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A Multimodal Omics Exploration of the Motor and Non-Motor Symptoms of Parkinson’s Disease 帕金森病运动和非运动症状的多模态组学研究
Pub Date : 2022-03-08 DOI: 10.3390/ijtm2010009
F. Lejeune, F. Ichou, Etienne Camenen, B. Colsch, Florence Mauger, C. Peltier, I. Moszer, Emmanuel Gilson, Morgane Pierre-Jean, Edith Le Floch, Victor Sabarly, A. Tenenhaus, J. Deleuze, C. Ewenczyk, M. Vidailhet, F. Mochel
Parkinson’s disease (PD) is the second most common neurodegenerative disease clinically characterized by classical motor symptoms and a range of associated non-motor symptoms. Due to the heterogeneity of symptoms and variability in patient prognosis, the discovery of blood biomarkers is of utmost importance to identify the biological mechanisms underlying the different clinical manifestations of PD, monitor its progression and develop personalized treatment strategies. Whereas studies often rely on motor symptoms alone or composite scores, our study focused on finding relevant molecular markers associated with three clinical models describing either motor, cognitive or emotional symptoms. An integrative multiblock approach was performed using regularized generalized canonical correlation analysis to determine specific associations between lipidomics, transcriptomics and clinical data in 48 PD patients. We identified omics signatures confirming that clinical manifestations of PD in our cohort could be classified according to motor, cognition or emotion models. We found that immune-related genes and triglycerides were well-correlated with motor variables, while cognitive variables were linked to triglycerides as well as genes involved in neuronal growth, synaptic plasticity and mitochondrial fatty acid oxidation. Furthermore, emotion variables were associated with phosphatidylcholines, cholesteryl esters and genes related to endoplasmic reticulum stress and cell regulation.
帕金森病(PD)是临床第二常见的神经退行性疾病,以典型的运动症状和一系列相关的非运动症状为特征。由于症状的异质性和患者预后的多变性,血液生物标志物的发现对于确定PD不同临床表现的生物学机制、监测其进展和制定个性化治疗策略至关重要。虽然研究通常依赖于单独的运动症状或综合评分,但我们的研究侧重于寻找与描述运动、认知或情绪症状的三种临床模型相关的相关分子标记。采用综合多块方法,采用正则化广义典型相关分析,确定48例PD患者的脂质组学、转录组学与临床数据之间的特定关联。我们鉴定出组学特征,证实我们队列中PD的临床表现可以根据运动、认知或情绪模型进行分类。我们发现免疫相关基因和甘油三酯与运动变量密切相关,而认知变量与甘油三酯以及涉及神经元生长、突触可塑性和线粒体脂肪酸氧化的基因有关。此外,情绪变量与磷脂酰胆碱、胆固醇酯和内质网应激和细胞调节相关的基因有关。
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引用次数: 0
Serum Metabolic Profiling Identifies Key Differences between Patients with Single-Ventricle Heart Disease and Healthy Controls 血清代谢谱识别单心室心脏病患者和健康对照之间的关键差异
Pub Date : 2022-02-23 DOI: 10.3390/ijtm2010008
Julie Pires da Silva, A. Pietra, A. N. Baybayon-Grandgeorge, Anastacia M. Garcia
There are growing numbers of infants and children living with single-ventricle congenital heart disease (SV). However, cardiac dysfunction and, ultimately, heart failure (HF) are common in the SV population and the ability to predict the progression to HF in SV patients has been limited, primarily due to an incomplete understanding of the disease pathogenesis. Here, we tested the hypothesis that non-invasive circulating metabolomic profiles can serve as novel biomarkers in the SV population. We performed systematic metabolomic and pathway analyses on a subset of pediatric SV non-failing (SVNF) and failing (SVHF) serum samples, compared with samples from biventricular non-failing (BVNF) controls. We determined that serum metabolite panels were sufficient to discriminate SVHF subjects from BVNF subjects, as well as SVHF subjects from SVNF subjects. Many of the identified significantly dysregulated metabolites were amino acids, energetic intermediates and nucleotides. Specifically, we identified pyruvate, palmitoylcarnitine, 2-oxoglutarate and GTP as promising circulating biomarkers that could be used for SV risk stratification, monitoring response to therapy and even as novel targets of therapeutic intervention in a population with few other options.
有越来越多的婴儿和儿童患有单心室先天性心脏病(SV)。然而,心功能障碍和最终心力衰竭(HF)在SV人群中很常见,预测SV患者进展为HF的能力有限,主要是由于对疾病发病机制的了解不完全。在这里,我们验证了一种假设,即非侵入性循环代谢组学谱可以作为SV人群的新型生物标志物。我们对儿童SV非衰竭(SVNF)和衰竭(SVHF)血清样本进行了系统的代谢组学和途径分析,并与双心室非衰竭(BVNF)对照组的样本进行了比较。我们确定血清代谢物面板足以区分SVHF受试者和BVNF受试者,以及SVHF受试者和SVNF受试者。许多鉴定出的显著失调代谢物是氨基酸、高能中间体和核苷酸。具体来说,我们确定了丙酮酸、棕榈酰基肉碱、2-氧葡萄糖酸酯和GTP作为有希望的循环生物标志物,可用于SV风险分层、监测治疗反应,甚至在没有其他选择的人群中作为治疗干预的新靶点。
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引用次数: 2
Brixia Score in Outcomes of Alpha versus Delta Variant of Infection in Pregnant Critical COVID-19 Patients Brixia评分对妊娠COVID-19危重患者感染α变异与δ变异结局的影响
Pub Date : 2022-02-17 DOI: 10.3390/ijtm2010007
R. Covali, D. Socolov, Ioana Păvăleanu, M. Akad, L. Boiculese, R. Socolov
Background: Critical COVID-19 patients account for 1.7 to 13% of all pregnant COVID-19 patients. Methods: Patients admitted to the COVID-19 intensive care unit of Elena Doamna Obstetrics and Gynecology University Hospital in Iasi between 1 January and 1 December 2021, with critical forms of the disease, were included and retrospectively studied. The patients’ age range was 25–44 years in the Alpha group (n = 12) and 27–52 years in the Delta group (n = 9). Results: Most critically ill pregnant COVID-19 patients in the Alpha group delivered when admitted to the intensive care unit, while less than half of those in the Delta group delivered when admitted; the rest were released home and continued their pregnancy normally. There was a significant difference regarding the number of patients released to home care and the number of days after admission when delivery occurred (p = 0.02 and 0.022, respectively). Conclusions: There was no significant difference in maternal and fetal outcomes between the two groups, except for the number of patients released to home care and the number of days after admission when delivery occurred. There was no correlation between any Brixia scores (H, L, A, E) and any maternal or fetal outcomes in both groups.
背景:COVID-19危重患者占所有妊娠COVID-19患者的1.7 ~ 13%。方法:纳入2021年1月1日至12月1日在雅西Elena Doamna妇产科大学医院COVID-19重症监护室收治的危重型患者,并对其进行回顾性研究。Alpha组患者年龄为25 ~ 44岁(n = 12), Delta组患者年龄为27 ~ 52岁(n = 9)。结果:Alpha组危重妊娠COVID-19患者在入住重症监护病房时分娩的比例最高,Delta组在入住重症监护病房时分娩的比例不到一半;其余的被放回家继续正常怀孕。出院到家庭护理的患者数量和入院后分娩的天数存在显著差异(p分别= 0.02和0.022)。结论:两组之间的母婴结局无显著差异,除了出院到家庭护理的患者数量和入院后分娩的天数。在两组中,任何Brixia评分(H、L、A、E)与任何母体或胎儿结局均无相关性。
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引用次数: 2
Asymptomatic Bacteriuria or Urinary Tract Infection? New and Old Biomarkers 无症状菌尿症还是尿路感染?新旧生物标志物
Pub Date : 2022-02-01 DOI: 10.3390/ijtm2010006
F. Martino, G. Novara
Urinary tract infections (UTIs) are among the most common infective disease in the adult population. UTI diagnosis is based essentially on the presence of lower urinary tract symptoms (e.g., dysuria, urgency, and frequency) and the evidence of bacteriuria (by dipstick testing and/or urine culture). UTI diagnosis is not always easy because symptoms can be vague, or patient basal conditions can interfere negatively with the diagnostic process, whereas urine culture is still ongoing. In those cases, the differential diagnosis among UTIs and asymptomatic bacteriuria (ABU) may be challenging, while the clinician has to decide whether to start an antibiotic treatment shortly. The purpose of the present review is to analyze the biomarkers that could help in UTI diagnosis. Some biomarkers, such as procalcitonin, interleukin-6, neutrophil gelatinase-associated lipocalin, chemokines, lactoferrin, and bone morphogenetic protein-2, seem promising in UTI diagnosis, while other biomarkers failed to show any utility. Whereas a single biomarker was not enough, a combination of biomarkers could have more chances to help in the diagnosis.
尿路感染(uti)是成人最常见的感染性疾病之一。尿路感染的诊断主要基于下尿路症状(如排尿困难、尿急和尿频)和细菌尿的证据(通过试纸试验和/或尿液培养)。尿路感染的诊断并不总是容易的,因为症状可能很模糊,或者患者的基础状况可能对诊断过程产生负面影响,而尿液培养仍在进行中。在这些病例中,尿路感染和无症状细菌尿(ABU)的鉴别诊断可能具有挑战性,而临床医生必须决定是否立即开始抗生素治疗。本综述的目的是分析有助于尿路感染诊断的生物标志物。一些生物标志物,如降钙素原、白细胞介素-6、中性粒细胞明胶酶相关的脂钙蛋白、趋化因子、乳铁蛋白和骨形态发生蛋白-2,在UTI诊断中似乎很有希望,而其他生物标志物则没有显示出任何效用。然而,单一的生物标志物是不够的,生物标志物的组合可能有更多的机会帮助诊断。
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引用次数: 3
Acknowledgment to Reviewers of IJTM in 2021 感谢2021年IJTM审稿人
Pub Date : 2022-01-28 DOI: 10.3390/ijtm2010005
Rigorous peer-reviews are the basis of high-quality academic publishing [...]
严格的同行评议是高质量学术出版的基础[…]
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引用次数: 0
Artificial Intelligence and Democratization of the Use of Lung Ultrasound in COVID-19: On the Feasibility of Automatic Calculation of Lung Ultrasound Score 人工智能与新型冠状病毒肺炎肺超声使用民主化——肺超声评分自动计算的可行性探讨
Pub Date : 2022-01-13 DOI: 10.3390/ijtm2010002
Jorge Camacho, M. Muñoz, V. Genovés, J. L. Herraiz, Ignacio Ortega, Adrián Belarra, Ricardo González, David Sánchez, R.C. Giacchetta, Á. Trueba-Vicente, Y. Tung-Chen
During the COVID-19 pandemic, lung ultrasound has been revealed as a powerful technique for diagnosis and follow-up of pneumonia, the principal complication of SARS-CoV-2 infection. Nevertheless, being a relatively new and unknown technique, the lack of trained personnel has limited its application worldwide. Computer-aided diagnosis could possibly help to reduce the learning curve for less experienced physicians, and to extend such a new technique such as lung ultrasound more quickly. This work presents the preliminary results of the ULTRACOV (Ultrasound in Coronavirus disease) study, aimed to explore the feasibility of a real-time image processing algorithm for automatic calculation of the lung ultrasound score (LUS). A total of 28 patients positive on COVID-19 were recruited and scanned in 12 thorax zones following the lung score protocol, saving a 3 s video at each probe position. Those videos were evaluated by an experienced physician and by a custom developed automated detection algorithm, looking for A-Lines, B-Lines, consolidations, and pleural effusions. The agreement between the findings of the expert and the algorithm was 88.0% for B-Lines, 93.4% for consolidations and 99.7% for pleural effusion detection, and 72.8% for the individual video score. The standard deviation of the patient lung score difference between the expert and the algorithm was ±2.2 points over 36. The exam average time with the ULTRACOV prototype was 5.3 min, while with a conventional scanner was 12.6 min. Conclusion: A good agreement between the algorithm output and an experienced physician was observed, which is a first step on the feasibility of developing a real-time aided-diagnosis lung ultrasound equipment. Additionally, the examination time was reduced to less than half with regard to a conventional ultrasound exam. Acquiring a complete lung ultrasound exam within a few minutes is possible using fairly simple ultrasound machines that are enhanced with artificial intelligence, such as the one we propose. This step is critical to democratize the use of lung ultrasound in these difficult times.
在COVID-19大流行期间,肺部超声已被证明是诊断和随访肺炎(SARS-CoV-2感染的主要并发症)的有力技术。然而,作为一种相对较新的和未知的技术,缺乏训练有素的人员限制了其在世界范围内的应用。计算机辅助诊断可能有助于减少经验不足的医生的学习曲线,并更快地推广肺部超声等新技术。本文介绍了ULTRACOV(超声诊断冠状病毒病)研究的初步结果,旨在探索一种实时图像处理算法自动计算肺部超声评分(LUS)的可行性。共招募28例COVID-19阳性患者,按照肺评分方案在12个胸腔区域进行扫描,每个探针位置保存3 s视频。这些视频由经验丰富的医生和定制开发的自动检测算法进行评估,寻找a线、b线、实变和胸腔积液。专家的结果与算法之间的一致性在b线为88.0%,实变为93.4%,胸腔积液检测为99.7%,个人视频评分为72.8%。专家与算法的患者肺评分差的标准差为±2.2分/ 36。ULTRACOV原型机的平均检查时间为5.3分钟,而传统扫描仪的平均检查时间为12.6分钟。结论:算法输出与经验丰富的医生之间的一致性很好,这是开发实时辅助诊断肺部超声设备可行性的第一步。此外,检查时间减少到不到传统超声检查的一半。在几分钟内获得一个完整的肺部超声检查是可能的,使用相当简单的超声机器,通过人工智能增强,就像我们建议的那样。在这些困难时期,这一步对于普及肺部超声的使用至关重要。
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引用次数: 6
Early Neural Changes as Underlying Pathophysiological Mechanism in Diabetic Retinopathy 糖尿病视网膜病变的早期神经改变及其潜在病理生理机制
Pub Date : 2021-12-30 DOI: 10.3390/ijtm2010001
A. Cantó, Javier Martínez, Giuliana Perini-Villanueva, María Miranda, Eloy Bejarano
Diabetes mellitus is a chronic disease often accompanied by diabetic retinopathy (DR), one of the most common diabetic complications. DR is an eye condition that causes vision deficiency and often leads to blindness. DR develops when blood vessels damage the retina, the light-sensitive tissue at the back of the eye. Before changes in retinal blood vessel permeability, different molecular and anatomical modifications take place in the retina, including early neural changes. This review will summarize the current status of knowledge regarding pathophysiological mechanisms underlying DR, with a special focus on early neural modifications associated with DR. We describe hyperglycemia-associated molecular and cellular alterations linked to the initiation and progression of DR. We also discuss retinal neurodegeneration as a shared feature in different in vitro and in vivo models of DR. Given how ubiquitous diabetes is and how severe the effects of DR are, we also examine the current pharmacological and genetic approaches for combatting this disease.
糖尿病是一种慢性疾病,常伴有糖尿病视网膜病变(DR),是糖尿病最常见的并发症之一。DR是一种眼病,会导致视力不足,并经常导致失明。视网膜是眼睛后部的感光组织,当血管损伤视网膜时,DR就会出现。在视网膜血管通透性改变之前,视网膜发生了不同的分子和解剖改变,包括早期的神经变化。这篇综述将总结DR的病理生理机制的知识现状,特别关注与DR相关的早期神经改变。我们描述了与DR的开始和进展相关的高血糖相关的分子和细胞改变。我们还讨论了视网膜神经退行性变是不同DR的体外和体内模型的共同特征。我们还研究了目前对抗这种疾病的药理学和遗传学方法。
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引用次数: 1
Insights into the Function of Regulatory RNAs in Bacteria and Archaea 调控rna在细菌和古生菌中的功能研究
Pub Date : 2021-12-16 DOI: 10.3390/ijtm1030024
Elahe Soltani-Fard, Sina Taghvimi, Zahra Abedi Kichi, C. Weber, Zahra Shabaninejad, Mortaza Taheri‐Anganeh, Seyyed Hossein Khatami, P. Mousavi, A. Movahedpour, L. Natarelli
Non-coding RNAs (ncRNAs) are functional RNA molecules that comprise about 80% of both mammals and prokaryotes genomes. Recent studies have identified a large number of small regulatory RNAs in Escherichia coli and other bacteria. In prokaryotes, RNA regulators are a diverse group of molecules that modulate a wide range of physiological responses through a variety of mechanisms. Similar to eukaryotes, bacterial microRNAs are an important class of ncRNAs that play an important role in the development and secretion of proteins and in the regulation of gene expression. Similarly, riboswitches are cis-regulatory structured RNA elements capable of directly controlling the expression of downstream genes in response to small molecule ligands. As a result, riboswitches detect and respond to the availability of various metabolic changes within cells. The most extensive and most widely studied set of small RNA regulators act through base pairing with RNAs. These types of RNAs are vital for prokaryotic life, activating or suppressing important physiological processes by modifying transcription or translation. The majority of these small RNAs control responses to changes in environmental conditions. Finally, clustered regularly interspaced short palindromic repeat (CRISPR) RNAs, a newly discovered RNA regulator group, contains short regions of homology to bacteriophage and plasmid sequences that bacteria use to splice phage DNA as a defense mechanism. The detailed mechanism is still unknown but devoted to target homologous foreign DNAs. Here, we review the known mechanisms and roles of non-coding regulatory RNAs, with particular attention to riboswitches and their functions, briefly introducing translational applications of CRISPR RNAs in mammals.
非编码RNA (ncRNAs)是一种功能性RNA分子,约占哺乳动物和原核生物基因组的80%。最近的研究已经在大肠杆菌和其他细菌中发现了大量的小调控rna。在原核生物中,RNA调节因子是一组不同的分子,通过各种机制调节广泛的生理反应。与真核生物类似,细菌microrna是一类重要的ncrna,在蛋白质的发育和分泌以及基因表达的调控中起着重要作用。同样,核糖开关是一种顺式调节结构的RNA元件,能够直接控制下游基因对小分子配体的表达。因此,核糖开关检测并响应细胞内各种代谢变化的可用性。最广泛和最广泛研究的一组小RNA调节因子通过与RNA的碱基配对起作用。这些类型的rna对原核生物生命至关重要,通过修饰转录或翻译激活或抑制重要的生理过程。这些小rna中的大多数控制着对环境条件变化的反应。最后,簇状规则间隔短回文重复(CRISPR) RNA是一种新发现的RNA调节基团,含有与噬菌体和质粒序列同源的短区域,细菌利用这些同源区域拼接噬菌体DNA作为防御机制。其具体机制尚不清楚,但主要针对目标同源外源dna。在这里,我们回顾了非编码调控rna的已知机制和作用,特别关注核糖开关及其功能,简要介绍了CRISPR rna在哺乳动物中的翻译应用。
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引用次数: 5
The Action of Recombinant Human Lysosomal α-Glucosidase (rhGAA) on Human Liver Glycogen: Pathway to Complete Degradation 重组人溶酶体α-葡萄糖苷酶(rhGAA)对人肝糖原的作用:完全降解途径
Pub Date : 2021-12-14 DOI: 10.3390/ijtm1030023
A. Murray
Glycogen is present in all tissues, but it is primarily stored in the liver and in muscle. As a branched chain carbohydrate, it is broken down by phosphorylase and debrancher enzymes, which are cytoplasmic. It is also degraded by a lysosomal α-glucosidase (GAA) also known as acid α-glucosidase and lysosomal acid α-glucosidase. The deficiency of GAA in patients is known as Pompe disease, and the phenotypes as infantile, juvenile and later onset forms. Pompe disease is treated by enzyme replacement therapy (ERT) with a recombinant form of rhGAA. Following ERT in Pompe mice and human patients there is residual carbohydrate material present in the cytoplasm of cells. The goal of this work is to improve ERT and attempt to identify and treat the residual cytoplasmic carbohydrate. Initial experiments were to determine if rhGAA can completely degrade glycogen. The enzyme cannot completely degrade glycogen. There is a residual glycosylated protein as well as a soluble glycosylated protein, which is a terminal degradation product of glycogen and as such serves as a biomarker for lysosomal glycogen degradation. The glycosylated protein has a very unusual carbohydrate composition for a glycosylated protein: m-inositol, s-inositol and sorbitol as the major carbohydrates, as well as mannitol, mannose, glucose and galactose. This work describes the residual material which likely contains the same protein as the soluble glycosylated protein. The biomarker is present in serum of control and Pompe patients on ERT, but it is not present in the serum of Pompe mice not on ERT. Pompe mice not on ERT have another glycosylated protein in their serum which may be a biomarker for Pompe disease. This protein has multiple glycosylation sites, each with different carbohydrate components. These glycosylated proteins as well as the complexity of glycogen structure are discussed, as well as future directions to try to improve the outcome of ERT for Pompe patients by being able to monitor the efficacy of ERT in the short term and possibly to adjust the timing and dose of enzyme infusions.
糖原存在于所有组织中,但主要储存在肝脏和肌肉中。作为一种支链碳水化合物,它被细胞质中的磷酸化酶和脱支酶分解。它也被溶酶体α-葡萄糖苷酶(GAA)降解,也被称为酸性α-葡萄糖苷酶和溶酶体酸性α-葡萄糖苷酶。患者的GAA缺乏被称为庞贝病,其表型为婴儿期、少年期和晚发病形式。庞贝病的治疗是酶替代疗法(ERT)与重组形式的rhGAA。在Pompe小鼠和人类患者的ERT后,细胞的细胞质中存在残留的碳水化合物物质。本工作的目的是改进ERT,并尝试鉴定和处理残留的细胞质碳水化合物。最初的实验是确定rhGAA是否能完全降解糖原。这种酶不能完全降解糖原。残糖基化蛋白和可溶性糖基化蛋白是糖原的末端降解产物,因此可作为溶酶体糖原降解的生物标志物。对于糖基化蛋白来说,糖基化蛋白的碳水化合物组成非常不寻常:间肌醇、s肌醇和山梨醇是主要的碳水化合物,还有甘露醇、甘露糖、葡萄糖和半乳糖。这项工作描述了可能含有与可溶性糖基化蛋白相同的蛋白质的残留物质。该生物标志物存在于对照组和接受ERT治疗的Pompe患者的血清中,但不存在于未接受ERT治疗的Pompe小鼠的血清中。未接受ERT治疗的Pompe小鼠血清中有另一种糖基化蛋白,这可能是Pompe病的生物标志物。这种蛋白质有多个糖基化位点,每个位点都有不同的碳水化合物成分。讨论了这些糖基化蛋白以及糖原结构的复杂性,以及未来的方向,试图通过能够在短期内监测ERT的疗效,并可能调整酶输注的时间和剂量来改善Pompe患者ERT的结果。
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引用次数: 2
Hypoxia Increases Nitric Oxide-Dependent Inhibition of Angiogenic Growth 缺氧增加一氧化氮依赖性血管生成生长的抑制
Pub Date : 2021-12-08 DOI: 10.3390/ijtm1030022
Cristina Arce, Diana Vicente, F. Montó, L. González, Cristina Núñez, V. M. Víctor, F. Jiménez-Altayó, P. D’Ocon
Nitric oxide (NO) is a proangiogenic factor acting through the soluble guanylate cyclase (sGC) pathway. However, angiogenic growth increases energy demand, which may be hampered by NO inhibition of cytochrome c oxidase (CcO). Then, NO activity would be the balanced result of sGC activation (pro-angiogenic) and CcO inhibition (anti-angiogenic). NO activity in a rat and eNOS−/− mice aortic ring angiogenic model and in a tube formation assay (human aortic endothelial cells) were analyzed in parallel with mitochondrial O2 consumption. Studies were performed with NO donor (DETA-NO), sGC inhibitor (ODQ), and NOS or nNOS inhibitors (L-NAME or SMTC, respectively). Experiments were performed under different O2 concentrations (0–21%). Key findings were: (i) eNOS-derived NO inhibits angiogenic growth by a mechanism independent on sGC pathway and related to inhibition of mitochondrial O2 consumption; (ii) NO inhibition of the angiogenic growth is more evident in hypoxic vessels; (iii) in the absence of eNOS-derived NO, the modulation of angiogenic growth, related to hypoxia, disappears. Therefore, NO, but not lower O2 levels, decreases the angiogenic response in hypoxia through competitive inhibition of CcO. This anti-angiogenic activity could be a promising target to impair pathological angiogenesis in hypoxic conditions, as it occurs in tumors or ischemic diseases.
一氧化氮(NO)是一种通过可溶性鸟苷酸环化酶(sGC)途径起作用的促血管生成因子。然而,血管生成生长增加了能量需求,这可能受到NO抑制细胞色素c氧化酶(CcO)的阻碍。那么,NO活性将是sGC激活(促血管生成)和CcO抑制(抗血管生成)的平衡结果。在大鼠和eNOS - / -小鼠主动脉环血管生成模型和管形成实验(人主动脉内皮细胞)中,与线粒体O2消耗并行分析NO活性。研究分别使用NO供体(delta -NO)、sGC抑制剂(ODQ)和NOS或nNOS抑制剂(L-NAME或SMTC)进行。实验在不同O2浓度(0-21%)下进行。主要发现有:(i) enos衍生的NO通过独立于sGC途径的机制抑制血管生成生长,并与抑制线粒体O2消耗有关;(ii)一氧化氮对缺氧血管新生生长的抑制作用更为明显;(iii)在缺乏enos衍生的NO的情况下,与缺氧相关的血管生成生长调节消失。因此,一氧化氮,而不是低氧水平,通过竞争性抑制CcO来降低缺氧时的血管生成反应。这种抗血管生成活性可能是在缺氧条件下损害病理性血管生成的一个有希望的目标,因为它发生在肿瘤或缺血性疾病中。
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引用次数: 0
期刊
Journal of International Translational Medicine
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