Nicotinamide adenine dinucleotide treatment confers resistance to neonatal ischemia and hypoxia:effects on neurobehavioral phenotypes

Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

Nicotinamide adenine dinucleotide phosphate oxidase in pancreatic diseases:Mechanisms and future perspectives

Pancreatitis and pancreatic cancer(PC)stand as the most worrisome ailments affecting the pancreas.Researchers have dedicated efforts to unraveling the mechanisms underlying these diseases,yet their true nature continues to elude their grasp.Within this realm,oxidative stress is often believed to play a causal and contributory role in the development of pancreatitis and PC.Excessive accumulation of reactive oxygen species(ROS)can cause oxidative stress,and the key enzyme responsible for inducing ROS production in cells is nicotinamide adenine dinucleotide phosphate hydrogen oxides(NOX).NOX contribute to pancreatic fibrosis and inflammation by generating ROS that injure acinar cells,activate pancreatic stellate cells,and mediate macrophage polarization.Excessive ROS production occurs during malignant transformation and pancreatic carcinogenesis,creating an oxidative microenvironment that can cause abnormal apoptosis,epithelial to mesenchymal transition and genomic instability.Therefore,understanding the role of NOX in pancreatic diseases contributes to a more in-depth exploration of the exact pathogenesis of these diseases.In this review,we aim to summarize the potential roles of NOX and its mechanism in pancreatic disorders,aiming to provide novel insights into understanding the mechanisms underlying these diseases.

Oral Administration of Nicotinamide Mononucleotide with Bioenhancer BioPerine® Increases the Serum Concentration of Nicotinamide Adenine Dinucleotide in Healthy Human Volunteers: A Pilot, Open-Label, Cross-Over Study

Background: Bioenhancers augment the bioavailability of co-administered molecules without showing any significant effect on their own. Piperine, an alkaloid from Piper nigrum, is an established natural bioenhancer. Nicotinamide mononucleotide (NMN), an antiaging supplement, is the precursor of coenzyme nicotinamide adenine dinucleotide (NAD) that plays an important role in intracellular redox reactions. Objective: The study compared the serum concentrations of NAD in normal healthy participants, supplemented with NMN 500 mg and NMN 500 mg + 5 mg BioPerine® (95% piperine). Methods: In a randomized, open-label, crossover study, NMN (500 mg) was compared to NMN + BioPerine® (500 mg + 5 mg) in 6 healthy adults, aged 18 - 45 years. The participants received a single oral dose of NMN or NMN + BioPerine® capsules with 240 mL water, and blood samples were collected over 8hr. After a 4-day washout period, the same procedures were repeated as per the crossover design. Total NAD (NADtotal), including oxidized NAD (the oxidized) and its reduced form NADH, was measured in human serum samples. Results: The maximum concentration (Cmax) of NAD in serum was higher with NMN + BioPerine® (282 pmol/mL) compared to NMN (246 pmol/mL) alone. In the presence of BioPerine®, the NAD concentrations reached 257 pmol/mL during the first 2 hr, whereas a comparable serum concentration (246 pmol/mL) was attained only after 6 hr in NMN alone. The AUC0-8hr was 1738 pmol/mL/hr in NMN compared to 2004 pmol/mL/hr in NMN+ BioPerine®. The time to reach peak concentration (t1/2) was similar (6hr) in both groups. No clinically relevant adverse events (AE) were observed, and safety parameters remained within normal ranges in all the participants with both formulations. Conclusion: These results reveal that BioPerine® can effectively increase the NAD concentrations in the serum following NMN supplementation in healthy volunteers. The present study was registered prospectively with the Clinical Trials Registry-India (CTRI/2023/11/059982).

Nicotinamide adenine dinucleotide phosphate oxidase activation and neuronal death after ischemic stroke

Nicotinamide adenine dinucleotide phosphate oxidase(NOX) is a multisubunit enzyme complex that utilizes nicotinamide adenine dinucleotide phosphate to produce superoxide anions and other reactive oxygen species. Under normal circumstances, reactive oxygen species mediate a number of important cellular functions, including the facilitation of adaptive immunity. In pathogenic circumstances, however,excess reactive oxygen species generated by NOX promotes apoptotic cell death. In ischemic stroke, in particular, it has been shown that both NOX activation and derangements in glucose metabolism result in increased apoptosis. Moreover, recent studies have established that glucose, as a NOX substrate, plays a vital role in the pathogenesis of reperfusion injury. Thus, NOX inhibition has the potential to mitigate the deleterious impact of hyperglycemia on stroke. In this paper, we provide an overview of this research,coupled with a discussion of its implications for the development of NOX inhibition as a strategy for the treatment of ischemic stroke. Both inhibition using apocynin, as well as the prospect of developing more specific inhibitors based on what is now understood of the biology of NOX assembly and activation, will be highlighted in the course of our discussion.

OTOTOXIC MODEL OF OXALIPLATIN AND PROTECTION FROM NICOTINAMIDE ADENINE DINUCLEOTIDE

Oxaliplatin, an anticancer drug commonly used to treat colorectal cancer and other tumors, has a number of serious side effects, most notably neuropathy and ototoxicity. To gain insights into its ototoxic profile, oxaliplatin was applied to rat cochlear organ cultures. Consistent with it neurotoxic propensity, oxaliplatin selectively damaged nerve fibers at a very low dose 1 μM. In contrast, the dose required to damage hair cells and spiral ganglion neurons was 50 fold higher (50 μM). Oxailiplatin-induced cochlear lesions initial-ly increased with dose, but unexpectedly decreased at very high doses. This non-linear dose response could be related to depressed oxaliplatin uptake via active transport mechanisms. Previous studies have demon-strated that axonal degeneration involves biologically active processes which can be greatly attenuated by nicotinamide adenine dinucleotide (NAD+). To determine if NAD+would protect spiral ganglion axons and the hair cells from oxaliplatin damage, cochlear cultures were treated with oxaliplatin alone at doses of 10 μM or 50 μM respectively as controls or combined with 20 mM NAD+. Treatment with 10 μM oxaliplatin for 48 hours resulted in minor damage to auditory nerve fibers, but spared cochlear hair cells. However, when cochlear cultures were treated with 10 μM oxaliplatin plus 20 mM NAD+, most auditory nerve fibers were intact. 50 μM oxaliplatin destroyed most of spiral ganglion neurons and cochlear hair cells with apop-totic characteristics of cell fragmentations. However, 50 μM oxaliplatin plus 20 mM NAD+treatment great-ly reduced neuronal degenerations and hair cell missing. The results suggested that NAD+provides signifi-cant protection against oxaliplatin-induced neurotoxicity and ototoxicity, which may be due to its actions of antioxidant, antiapoptosis, and energy supply.

Studies on Synthesis of Stationary Phase Containing Nicotinamide Adenine Dinucleotide(NAD) Bonded to Phospholipid-Coated Aminated Silica for HPLC

Recently biospecific affinity chromatography has been widely used for the separation and purification of various enzymes and nucleic acids. In this paper, a series of synthetic reactions of solid-liquid phase were carried out on silica surface, using a macroporous(30 mu m), microspherical silica (8 mu m) as the matrix and gamma-aminopropyltriethoxysilane as the activating agent, the nicotinamide adenine dinucleotide(NAD) was bonded through its amino groups to the carboxylic groups of linked phospholipid which was bonded covalently on aminated support. The bonded stationary phase has high thermal stability, and could be used to separate of nucleotides with good resolution.

Nicotinamide Adenine Dinucleotide and Adenosine Triphosphate Oscillations Caused by Gradual Entry of Substrates within Mitochondria

Nicotinamide adenine dinucleotide (NAD) oscillation was observed when the isolated mitochondria were immersed in a pyruvate solution. In addition, when an adenosine diphosphate (ADP) was added to the mitochondrial suspension containing pyruvate, adenosine triphosphate (ATP) oscillation was observed as well as NADH oscillation. At this time, the pH within mitochondria also oscillated. It was found that the oscillatory reaction of NADH caused by the membrane permeation of pyruvate continues, causing the oscillation of NADH and H+ in the subsequent reactions. The pH oscillation led to the ATP oscillation. It is considered that the oscillatory reaction caused by the gradual entry of pyruvate into mitochondria was thought to be carried over to both the citric acid cycle and the respiratory chain, ultimately leading to the ATP oscillation in oxidative phosphorylation. Similarly, it was found that membrane permeation of malate causes the gradual occurrence of NADH, at which point NADH oscillates, followed by an oscillatory reaction of the respiratory chain, and finally ATP oscillation. It was found that the oscillations of NADH and ATP occur without going through the citric acid cycle. Oscillations of NADH and other intermediates in both the citric acid cycle and respiratory chain were also confirmed by experiments using semipermeable membranes. These results support our hypothesis that the gradual entry of the substrate by membrane permeation triggers an oscillatory reaction of the enzyme, which is also carried over to subsequent reactions.

Nicotinamide adenine dinucleotide(NAD^(+))reduction enabled by an atomically precise Au-Ag alloy nanocluster

The redox property of the ultrasmall coinage nanoclusters(with several to tens of Au/Ag atoms)has elucidated the electrontransfer capacity of nanoclusters,has been successfully utilized in a variety of redox conversions(such as from CO_(2)to CO).Nevertheless,their biological applications are mainly restricted by the scarcity of atomically precise,water-soluble metal nanoclusters,the limited application(mainly on the decomposition of H_(2)O_(2)in these days).Herein,mercaptosuccinic acid(MSA)protected ultrasmall alloy AuAg nanoclusters were prepared,the main product was determined[Au_(3)Ag_(5)(MSA)_(3)]−by electrospray ionization mass spectrometry(ESI-MS).The clusters can not only mediate the decomposition of H_(2)O_(2)to generate hydroxyl radicals,but is also able to mediate the reduction of nicotinamide adenine dinucleotide(NAD)to its reduced form of NADH.This is the first time that the atomically precise metal nanoclusters were used to mediate the coenzyme reduction.The preliminary mechanistic insights imply the reaction to be driven by the hydrogen bonding between the carboxylic groups(on the surface of MSA)and the amino N–H bonds(on NAD).In this context,the presence of the carboxylic groups,the sub-nanometer size regime(~1 nm),the synergistic effect of the Au-Ag clusters are pre-requisite to the NAD reduction.

Panax Notoginseng Saponins Inhibits Atherosclerotic Plaque Angiogenesis by Down-Regulating Vascular Endothelial Growth Factor and Nicotinamide Adenine Dinucleotide Phosphate Oxidase Subunit 4 Expression

Objective： To investigate the mechanism of Panax notoginseng saponins （PNS）, an effective component extracted from Panax notoginseng, on atherosclerotic plaque angiogenesis in atherosclerosis-prone apolipoprotein E-knockout （ApoE-KO） mice fed with high-fat, high-cholesterol diet. Methods： Twenty ApoE-KO mice were divided into two groups, the model group and the PNS group. Ten normal C57BL/6J mice were used as a control group. PNS （60 mg/kg） was orally administered daily for 12 weeks in the PNS group, The ratio of plaque area to vessel area was examined by histological staining. The tissue sample of aortic root was used to detect the CD34 and vascular endothelial growth factor （VEGF） expression areas by immunohistochemistry. The expression of VEGF and nicotinamide adenine dinucleotide phosphate oxidase subunit 4 （NOX4） were measured by reverse transcription polymerase chain reaction and Westem blotting respectively. Results： After treatment with PNS, the plaque areas were decreased （P〈0.05）. CD34 expressing areas and VEGF expression areas in plaques were significantly decreased （P〈0.05）. Meanwhile, VEGF and NOX4 mRNA expression were decreased after treatment with PNS, VEGF and NOX4 protein expression were also decreased by about 72% and 63%, respectively （P〈0.01）. Conclusion： PNS, which decreases VEGF and NOX4 expression, could alleviate plaque angiogenesis and attenuate atherosclerosis.

Relationship between reduced nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox gene polymorphism and obstructive sleep apnea-hypopnea syndrome in the Chinese Han population

Background Increased production of reactive oxygen species （ROS） is thought to play a major role in the pathogenesis of obstructive sleep apnea-hypopnea syndrome （OSAHS）. The reduced nicotinamide adenine dinucleotide phosphate （NADPH） oxidase complex is an important source of ROS. The p22phox subunit is polymorphic with a C242T variant that changes histidine-72 for a tyrosine in the potential heme binding site. This study aimed to investigate the relationship between NADPH oxidase subunit p22phox gene polymorphism and OSAHS. Methods The genotypes of p22phox polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphisms （PCR-RFLP） assay in 176 unrelated subjects of the Han population in southern region of China （including 107 OSAHS subjects and 69 non-OSAHS subjects）, while the plasma concentration of superoxide dismutase （SOD） was detected in the two groups, and p22phox mRNA expression in peripheral blood mononuclear cell （PBMC） was determined with reverse transcription polymerase chain reaction （RT-PCR）. Results The phagocyte NADPH oxidase subunit p22phox mRNA expression was significantly increased in the OSAHS group than that in the non-OSAHS group （P 〈0.01）. Compared with the non-OSAHS control group （（85.31±9.23） U/ml）, the levels of SOD were lower in patients with OSAHS （（59.65±11.61） U/ml （P 〈0.01）. There were significant differences in genotypes distribution in p22phox polymorphism between the two groups （P=0.02）. Compared with the non-OSAHS control group, the OSAHS group had a significantly higher T allele frequency in p22phox polymorphism （P=0.03）. There were independent effects of p22phox polymorphism on body mass index （BMI）, neck circumference （NC）, waist-to-hip ratio （WHR） in the OSAHS group, and the carriers of the T allele of p22phox polymorphism had greater NC, WHR, systolic blood pressure （SBP）, diastolic blood pressure （DBP） and apnea-hypopnea index （AHI） （P 〈0.05）, but the carriers of the T allele had lower SOD （P 〈0.01） and lowest SaO2 （P=0.04）. There was no significant difference in p22phox mRNA expression between the OSAHS groups with or without T allele （P=0.45）. Conclusions The NADPH oxidase subunit p22phox gene polymorphism may be associated with susceptibility to OSAHS, and it may be an important candidate gene for OSAHS.

Drought-Stimulated Activity of Plasma Membrane Nicotinamide Adenine Dinucleotide Phosphate Oxidase and Its Catalytic Properties in Rice

The activity of plasma membrane （PM） nicotinamide adenine dinucleotide phosphate （NADPH） oxidase and its catalytic properties in rice was investigated under drought stress conditions. Drought stress led to decreased leaf relative water content （RWC） and, as a result of drought-induced oxidative stress, the activities of antioxidant enzymes increased significantly. More interestingly, the intensity of applied water stress was correlated with increased production of H2O2 and O2^- and elevated activity of PM NADPH oxidase, a key enzyme of reactive oxygen species generation in plants. Histochemical analyses also revealed increased H2O2 and O2^- production in drought-stressed leaves. Application of diphenylene iodonium （DPI）, an inhibitor of PM NADPH oxidase, did not alleviate drought-induced production of H2O2 and O2^-. Catalysis experiments indicated that the rice PM NADPH oxidase was partially fiavin-dependent. The pH and temperature optima for this enzyme were 9.8 and 40 ℃, respectively. In addition, drought stress enhanced the activity under alkaline pH and high temperature conditions. These results suggest that a complex regulatory mechanism, associated with the NADPH oxidase-H2O2 system, is involved in the response of rice to drought stress.

Excessive Copper Induces the Production of Reactive Oxygen Species,which is Mediated by Phospholipase D, Nicotinamide Adenine Dinucleotide Phosphate Oxidase and Antioxidant Systems

Tobacco BY-2 suspension cells were used to study the chemical damage and its associated mechanisms caused by Cu^2＋. Treatment with 100 μmol/L Cu^2＋ generated a large amount of HzOz and thiobarbituric acid-reactive substances （TBARS） in cells. Using phospholipase D （PLD） specific inhibitor （1-butanol） or phosphatidic acid （PA）, we demonstrated that PLD plays an important role in the generation of H2O2 and TBARS. Semi-quantitative reverse-transcriptase polymerase chain reaction and enzyme activity assays with wild type and nicotinamide adenine dinucleotide phosphate （NADPH） oxidaseoverexpressing BY-2 cells revealed that PLD and PA are the key factors leading to NADPH oxidase activation, which is responsible for H2O2 and TBARS production induced by Cu^2＋. Moreover, the content of ascorbic acid （AsA）, an effective antioxidant, was sharply reduced in BY-2 cells exposed to excessive Cu^2＋. Furthermore, a significant downregulation of the enzymes of AsA biosynthesis and the antioxidant system was found. This evidence suggests that excessive Cu^2＋-elevated reactive oxygen species （ROS） production is caused by upregulated PLD that elevates the activity of NADPH oxidase and its collapsed antioxidant systems that scavenges ROS.

The effects of nicotinamide adenine dinucleotide in cardiovascular diseases: Molecular mechanisms, roles and therapeutic potential

Recently, cardiovascular diseases (CVDs) were identified as the leading cause of mortality, imposing a heavy burden on health care systems and the social economy. Nicotinamide adenine dinucleotide (NAD+), as a pivotal co-substrate for a range of different enzymes, is involved in many signal transduction pathways activated in CVDs. Emerging evidence has shown that NAD+ can exert remediating effects on CVDs by regulating metabolism, maintaining redox homeostasis and modulating the immune response. In fact, NAD+ might delay ageing through sirtuin and non-sirtuin pathways and thus contribute to interventions for age-related diseases such as CVDs. Considering that robust clinical studies of NAD+ are ongoing, we discuss current challenges and the future translational potential of NAD+ based on existing studies and our understanding. Despite some remaining gaps in its clinical application, NAD+ has been shown to have broad prospects and pan-effects, making it a suitable prophylactic drug for CVDs.

Association of nicotinamide adenine dinucleotide phosphate oxidase p22phox gene 549C〉T polymorphism with coronary artery disease

Background The p22phox is a critical component of the superoxide-generating vascular nicotinamide adenine dinucleotide phosphate （NADPH） oxidase. Several polymorphisms in p22phox gene are studied for their association with cardiovascular diseases. However, no publication is available to assess the relation of 549C〉T polymorphism in p22pho~ gene to coronary artery disease （CAD） risk. This study was to investigate the effect of the p22phox gene 549C〉T polymorphism on CAD risk. Methods Hospital-based case-control study was conducted with 297 CAD patients and 343 healthy persons as the control group. Polymerase chain reaction and pyrosequencing using PSQ 96 MA Pyrosequencer （Biotage AB） were used to detect the polymorphisms. Multiple Logistic regression model was used to adjust the potential confounders and to estimate odds ratio （OR） with 95% confidence intervals （CIs）. Results The observed genotype frequencies of this polymorphism obeyed the Hardy-Weinberg equilibrium in both cases （P=0.439） and controls （P=-0.668）. The frequency of mutant genotypes （＇I-I-＋CT） in cases （41.08%） was higher than that in controls （36.73%） with an OR=1.20 （95% C1=0.87-1.65）. After the adjustment of the potential confounders, there was a significant association of the mutant genotypes with increased risk of CAD （OR=1.57, 95% C1=1.01-2.46, P=0.047）. Conclusions The mutant genotypes of the p22phox gene 549C〉T polymorphism had a significant effect on the increased risk of CAD in this studied population.

Pioglitazone inhibits the expression of nicotinamide adenine dinucleotide phosphate oxidase and p38 mitogen-activated protein kinase in rat mesangial cells

Background Oxidative Stress and p38 mitogen-activated protein kinase （p38MAPK） play a vital role in renal fibrosis. Pioglitazone can protect kidney but the underlying mechanisms are less clear. The purpose of this study was to investigate the effect of pioglitazone on oxidative stress and whether the severity of oxidative stress was associated with the phosphorylation level of p38MAPK.

NAD^(+)代谢途径在炎症性肠病治疗中的研究进展

炎症性肠病(IBD)包括溃疡性结肠炎(UC)和克罗恩病(CD),是一种全身性炎症性疾病。烟酰胺腺嘌呤二核苷酸(NAD^(+))被广泛用作生化反应的辅助因子或底物,与身体健康密切相关。IBD与NAD^(+)之间的密切关系已得到广泛的认识,肠道稳态依赖于NAD^(+)合成与分解的平衡,针对NAD^(+)通路的治疗方法有望用于IBD的治疗。本文就NAD^(+)代谢途径在IBD治疗中的研究进展作一综述,从而为NAD^(+)相关疗法在IBD治疗中的应用提供方向。

NDUFS6蛋白生物信息学分析及过表达质粒的构建与鉴定

目的 应用生物信息学方法分析线粒体呼吸链复合体Ⅰ结构亚基烟酰胺腺嘌呤二核苷酸脱氢酶(泛素)铁硫蛋白6(NDUFS6)的理化性质,构建pCV702-NDUFS6过表达质粒并进行鉴定,为进一步研究NDUFS6蛋白功能奠定基础。方法 利用Expasy、UniProtKB、NCBI、SOPMA等生物信息学工具分析NDUFS6蛋白的理化性质、二级结构等;根据NDUFS6 cDNA序列构建携带NDUFS6基因的过表达质粒pCV702-NDUFS6,转染大鼠心肌细胞H9C2,并设置阴性对照(NC)组和相应空载体CON520作为阳性对照(PC)组,经嘌呤霉素筛选后,采用RT-qPCR和Western blot检测NDUFS6 mRNA和蛋白表达水平。结果 NDUFS6蛋白由116个氨基酸组成,理论等电点pI为9.37。蛋白二级结构以无规则卷曲(占50%)为主。酶切鉴定和基因测序结果显示,pCV702-NDUFS6表达质粒构建成功。RT-qPCR和Western blot结果显示,相较于NC组和PC组,过表达组NDUFS6表达水平均上调(P均<0.05)。结论 成功构建了能在心肌细胞H9C2中有效过表达NDUFS6基因的过表达质粒。

血清Nox2、ATG7水平对新生儿窒息心肌损伤的评估价值

目的探讨自噬相关基因-7(ATG7)、烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(Nox2)在新生儿窒息病儿血清中的表达及早期诊断价值。方法选取2019年1月至2021年12月在郑州大学第三附属医院产科分娩的75例新生儿窒息病儿为研究组,根据是否合并心肌损伤将病儿分为窒息心肌损伤组31例,窒息非心肌损伤组44例。同期选择50例健康足月新生儿为对照组。收集一般资料,采用酶联免疫吸附测定(ELISA)测量血清ATG7水平,采用蛋白质印迹法检测Nox2水平,以Nox2/β肌动蛋白的灰度比值为Nox2表达量;采用Pearson法分析ATG7、Nox2表达的相关性及与各指标的相关性;利用受试者操作特征曲线(ROC曲线)评价Nox2、ATG7水平对新生儿窒息心肌损伤的诊断价值。结果与对照组[0.26±0.06、(4.83±0.61)ng/L]比较,新生儿窒息病儿血清Nox2(0.65±0.09)、ATG7[(21.04±3.66)ng/L]表达水平升高,且窒息心肌损伤组[0.85±0.11、(24.23±3.98)ng/L]病儿血清中Nox2、ATG7水平高于窒息非心肌损伤组[0.51±0.08、(18.80±3.43)ng/L](P<0.05);窒息心肌损伤病儿血清中Nox2、ATG7表达呈显著正相关(r=0.57,P<0.05);病儿血清中Nox2和ATG7表达与肌酸激酶同工酶(CK-MB)、缺血修饰白蛋白(IMA)、超敏C-反应蛋白(hs-CRP)、氨基末端脑钠肽前体(NT-ProBNP)、肌钙蛋白I(cTnI)、肌红蛋白表达均呈正相关(P<0.05);ROC曲线结果显示,血清Nox2、ATG7水平预测新生儿窒息合并心肌损伤的曲线下面积(AUC)及其95%CI分别为0.91(0.82,0.96)、0.89(0.80,0.95),对应的灵敏度分别为83.87%、87.10%,特异度分别为84.09%、75.00%,二者联合预测的AUC及其95%CI为0.92(0.84,0.97),灵敏度为90.32%,特异度为81.82%。结论窒息心肌损伤病儿血清中Nox2、ATG7表达均上调,二者联合检测对窒息心肌损伤有一定的诊断价值。

NADPH氧化酶4在心血管损伤中的作用机制

心血管结构和功能损伤是许多心血管疾病的重要病理基础,许多研究表明氧化应激在缺血性心脏病、动脉粥样硬化、高血压等诸多病理性心血管损伤中发挥重要作用。NADPH氧化酶(Nox)是调控氧化还原信号的关键酶,而血管内的活性氧主要来源于Nox4。随着研究的不断深入,发现Nox4在不同阶段或不同刺激下会发挥不同甚至截然相反的作用,如双向调节动脉粥样硬化的进展、双向作用影响血压等。现总结Nox4在不同心血管损伤中的不同影响及作用机制,为后续的研究提供一定的理论基础。

NAD^+对受照射L02肝细胞株bcl-2、bax、p53蛋白表达的影响

目的:探讨氧化型烟酰胺腺嘌呤二核苷酸对体外培养的人正常肝细胞株L02辐射损伤保护作用及可能的机制。方法:实验分3组,照射+NAD组、照射组和假照射组。采用MTT法检测NAD+对受照射L02细胞生长活性的影响;应用流式细胞仪检测各组细胞凋亡率以及凋亡相关蛋白bax、bcl-2、p53阳性表达率。结果:细胞受照射后加入NAD+能够对抗X射线照射对L02细胞的生长抑制作用,细胞生长活性较单照射组细胞活性显著提高、减少细胞凋亡(P<0.05);照射后加NAD+组与照射组相比较,细胞p53、bax表达下调(P<0.05)、bcl-2的表达上调(P<0.05)。结论:NAD+可以对抗L02细胞的X线辐射损伤,其作用机制很可能与P53信号传递途径有关。