Nitric oxide : biology and chemistry最新文献_第4页

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

Nitric oxide : biology and chemistry

Pub Date : 2025-12-01 Epub 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。

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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

Nitric oxide : biology and chemistry

Pub Date : 2025-12-01 Epub 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

Nitric oxide based therapies for peripheral artery disease: Evidence and opportunities 基于一氧化氮的外周动脉疾病治疗：证据和机会。

IF 3.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nitric oxide : biology and chemistry

Pub Date : 2025-10-01 Epub Date: 2025-05-16 DOI: 10.1016/j.niox.2025.05.002

Mary M. McDermott , Daniel B. Kim-Shapiro , Jason D. Allen

引用次数: 0

The association between serum and urinary nitric oxide metabolites and fatty liver index: a population-based study 血清和尿一氧化氮代谢物与脂肪肝指数之间的关系：一项基于人群的研究。

IF 3.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nitric oxide : biology and chemistry

Pub Date : 2025-10-01 Epub Date: 2025-05-20 DOI: 10.1016/j.niox.2025.05.004

Zahra Bahadoran , Fereidoun Azizi , Asghar Ghasemi

Background and aim

We investigated the association between fasting serum and urinary nitric oxide metabolite (NOx) levels and fatty liver index (FLI), a non-invasive surrogate of non-alcoholic fatty liver disease (NAFLD) and liver steatosis. Method: This cross-sectional study included 598 adults (aged≥18 years, 48.6 % men) who participated in the Tehran Lipid and Glucose Study (2015–2017). Serum and urine NOx concentrations were quantified using a spectrophotometric method following the Griess reaction. FLI values were calculated using γ-glutamyl transferase, triglycerides, body mass index, and waist circumference. The associations between urinary and serum NOx-to-creatinine (Cr) ratio [either as a categorical variable, i.e., tertiles, or as a continuous variable, i.e., per 1 SD) with NAFLD (i.e., FLI≥60) were assessed using multivariable-adjusted binary logistic regression.

Results

The study participants' mean (SD) age was 42.5 ± 14.6 y. The mean (SD) of serum and urinary NOx was 37.5 ± 16.7 and 1310 ± 751 μmol/L, respectively. The mean (SD) of FLI was 43.3 ± 30.2, and the prevalence of NAFLD was 32.4 %. Serum NOx-to-Cr ratio was not associated with the chance of having NAFLD (OR = 1.66, 95 % CI = 0.98–2.82; P value = 0.058). Higher urinary NOx-to-Cr ratio was significantly associated with a reduced probability of NAFLD (OR = 0.61, 95 % CI = 0.38–0.95, and OR = 0.54, 95 % CI = 0.34–0.87, in the second and third tertiles).

Conclusion

Higher dietary nitrate (NO₃) intake, indicated by increased urinary NOx-to-Cr ratio, is associated with a reduced probability of NAFLD, highlighting the potential role of dietary NO₃ in liver health.

背景和目的：我们研究了空腹血清和尿一氧化氮代谢物（NOx）水平与脂肪肝指数（FLI）之间的关系，FLI是一种非酒精性脂肪性肝病（NAFLD）和肝脏脂肪变性的无创替代指标。方法：本横断面研究纳入了参加德黑兰脂质和葡萄糖研究（2015-2017）的598名成年人（年龄≥18岁，48.6%为男性）。在Griess反应后，用分光光度法定量测定血清和尿液NOx浓度。使用γ-谷氨酰转移酶、甘油三酯、体重指数和腰围计算FLI值。尿和血清nox -肌酐（Cr）比值[作为一个分类变量，即分位数，或作为一个连续变量，即每1 SD)与NAFLD（即FLI≥60）之间的关系使用多变量调整的二元逻辑回归进行评估。结果：研究对象的平均（SD）年龄为42.5±14.6岁，血清和尿液NOx的平均（SD）分别为37.5±16.7和1310±751 μmol/L。FLI的平均值（SD）为43.3±30.2，NAFLD患病率为32.4%。血清nox - cr比值与NAFLD发生率无相关性(OR=1.66, 95% CI=0.98-2.82；P值= 0.058)。较高的尿nox - cr比值与NAFLD发生率降低显著相关（OR=0.61, 95% CI=0.38-0.95， OR=0.54, 95% CI=0.34-0.87，在第二和第三分位）。结论：较高的膳食硝酸盐（NO3）摄入量（表现为尿nox / cr比值增加）与NAFLD的可能性降低相关，突出了膳食NO3在肝脏健康中的潜在作用。

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引用次数: 0

Biomechanical study on the effect of changes in ostiomeatal complex structure on NO concentration in the nasal cavity 口鼻道复合体结构变化对鼻腔NO浓度影响的生物力学研究

IF 3.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nitric oxide : biology and chemistry

Pub Date : 2025-10-01 Epub Date: 2025-06-04 DOI: 10.1016/j.niox.2025.06.001

Shen Yu , Xiaojun Xie , Danqing Wang , Yan Guo , Jizhe Wang

Background

Nitric oxide (NO) concentration in the nasal cavity plays an important role in maintaining nasal function and health. We investigated the influence of the geometric structure of the ostiomeatal complex (OMC) on nasal cavity NO concentration distribution and provide optimization strategies for reconstruction surgery related to OMC function.

Method

ology: Numerical nasal cavity models of 21 healthy volunteers were established, and the effects of the OMC structure on NO distribution in the nasal cavity were numerically studied. Additionally, the nasal meatus widths of five healthy adult New Zealand rabbits were modified surgically. Exhaled NO concentration was measured pre- and post-surgery to study the effect of nasal meatus width on NO distribution in the rabbit nasal cavities.

Results

Through numerical analysis, a quantified relationship was obtained between the width of the middle nasal passage, the hydraulic diameter of the maxillary sinus ostium, and airflow rate with the concentration of NO in the nasal and paranasal sinuses. The impact of these three factors on the NO concentration of exhaled airflow was compared across all volunteers. An optimal combination of middle nasal passage width and ostium diameter can ensure a normal NO concentration in the nasal cavity.

Conclusions

When reconstructing the OMC structure to restore function, factors such as the width of the middle nasal meatus and maxillary sinus ostium area and length should be considered comprehensively to reshape an optimal OMC structure for achieving a normal physiological distribution of NO concentration in the nasal cavity.

鼻腔内一氧化氮（NO）浓度在维持鼻腔功能和健康中起着重要作用。我们研究了口鼻道复合体（OMC）的几何结构对鼻腔NO浓度分布的影响，并为OMC功能相关的重建手术提供优化策略。方法：建立21例健康志愿者鼻腔数值模型，数值研究OMC结构对鼻腔NO分布的影响。另外，对5只健康成年新西兰兔的鼻道宽度进行了手术修饰。术前、术后测定兔呼出一氧化氮浓度，研究鼻道宽度对兔鼻腔内一氧化氮分布的影响。结果通过数值分析，得到了鼻中通道宽度、上颌窦口水力直径、气流速率与鼻、鼻窦NO浓度之间的定量关系。比较了这三个因素对所有志愿者呼出气流中NO浓度的影响。鼻中通道宽度和鼻孔直径的最佳组合可以保证鼻腔内正常的NO浓度。结论在重建OMC结构以恢复功能时，应综合考虑鼻中道宽度和上颌窦口面积、长度等因素，重塑最佳的OMC结构，使鼻腔内NO浓度达到正常的生理分布。

{"title":"Biomechanical study on the effect of changes in ostiomeatal complex structure on NO concentration in the nasal cavity","authors":"Shen Yu , Xiaojun Xie , Danqing Wang , Yan Guo , Jizhe Wang","doi":"10.1016/j.niox.2025.06.001","DOIUrl":"10.1016/j.niox.2025.06.001","url":null,"abstract":"<div><h3>Background</h3><div>Nitric oxide (NO) concentration in the nasal cavity plays an important role in maintaining nasal function and health. We investigated the influence of the geometric structure of the ostiomeatal complex (OMC) on nasal cavity NO concentration distribution and provide optimization strategies for reconstruction surgery related to OMC function.</div></div><div><h3>Method</h3><div>ology: Numerical nasal cavity models of 21 healthy volunteers were established, and the effects of the OMC structure on NO distribution in the nasal cavity were numerically studied. Additionally, the nasal meatus widths of five healthy adult New Zealand rabbits were modified surgically. Exhaled NO concentration was measured pre- and post-surgery to study the effect of nasal meatus width on NO distribution in the rabbit nasal cavities.</div></div><div><h3>Results</h3><div>Through numerical analysis, a quantified relationship was obtained between the width of the middle nasal passage, the hydraulic diameter of the maxillary sinus ostium, and airflow rate with the concentration of NO in the nasal and paranasal sinuses. The impact of these three factors on the NO concentration of exhaled airflow was compared across all volunteers. An optimal combination of middle nasal passage width and ostium diameter can ensure a normal NO concentration in the nasal cavity.</div></div><div><h3>Conclusions</h3><div>When reconstructing the OMC structure to restore function, factors such as the width of the middle nasal meatus and maxillary sinus ostium area and length should be considered comprehensively to reshape an optimal OMC structure for achieving a normal physiological distribution of NO concentration in the nasal cavity.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 38-44"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230592","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

Antagonistic effect of a nitric oxide donor agents based on ruthenium complex combined with cisplatin on lung tumor cell lines 钌络合物联合顺铂的一氧化氮供体对肺肿瘤细胞系的拮抗作用。

IF 3.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nitric oxide : biology and chemistry

Pub Date : 2025-10-01 Epub Date: 2025-05-31 DOI: 10.1016/j.niox.2025.05.009

Angelica E. Graminha , Amanda B. Becceneri , Rafaella R Rios , Márcia Regina Cominetti , Juliana Cristina Biazzotto , Roberto Santana da Silva

Nitric oxide (NO) is a versatile biological messenger involved in numerous physiological processes and anticancer mechanisms. Its functions are highly dependent on its concentration and the specific site of action. In this study, we investigated the effects of controlled NO release mediated by ruthenium-based compounds. The tests demonstrated the significant potential of combining cisplatin with the non-cytotoxic ruthenium nitrosyl complexes cis-[Ru(bpy)₂(NO₂)(solv)]PF₆ and cis-Ru(bpy)₂(NO)(pic)](PF₆)₃, where bpy = 2,2′-bipyridine ,pic = 4-picoline and solv = solvent. This combination increased selectivity between non-tumoral and tumoral lung cells (MRC-5/A549) compared to the selectivity index of cisplatin alone. These nitrosyl complexes exhibited an antagonistic interaction with cisplatin, reducing its cytotoxic efficacy. Cell cycle and apoptosis assays revealed that the cisplatin/Ru combination more effectively inhibited cisplatin's cytotoxic effect on the MRC-5 non-tumoral lung cell line compared to the A549 tumoral cell line. Morphological assays conducted in 3D culture with the cis-[Ru(bpy)₂(NO)(pic)](PF₆)₃ complex confirmed its chemopreventive behavior, as the 3D system closely mimics in vivo conditions. Moreover, the absence of cytotoxicity in these ruthenium nitrosyl complexes highlights their potential as promising candidates for adjuvant therapy in combination with other drugs.

一氧化氮（NO）是一种多用途的生物信使，参与许多生理过程和抗癌机制。它的功能高度依赖于它的浓度和特定的作用部位。在这项研究中，我们研究了钌基化合物介导的控制NO释放的影响。试验表明，顺铂与无细胞毒性的钌亚硝基配合物顺式-[Ru(bpy)2(NO2)(solv)]PF6和顺式-Ru(bpy)2(NO)(pic)](PF6)3结合具有显著的潜力，其中bpy = 2,2'-联吡啶，pic = 4-吡啶（顺铂/Ru）。与单用顺铂的选择性指数相比，联合用药增加了非肿瘤和肿瘤肺细胞（MRC-5/A549）之间的选择性。这些亚硝基复合物表现出与顺铂的拮抗相互作用，降低其细胞毒性作用。细胞周期和凋亡实验显示，与A549肿瘤细胞系相比，顺铂/Ru联合治疗更有效地抑制顺铂对MRC-5非肿瘤肺细胞系的细胞毒作用。用顺式-[Ru(bpy)2(NO)(pic)](PF6)3配合物在三维培养中进行的形态学分析证实了其化学预防作用，因为三维系统非常接近体内条件。此外，这些钌亚硝基络合物没有细胞毒性，突出了它们作为与其他药物联合辅助治疗的有希望的候选者的潜力。

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引用次数: 0

The Nitric Oxide Society and the Nitric Oxide Journal: Returning to our foundation to shape the future of redox biology 一氧化氮学会和一氧化氮杂志：回到我们的基础，塑造氧化还原生物学的未来。

IF 3.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nitric oxide : biology and chemistry

Pub Date : 2025-10-01 Epub Date: 2025-05-21 DOI: 10.1016/j.niox.2025.05.005

Miriam M. Cortese-Krott , Lorenzo Berra , Nathan S. Bryan , Mattias Carlström , Sharon Glynn , Adrian Hobbs , Katrina M. Miranda , Hozumi Motohashi , Motohiro Nishida , Ciara E. O'Neill , Jesus Tejero

The Nitric Oxide Society and its journal, Nitric Oxide: Biology and Chemistry, are renewing their partnership to reconnect with their founding mission—supporting a dynamic, global redox community. Established together in 1996, the Society and Journal now return to a shared path, aligning efforts to empower young scientists, promote rigorous publishing, and foster open, international collaboration. As nitric oxide and related species move to the forefront of biomedical research and personalized medicine, this relaunch is less a restart than a return to form—focused, inclusive, and forward-looking.

一氧化氮学会和它的期刊《一氧化氮：生物学和化学》正在更新他们的伙伴关系，以重新连接他们的创始使命——支持一个充满活力的全球氧化还原社区。该学会和《期刊》于1996年共同成立，现在回到了共同的道路上，共同努力赋予年轻科学家权力，促进严谨的出版，促进开放的国际合作。随着一氧化氮和相关物种走向生物医学研究和个性化医疗的前沿，这次重新启动与其说是重新开始，不如说是回归到以形式为中心、包容和前瞻性。

引用次数: 0

Corrigendum to “Catestatin alleviates PASMC phenotypic switching-mediated pulmonary arterial remodeling in a rat model of MCT-induced pulmonary arterial hypertension by promoting endothelium-derived NO synthesis” [Nitric Oxide158 (2025) 93–105] “Catestatin通过促进内皮源性NO合成减轻mct诱导的肺动脉高压大鼠模型中PASMC表型转换介导的肺动脉重塑”的更正[NO， 158(2025) 93-105]。

IF 3.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nitric oxide : biology and chemistry

Pub Date : 2025-10-01 Epub Date: 2025-08-21 DOI: 10.1016/j.niox.2025.08.002

Zheyu Liu , Bo Cui , Hao Ju , Tuantuan Tan , Jinchun Wu , Manqi Yang , Saeed Kashkooli , Mian Cheng , Gang Wu , Tao Liu

引用次数: 0

Impact of low nitrate/nitrite diet and nitrate supplementation on litter size and fetal and placental growth in pregnant mice 低硝酸盐/亚硝酸盐饲粮和添加硝酸盐对产仔数和胎胎盘生长的影响

IF 3.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nitric oxide : biology and chemistry

Pub Date : 2025-10-01 Epub Date: 2025-06-06 DOI: 10.1016/j.niox.2025.06.002

Hager M. Kowash , Teresa Tropea , Mark R. Dilworth , Jon O. Lundberg , Eddie Weitzberg , Carina Nihlen , Elizabeth C. Cottrell

Background

In pregnancy, nitric oxide (NO) plays important roles in embryo development, maternal cardiovascular function, fetoplacental blood flow and fetal growth. Whilst the importance of NO synthase (NOS)-derived NO has been studied in pregnancy, evidence for the role of NO derived from dietary nitrate is lacking. Herein, we utilised dietary manipulation strategies to investigate the effects of dietary nitrate depletion/supplementation on pregnancy outcomes in mice.

Methods

Pregnant dams received either a standard control diet or a commercially available nitrate/nitrite depleted (low NOx) diet from the start of pregnancy, along with drinking water containing either 0.7 mM NaNO₃ or 0.7 mM NaCl as control. Pregnancy outcomes (litter size, fetal/placental weights) and maternal and fetal plasma nitrate/nitrite concentrations were determined at gestational day 17.5.

Results and discussion

Litter size was unaffected by maternal low NOx diet, but fetal and placental weights were significantly reduced (p < 0.001 for both). Maternal plasma nitrate and nitrite concentrations were significantly lower in low NOx animals (p = 0.017 and p = 0.003, respectively), with maternal 0.7 mM NaNO₃ supplementation restoring nitrate, but not nitrite, levels. Whilst fetal and placental weights were unaffected by maternal NaNO₃ supplementation, litter size was significantly increased (p = 0.024). Unexpectedly, maternal food/energy intake was significantly reduced in low NOx dams (p < 0.001), suggesting that the lower fetal and placental weights may be due to nutrient insufficiency, rather than nitrate depletion per se. These findings have important implications for the interpretation of studies using commercial low NOx diets to study the effects of nitrate-depletion, particularly where food intake has not been previously reported.

在妊娠期，一氧化氮（NO）在胚胎发育、母体心血管功能、胎胎盘血流和胎儿生长中起着重要作用。虽然已经研究了NO合成酶（NOS）衍生的NO在妊娠中的重要性，但缺乏从膳食硝酸盐中衍生的NO的作用的证据。在此，我们利用饮食操纵策略来研究饮食中硝酸盐的消耗/补充对小鼠妊娠结局的影响。方法妊娠母鼠在妊娠初期分别饲喂标准对照日粮或市售的低NOx（硝酸盐/亚硝酸盐）日粮，同时饮用含有0.7 mM NaNO3或0.7 mM NaCl的饮用水作为对照。在妊娠第17.5天测定妊娠结局（产仔数、胎儿/胎盘重量）以及母体和胎儿血浆硝酸盐/亚硝酸盐浓度。低氮氧化物饲粮对产仔数无影响，但显著降低了胎重和胎盘重(p <；两者均为0.001)。低氮氧化物动物的母体血浆硝酸盐和亚硝酸盐浓度显著降低（分别为p = 0.017和p = 0.003），母体添加0.7 mM NaNO3可恢复硝酸盐水平，但不能恢复亚硝酸盐水平。虽然母体添加NaNO3对胎儿和胎盘重量没有影响，但产仔数显著增加（p = 0.024）。出乎意料的是，低氮氧化物母鼠的食物/能量摄入量显著降低(p <；0.001)，表明较低的胎儿和胎盘重量可能是由于营养不足，而不是硝酸盐本身的消耗。这些发现对于解释使用商业低氮氧化物饮食研究硝酸盐消耗影响的研究具有重要意义，特别是在以前未报告食物摄入的情况下。

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引用次数: 0

Nitric oxide tuning enhances cytotoxicity and reduces inflammation in prostate cancer nanotherapy. 一氧化氮调节增强细胞毒性并减少前列腺癌纳米治疗中的炎症。

IF 3.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nitric oxide : biology and chemistry

Pub Date : 2025-10-01 Epub Date: 2025-08-05 DOI: 10.1016/j.niox.2025.08.001

Joana Claudio Pieretti, Giovana Marchini Armentano, Marcela Sorelli Carneiro-Ramos, Amedea Barozzi Seabra

Modulating intracellular nitric oxide (NO) levels offers a promising strategy to enhance tumor cell sensitivity to nanoparticle-based therapies. In this study, we investigated the impact of intracellular NO modulation in prostate cancer cells (PC3) using S-nitrosoglutathione (GSNO, a NO donor) and L-nitro arginine methyl ester (l-NAME, a nitric oxide synthase (NOS) inhibitor), in combination with cisplatin-loaded zinc oxide nanoparticles (ZnO/CisPt NPs). These nanoparticles, previously shown to exert selective cytotoxicity against PC3 cells, had their therapeutic performance further enhanced by NO modulation, which led to reduced NOS expression and regulation of inflammatory cytokines. Interestingly, both the increase and the depletion of intracellular S-NO levels contributed to tumor cell sensitization to the nanoparticle-based treatment. These results indicate that altering NO balance, regardless of direction, plays a key role in how cells respond to therapy. Our results reinforce the relevance of NO signaling in augmenting the efficacy of nanomedicine approaches while minimizing tumor-associated inflammation, offering a safer and more targeted strategy for prostate cancer treatment with potential for broader applications in oncology.

调节细胞内一氧化氮（NO）水平为提高肿瘤细胞对纳米颗粒治疗的敏感性提供了一种有希望的策略。在这项研究中，我们研究了s -亚硝基谷胱甘肽（GSNO， NO供体）和l -硝基精氨酸甲酯（L-NAME，一氧化氮合酶（NOS）抑制剂）联合顺铂负载氧化锌纳米颗粒（ZnO/CisPt NPs）对前列腺癌细胞（PC3）细胞内NO调节的影响。这些纳米颗粒先前被证明对PC3细胞具有选择性细胞毒性，通过NO调节，其治疗性能进一步增强，导致NOS表达减少和炎症细胞因子的调节。有趣的是，细胞内S-NO水平的增加和减少都有助于肿瘤细胞对纳米颗粒治疗的敏化。这些结果表明，改变NO平衡，无论方向如何，在细胞对治疗的反应中起着关键作用。我们的研究结果强化了NO信号在增强纳米医学方法疗效的同时最小化肿瘤相关炎症的相关性，为前列腺癌治疗提供了一种更安全、更有针对性的策略，在肿瘤学领域具有更广泛的应用潜力。

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引用次数: 0