跑台运动通过抑制小胶质细胞NAMPT表达并上调NAD+/SIRT1通路改善AD小鼠海马线粒体功能

目的:探讨12周有氧跑台运动对APP/PS1小鼠海马小胶质细胞NAMPT表达的影响及其在调节NAD^(+)/SIRT1/FOXO1/3a信号通路改善线粒体功能障碍中的作用。方法:3月龄野生型C57BL/6小鼠和APP/PS1小鼠随机分为野生型对照组(WT-sed)、野生型运动组(WT-exe)和APP/PS1对照组(AD-sed)、APP/PS1运动组(AD-exe)。运动组进行为期12周的有氧跑台运动干预。干预结束后,采用Morris水迷宫检测小鼠学习记忆能力,免疫荧光检测小鼠海马Iba-1表达水平及NAMPT与Iba-1共定位水平,透射电镜检测小鼠海马线粒体超微结构,Western blot检测海马SIRT1、Ace-FOXO1/3a、PARP1、CD38蛋白表达水平,RT-PCR检测线粒体DNA(mitochondrial DNA,mtDNA)、PARP1、CD38 mRNA表达水平,ELISA和试剂盒检测NAD^(+)、NADH、IL-1β、IL-6、TNF-α、ATP、H_(2)O_(2)的含量。结果:与WT-sed组相比,AD-sed组小鼠海马NAMPT与Iba-1共定位水平、PARP1、CD38、Ace-FOXO1/3a蛋白表达水平、IL-6、IL-1β、TNF-α、H_(2)O_(2)含量及受损线粒体数量均显著升高,NAD^(+)含量、NAD^(+)/NADH比值、SIRT1蛋白表达水平、mtDNA拷贝数、ATP含量及学习记忆能力均显著降低,而12周有氧跑台运动干预显著改善了APP/PS1小鼠海马上述异常变化。结论:12周有氧跑台运动可能通过抑制小胶质细胞NAMPT过度表达,降低神经炎症反应,减少PARP1、CD38对NAD^(+)的消耗,上调NAD^(+)/SIRT1/FOXO1/3a信号通路,改善线粒体功能障碍,最终起到缓解APP/PS1小鼠学习记忆衰退的作用。

西藏中部地区散养牦牛和绵羊细粒棘球绦虫cox1和nad1的多态性

目的分析西藏中部地区散养牦牛和绵羊细粒棘球绦虫cox1、nad1的基因多态性。方法采集西藏中部地区45份散养牦牛和绵羊细粒棘球蚴包囊,提取包囊生发层DNA,根据细粒棘球蚴线粒体cox1、nad1基因序列设计扩增的引物序列,用PCR技术扩增线粒体cox1、nad1基因片段,将扩增产物做琼脂糖凝胶电泳并测序;利用MEGA11.0软件做cox1、nad1序列特征与同源性比对,并构建系统进化树;运用DnaSP 5.0软件计算序列单倍型数量(H),分析核苷酸多样性(Pi)、单倍体型多样性(Hd)特性;利用Network软件为cox1、nad1基因的所有单倍体构建单倍体网络图,判断西藏中部地区散养牦牛和绵羊的主要单倍型。结果(1)cox1、nad1序列长度分别为925、839bp。(2)在cox1序列中,A、T、G、C碱基的平均含量分别为32.6%、33.1%、17.4%、16.9%;而nad1序列中,A、T、G、C碱基的平均含量为19.5%、47.6%、25.5%、7.4%;同源性分析结果显示,cox1序列之间的同源性为99.6%~100.0%,nad1序列之间的同源性为98.1%~100.0%;西藏中部地区散养牦牛和绵羊细粒棘球绦虫基因型为G1、G3、G6。(3)cox1、nad1单倍型个数分别为19个、7个,Hd、Pi分别为0.89600、0.56000和0.36500、0.00060。(4)单倍型网络图显示,Hc-2、Hc-12、Hn-1为西藏中部地区散养牦牛和绵羊的主要单倍型。结论西藏中部地区散养牦牛和绵羊细粒棘球绦虫基因型为G1、G3、G6,G1是主要基因型。上述结论为探明西藏中部地区细粒棘球蚴的分型和病原体遗传演化的情况提供了参考依据。

基于线粒体cox1、nad1和rrn L基因探讨马圆线科线虫间的亲缘关系

为探讨马圆线科线虫(圆线亚科和盅口亚科)间的亲缘关系,对长伞杯冠线虫(Cylicostephanus longibursatum)、冠状冠环线虫(Coronocyclus coronatus)、细口杯环线虫(Cylicocyclus leptostomus)、拉氏杯口线虫(Poteriostomum ratzii)、麦氏副杯口线虫(Parapoteriostomum mettami)和无齿圆形线虫(Strongylus edentatus)6种线虫的线粒体cox1、nad1和rrnL基因进行扩增,与同科相关线虫进行比较分析。然后以线粒体cox1、nad1和rrnL串联序列为标记基因,采用贝叶斯法(Bayesian inference,BI)构建进化树来探讨圆线科线虫间的亲缘关系。结果显示,研究中6种线虫的cox1序列长度均为1578 bp,nad1的序列长度除无齿圆形线虫为879 bp外,其余均为873 bp,rrnL序列长度均不同,大小为959~980 bp。6种线虫的cox1、nad1和rrnL的AT含量分别为67.55%~69.71%、71.36%~73.83%和80.88%~82.59%。圆线科线虫间cox1、nad1和rrnL基因的相似性分别为83.4%~97.9%、79.0%~98.4%和78.8%~98.9%。值得注意的是,圆线亚科的三齿属线虫与盅口亚科的相似性总体要高于同亚科的圆线属。进化分析显示,三齿属并没有与同亚科的圆线属形成独立分支,而是与盅口亚科线虫聚集在一起。在盅口亚科分支中,并非每一属单独形成一独立分支,冠环属和杯冠属最为明显,为复系。基于马圆线虫线粒体cox1、nad1和rrnL的序列和进化分析表明,三齿属线虫与盅口亚科的关系较圆线亚科更近,支持三齿属应隶属于盅口亚科这一假说。

黑熊源蛔虫的分子鉴定及其线粒体pcox1、pnad5基因的系统发育分析

为鉴定黑熊源蛔虫的种类及分析其系统的发育特征,本实验对长沙生态动物园黑熊肠道内分离的6株蛔虫采用PCR扩增其线粒体部分cox1基因(pcox1)和部分nad5基因(pnad5)并测序,采用DNAStar 5.0软件分析这两种基因与GenBank中不同蛔虫相应基因序列的同源性;利用Dna SP 5.0软件分析pcox1和pnad5基因的单倍型数量、核苷酸多样性以及序列之间的核苷酸差异;并采用MEGA7软件构建二者的进化树分析黑熊源蛔虫的遗传进化关系。PCR结果显示,6株黑熊源蛔虫pcox1、pnad5基因分别为408 bp和528 bp,两种基因序列之间的同源性分别为99.30%~100%和99.20~100%,与Gen Bank中转移贝蛔虫相应基因序列的同源性分别为96.80%~99.80%和95.10%~95.30%。DnaSP 5.0软件分析结果显示,黑熊源蛔虫pcox1基因共检测到5个单倍型,单倍型多样性和核苷酸多样性分别为0.933±0.015和0.00675,核苷酸差异平均值为2.733;pnad5基因共检测到6个单倍型,单倍型多样性和核苷酸多样性分别为1.000±0.00926和0.00756,平均核苷酸差异为4.000。基于pcox1和pnad5基因构建的系统进化树显示,6株黑熊源蛔虫均与转移贝蛔虫聚为同一分支;与贝氏西蛔虫聚为一大支,与其他蛔虫遗传距离较远。上述结果表明6株黑熊源蛔虫均为转移贝蛔虫,且他们的遗传变异程度均较低,pcox1基因和pnad5基因均可作为转移贝蛔虫分类鉴定的分子标记。本研究首次对黑熊源蛔虫进行分子鉴定并分析其的遗传进化关系,为转移贝蛔虫的分类鉴定以及野生黑熊蛔虫病的防治提供参考。

生物细胞内NAD水平分析技术的研究进展

烟酰胺腺嘌呤二核苷酸(NAD)是所有活细胞中普遍存在的关键辅助分子,在细胞代谢中担任着重要角色。NAD是细胞能量合成过程中的重要因子,参与DNA损伤修复,调控细胞内钙离子浓度等重要生命过程,在细胞的代谢反应中发挥着关键的作用。关于生物细胞内NAD检测的研究一直是近20年生命科学研究中的热点之一。该文从NAD结构特性、合成途径角度着手,总结了国内外关于生物细胞NAD水平检测方法的研究进展,详细介绍了各种方法的原理、优缺点及适用范围并展望了其发展趋势,以期为相关研究提供参考。

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。

奇迹女侠NAD^(+)——烟酰胺腺嘌呤二核苷酸

NAD^(+)(烟酰胺腺嘌呤二核苷酸)是一种重要的生物分子,它在细胞内起着关键的能量传递和代谢调控作用。近年来,NAD^(+)在医学和健康领域的研究备受关注,尤其是在衰老、代谢疾病和癌症治疗方面,与它相关的食物也逐渐变成了当代人们餐桌上的新宠。本文用拟人化的口吻介绍了NAD^(+)的化学结构、生物功能以及与健康相关的最新研究发展,分析了它从抗衰老领域转型临床运用的潜力。

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 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.

Association of Human Whole-blood NAD+Levels with Nabothian Cyst

Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian cysts.This study aimed to assess the association between NAD^(+)levels and nabothian cysts in healthy Chinese women.Methods Multivariate logistic regression analysis was performed to analyze the association between NAD^(+)levels and nabothian cysts.Results The mean age was 43.0±11.5 years,and the mean level of NAD^(+)was 31.3±5.3μmol/L.Nabothian cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and84(12.6%)participants,respectively.The total nabothian cyst prevalence gradually decreased from37.4%to 21.6%from Q1 to Q4 of NAD^(+)and the prevalence of single and multiple nabothian cysts also decreased across the NAD^(+)quartiles.As compared with the highest NAD^(+)quartile(≥34.4μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD^(+)Q1 was 1.89(1.14–3.14)for total nabothian cysts.The risk of total and single nabothian cysts linearly decreased with increasing NAD^(+)levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD^(+)levels of 28.0 to35.0μmol/L.Conclusion:Low NAD^(+)levels were associated with an increased risk of total and multiple nabothian cysts.

NAD+associated genes as potential biomarkers for predicting the prognosis of gastric cancer

Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly understood.We constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor prognosis.Some immune checkpoint genes were upregulated in the high-risk group.In addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk group.Notably,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk scores.Furthermore,the treatment of NMN showed increased proliferation of AGS and MKN45 cells.In addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN treatment.We conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.

Effects of different concentrations of nicotinamide on hematopoietic stem cells cultured in vitro

BACKGROUND In vitro expansion to increase numbers of hematopoietic stem cells(HSCs)in cord blood could improve clinical efficacy of this vital resource.Nicotinamide(NAM)can promote HSC expansion ex vivo,but its effect on hematopoietic stem and progenitor cells(HSPCs,CD34^(+)CD38)and functional subtypes of HSCs-shortterm repopulating HSCs(ST-HSCs,CD34^(+)CD38CD45RACD49f^(+))and long-term repopulating HSCs(LT-HSCs,CD34^(+)CD38CD45RACD49f^(+)CD90^(+))is not yet known.As a sirtuin 1(SIRT1)inhibitor,NAM participates in regulating cell adhesion,polarity,migration,proliferation,and differentiation.However,SIRT1 exhibits dual effects by promoting or inhibiting differentiation in different tissues or cells.We propose that the concentration of NAM may influence proliferation,differentiation,and SIRT1 signaling of HSCs.AIM To evaluate the effects and underlying mechanisms of action of different concentrations of NAM on HSC proliferation and differentiation.METHODS CD34^(+)cells were purified from umbilical cord blood using MacsCD34 beads,and cultured for 10-12 d in a serum-free medium supplemented with cytokines,with different concentrations of NAM added according to experimental requirements.Flow cytometry was used to detect phenotype,cell cycle distribution,and apoptosis of the cultured cells.Real-time polymerase chain reaction was used to detect the transcription levels of target genes encoding stemness-related factors,che mokines,components of hypoxia pathways,and antioxidant enzymes.Dichloro-dihydro-fluorescein diacetate probes were used to evaluate intracellular production of reactive oxygen species(ROS).Determination of the effect of different culture conditions on the balance of cytokine by cytometric bead array.RESULTS Compared with the control group,the proportion and expansion folds of HSPCs(CD34^(+)CD38)incubated with 5 mmol/L or 10 mmol/L NAM were significantly increased(all P<0.05).The ST-HSCs ratio and fold expansion of the 5 mmol/L NAM group were significantly higher than those of the control and 10 mmol/L NAM groups(all P<0.001),whereas the LT-HSCs ratio and fold expansion of the 10 mmol/L NAM group were significantly higher than those of the other two groups(all P<0.05).When the NAM concentration was>10 mmol/L,cell viability significantly decreased.In addition,compared with the 5 mmol/L NAM group,the proportion of apoptotic cells in the 10 mmol/L NAM group increased and the proportion of cells in S and G2 phase decreased.Compared with the 5 mmol/L NAM group,the HSCs incubated with 10 mmol/L NAM exhibited significantly inhibited SIRT1 expression,increased intracellular ROS content,and downregulated expression of genes encoding antioxidant enzymes(superoxide dismutase 1,peroxiredoxin 1).CONCLUSION Low concentrations(5 mmol/L)of NAM can better regulate the balance between proliferation and differentiation,thereby promoting expansion of HSCs.These findings allow adjustment of NAM concentrations according to expansion needs.

年龄对眼周NAD(P)H水平影响及一款眼霜抗皱功效评价

通过招募一批不同年龄段受试者,使用皮肤无创仪器检测方法分析眼周NAD(P)H水平与年龄、肤色和弹性参数R2之间的相关性。另招募一批受试者,使用一款眼霜评估眼部抗皱效果。研究结果表明:随着年龄增长,眼周颗粒层细胞NAD(P)H水平降低、鱼尾纹等级增大,皮肤弹性R2值减小,肤色加深,皮肤ITA°值减小。年龄、肤色、弹性与NAD(P)H水平之间存在相关性。15名受试者使用眼霜28天后,与使用前相比眼周NAD(P)H水平增加,皮肤弹性R2值增加,鱼尾纹评级下降,胶原纤维谐波强度增加。该产品具有一定的抗皱效果。

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.

利用不同方法将小分子NADPH转染进入细胞的比较

目的利用非代谢途径直接将外源小分子烟酰胺腺嘌呤二核苷酸磷酸(NADPH)转染进入细胞内的方法。方法对比3种不同转染试剂(X-tremeGENE TM HP DNA、Lipofectamine TM RNAiMAX和Lipofectamine TM 2000)将NADPH转染到人骨肉瘤细胞系U2OS和小鼠胚胎成纤维细胞系3T3L1中的效果,并通过油红O染色比较它们对脂肪细胞分化的影响。结果用X-tremeGENE HP DNA转染试剂转染NADPH可以有效提高细胞内NADPH水平(P<0.001)。随着NADPH转染浓度(10μmol/L NADPH与10μL转染试剂)的增加,细胞中的NADPH水平呈剂量依赖性增加。此外使用3种转染试剂在3T3L1前脂肪细胞中转染NADPH,只有使用X-tremeGENE HP DNA转染试剂转染NADPH的脂肪细胞分化更明显(P<0.001)。结论X-tremeGENE HP DNA转染试剂能够成功地将外源NADPH转染进入细胞内,并促进3T3L1脂肪细胞的分化和脂质积累。

Dynamic Non-Invasive Detection of NADH Based on Blood Flow-Mediated Skin Fluorescence (FMSF) Method

Nicotinamide adenine dinucleotide (NADH/NAD+) is involved in important biochemical reactions in human metabolism, including participation in energy production by mitochondria. The changes in fluorescence intensity as a function of time in response to blocking and releasing of blood flow in a forearm are used as a measure of oxygen transport with blood to the tissue, which directly correlates with the skin microcirculation status. In this paper, a non-invasive dynamic monitoring system based on blood flow-mediated skin fluorescence (FMSF) technology is developed to monitor the NADH fluorescence intensity of skin tissue during the process of blocking reactive hyperemia. Simultaneously, laser speckle contrast imaging (LSCI) and laser Doppler flowmetry (LDF) were used to observe blood flow, blood oxygen saturation (SOt2) and relative amount of hemoglobin (rHb) during the measurement process, which helped to explore NADH dynamics relevant physiological changes. A variety of parameters have been derived to describe NADH fluorescence curve based on the FMSF device. The experimental results are conducive to understanding the NADH measurement and the physiological processes related to it, which help FMSF to be a great avenue for in vivo physiological, clinical and pharmacological research on mitochondrial metabolism.

NADPH氧化酶导致糖尿病肾病病理改变机制的研究进展

烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶是引发糖尿病肾病病理改变的重要因素,通过氧化应激反应作用于肾脏。对NADPH氧化酶的研究成为近年热点。本文对NADPH氧化酶导致糖尿病肾病病理改变机制进行综述。

超声弹性成像联合血清Mac-2结合蛋白糖基化异构体、NADPH氧化酶2对慢性乙型肝炎患者肝纤维化的诊断价值

目的探讨超声弹性成像联合血清Mac-2结合蛋白糖基化异构体(Mac-2 binds protein glycosylated isomers,M2BPGi)、还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(NADPH oxidase 2,NOX2)对慢性乙型肝炎(chronic hepatitis B,CHB)患者肝纤维化的诊断价值。为肝纤维化的诊断提供参考依据。方法选取宜昌市第三人民医院于2021年1月—2023年3月期间收治的175例CHB患者为研究对象,并根据肝纤维化程度分为非显著性肝纤维化组(n=67)和显著性肝纤维化组(n=108)。多因素Logistic回归分析法分析发生显著性肝纤维化的影响因素;超声弹性成像联合血清M2BPGi、NOX2水平对显著性肝纤维化的诊断价值采用受试者工作特征(receiver operating characteristic,ROC)曲线分析。结果非显著性肝纤维化组和显著性肝纤维化组丙氨酸氨基转移酶(alanine transaminase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、白蛋白(albumin,ALB)和血小板计数(platelet count,PLT)比较差异均具有统计学意义(P均<0.05);与非显著性肝纤维化组比较,显著性肝纤维化组患者应变均值(mean strain value,MEAN)和峰度明显较低(P<0.05),偏度、复杂度(complexity,COMP)、对比度、标准差、蓝色区域面积比(ratio of blue area,AREA)和血清M2BPGi和NOX2水平均明显较高(P<0.05)。血清M2BPGi、NOX2、ALT、COMP、AREA是影响CHB患者发生显著性肝纤维化的独立危险因素,而PLT和MEAN是其保护因素(P<0.05)。ROC分析结果显示,M2BPGi、NOX2、MEAN、COMP和AREA联合诊断显著性肝纤维化的AUC为0.933,显著大于各指标单独诊断的AUC(P<0.05)。结论M2BPGi和NOX2在发生显著性肝纤维化的CHB患者血清中的水平较高,2者联合超声弹性成像对显著性肝纤维化具有较高的诊断价值。

NAD^(+)代谢机制及其对衰老相关疾病影响研究进展

综述NAD^(+)代谢机制及其对衰老相关疾病的影响研究进展。重点从NAD^(+)的生物合成途径、消耗途径及其调控机制等方面阐述NAD^(+)参与的信号通路和细胞过程,以及它在健康与疾病中的作用,并且以NAD^(+)代谢网络中前体物质和关键酶的作用机理为依据,探讨NAD^(+)代谢调控在衰老相关疾病中的潜在治疗方法,为理解NAD^(+)水平下降和衰老相关疾病之间复杂的因果关系提供新的视角;同时从NAD^(+)及其前体的分布和运输、有毒代谢物的产生和修复、NAD^(+)代谢动态的监测和测量等方面阐述NAD^(+)研究发展过程中存在的瓶颈。最后展望以NAD^(+)为靶点进行疾病治疗和药物开发的广阔前景。

NAD依赖型去乙酰化酶SRT在植物表观遗传调控中的作用

SRT(sirtuin)是一类与酵母沉默信息调节蛋白2(yeast silent information regulator 2, Sir2)高度同源的烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide, NAD)依赖型蛋白质去乙酰化酶。真核生物中,SRT通过催化特异组蛋白或非组蛋白赖氨酸(Lys)残基的去乙酰化反应,调控染色体稳定、基因转录及相关蛋白的活性状态。研究表明,SRT介导的去乙酰化在植物代谢、生长发育和逆境胁迫响应等过程中起重要作用。本文对植物SRT的鉴定、结构与分类、生物进化、表观遗传调控机制和生物学过程调控方面的研究加以综述,并对该蛋白未来研究方向进行展望,以期为今后SRT介导的表观遗传学生物过程的研究提供基础。