一氧化氮的作用。
IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-05 DOI: 10.1016/j.niox.2025.10.001
Sajad Jeddi , Khosrow Kashfi , Asghar Ghasemi
Diabetic nephropathy (DN) is characterized by structural kidney alterations—including glomerular basement membrane thickening, mesangial expansion, tubulointerstitial fibrosis, and glomerular hypertrophy—alongside functional impairments such as reduced glomerular filtration rate (GFR) and albuminuria. DN progresses through five stages: pre-nephropathy, silent, incipient, overt nephropathy, and end-stage kidney disease (ESKD). Dysregulation of the nitric oxide synthase (NOS) pathway—including neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS)—has been increasingly implicated in DN pathogenesis. Evidence from preclinical models using NOS inhibitors and knockout mice, combined with human studies that identify NOS gene polymorphisms, supports this association. In early stages, hyperglycemia elevates GFR, driven by increased NO production from all three NOS isoforms. As the disease progresses, reduced eNOS-derived NO and persistent iNOS overexpression contribute to structural damage and a decline in GFR. NO donors have been shown to prevent early hyperfiltration and attenuate the subsequent decrease in GFR and renal injury characteristic of overt nephropathy. Thus, NO signaling plays a dual role in DN progression and represents a promising target for therapeutic intervention.
糖尿病肾病(DN)的特征是肾脏结构性改变,包括肾小球基底膜增厚、系膜扩张、小管间质纤维化和肾小球肥大,同时伴有肾小球滤过率(GFR)降低和蛋白尿等功能障碍。DN的进展分为五个阶段:肾病前期、无症状、初期、显性肾病和终末期肾病(ESKD)。一氧化氮合酶(NOS)通路的失调-包括神经元NOS (nNOS)、诱导NOS (iNOS)和内皮NOS (eNOS)-越来越多地与DN的发病机制有关。使用NOS抑制剂和敲除小鼠的临床前模型以及鉴定NOS基因多态性的人类研究的证据支持这种关联。在早期阶段,高血糖升高GFR,这是由所有三种NOS异构体产生的NO增加所驱动的。随着疾病进展,enos来源的NO减少和持续的iNOS过表达导致结构损伤和GFR下降。NO供体已被证明可以预防早期的超滤过,并减轻随后GFR的下降和显性肾病的肾损伤特征。因此,NO信号在DN进展中起双重作用,是治疗干预的一个有希望的靶点。
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Nitric oxide : biology and chemistry
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