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Nampt与消化系统肿瘤关系的研究进展

广东医学 2016年第3期37卷 451-454页

作者：雷焦姚克诚章园三峡大学人民医院、湖北省宜昌市第一人民医院普通外科 443000 三峡大学人民医院、湖北省宜昌市第一人民医院综合内科 443000

尼克酰胺磷酸核糖转移酶（nicotinamide phosphoribosyltransferase,Nampt）最初称为前B细胞克隆增强因子（preB-cell colony-enhancing factor,PBEF）,是从激活的人外周血淋巴细胞的c DNA基因库中用简并寡核苷酸探针克隆出的一编码基因... 详细信息

尼克酰胺磷酸核糖转移酶（nicotinamide phosphoribosyltransferase,Nampt）最初称为前B细胞克隆增强因子（preB-cell colony-enhancing factor,PBEF）,是从激活的人外周血淋巴细胞的c DNA基因库中用简并寡核苷酸探针克隆出的一编码基因,在干细胞因子和白细胞介素7辅助参与时能够使前B细胞更加顺利的分化与成熟[1]。

关键词：消化系统肿瘤 Nampt nicotinamide 寡核苷酸探针细胞克隆尼克酰胺细胞分化编码基因口腔鳞状细胞癌白细胞介素

Association between NNMT gene polymorphism and nonalcoholic steatohepatitis

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China Medical Abstracts(Internal Medicine) 2014年第1期31卷 41-42页

作者：肖建新 Dept Gastroenterol No. 118 HospPLA

Objective To investigate the association between nicotinamide N-methyltransferase(NNMT)gene rs694539 variant and non-alcoholic steatohepatitis(NASH).Methods A total of 76 NASH patients who visited or were hospitalized in our hospital from January2010 to June 2013,as well as 160 healthy volunteers matched with the patients for Face,age,and sex,

关键词： NASH alcoholic nicotinamide matched visited aspartate alanine genotype protective cholesterol

INGAP、NIC和Vit D3体外诱导大鼠PDESC分化形成胰岛β细胞的研究

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INGAP、NIC和Vit D3体外诱导大鼠PDESC分化形成胰岛β细胞的研究

作者： Muhammad Waseem 广东海洋大学

学位级别：硕士

体外分化的胰岛素分泌细胞是糖尿病细胞治疗希望的来源。成体干细胞存在于胎儿胰腺导管组织中,并持续存在于成人胰管中,胰腺导管干细胞是胰腺内分泌祖细胞。胰岛细胞是在胰腺导管网络的发育过程中由上皮中发现的多能和双能祖细胞形成的... 详细信息

体外分化的胰岛素分泌细胞是糖尿病细胞治疗希望的来源。成体干细胞存在于胎儿胰腺导管组织中,并持续存在于成人胰管中,胰腺导管干细胞是胰腺内分泌祖细胞。胰岛细胞是在胰腺导管网络的发育过程中由上皮中发现的多能和双能祖细胞形成的。许多研究已经证实在成人胰腺的胰管中存在双能干细胞/祖细胞。此外,谱系追踪研究表明,这些祖细胞在胰腺损伤或应激时可产生新β细胞。许多研究人员使用胰腺导管干/祖细胞进行β样细胞的体外发育,该细胞可作为糖尿病患者的β细胞替代来源,因为它们在经典动物模型中具有胰腺内分泌细胞再生的潜力。然而,β细胞的体外发育需要复制其发育的信号通路,这是一项艰巨的任务。因此,体外产生的β样细胞不够成熟,直到最近才用作β细胞替代的临床选择。尽管如此,由于单细胞RNA测序等新的生物技术出现,30年来关于β样细胞体外发育的研究接近尾声,这帮助我们了解了内分泌细胞发育中所涉及的细胞过程。本实验室已从大鼠胰腺导管组织分离培养一例胰腺导管干细胞系(PDESCs),并对其形态学特征、蛋白表达特性、细胞核型、多向分化性等进行了研究。本研究在已有大鼠胰腺导管干细胞系的基础上,分别比较在基础培养液中添加不同浓度INGAP-PP、Vit D3和NIC诱导大鼠胰腺导管干细胞分化形成胰岛β细胞的效果。筛选INGAP-PP、Vit D3和NIC的诱导浓度;以INGAP-PP、Vit D3和NIC最佳诱导浓度随机组合建立诱导方案,比较不同方案诱导大鼠胰腺导管干细胞分化形成胰岛β细胞的效果。我们分析了不同诱导组组的细胞形态、相关转录因子的基因表达以及糖刺激胰岛素分泌(GSIS),以比较不同因子单独和组合对PDSC分化为β样细胞的影响。本研究分为四个部分:试验1:INGAP-PP体外诱导大鼠胰腺导管干细胞分化形成胰岛β细胞本研究旨在比较基础培养液中添加不同浓度INGAP-PP对诱导大鼠胰腺导管干细胞分化形成胰岛β细胞的影响。培养并扩增第12代PDESC,以1×10细胞/孔接种到12孔板中。不同的试验组包括,一个对照组和四个INGAP-PP诱导组,每个组有36个重复。其中包括一个对照组和四个INGAP-PP诱导组。以(DMEM/F12+10%FBS+1%青霉素-链霉素)为基础培养液,诱导组分别在基础培养液的基础上添加100n M、150n M、200n M和250n M的INGAP-PP。细胞在37℃,5%CO2培养箱中培养28天。在28天的诱导后,使用DTZ染色、q PCR、免疫荧光和GSIS检查诱导细胞的INS1和Pdx1 m RNA表达水平、胰岛素和Pdx1蛋白的细胞内表达以及胰岛素和C肽的分泌量。结果表明,INGAP诱导组的诱导细胞生长像具有DTZ染色阳性细胞的ICC,而对照组没有发展成胰岛β细胞。此外,INS1和Pdx1在INGAP补充组中的m RNA表达明显高于对照组(p<0.01),ICC中的诱导细胞显示胰岛素和Pdx1共同表达。当INGAP诱导组的诱导细胞暴露在低糖和高糖下时,它们分泌的胰岛素和C肽水平显著高于对照组(p<0.01)。上述试验结果表明,150n M INGAP-PP能够有效地诱导PDESC分化成胰岛素分泌β样细胞。该组细胞团的大小大于其他诱导组,胰岛素、Pdx1 m RNA和蛋白质的表达也很高,诱导的ICC在低糖和高糖条件下分泌更多的胰岛素和C-肽。试验2:NIC体外诱导大鼠胰腺导管干细胞分化形成胰岛β细胞这项研究的目的是确定将成年大鼠PDESC分化成β样细胞的最佳NIC浓度。在这个实验中,取12代大鼠胰腺导管干细胞,按1×10个/孔接种于12孔板中。总共接种15个12孔板,分别设置对照组和4个不同浓度NIC诱导试验组,每组3个12孔板,共36个重复孔。对于对照组,基础培养液(DMEM/F12+10%FBS+1%青霉素-链霉素)被用作诱导液,而对于四个NIC诱导组,分别在基础培养液的基础上添加5m M,10m M,15m M和20m M的NIC。PDESC在37℃,5%CO2培养箱中培养28天,每三天用显微镜观察细胞的形态变化。DTZ染色、q PCR、免疫荧光和糖刺激试验分别用于识别诱导细胞INS1和Pdx1表达水平、细胞内胰岛素和Pdx1蛋白表达水平,结果显示,在28天诱导后释放胰岛素和C-肽。NIC诱导组的诱导细胞生长像胰岛素分泌细胞与DTZ染色阳性细胞,而对照组没有形成胰岛素分泌细胞。此外,NIC诱导组的INS1和Pdx1 m RNA表达率明显高于对照组(p<0.01),诱导组中的细胞具有胰岛素和Pdx1共同表达。当NIC补充组的诱导细胞受到低和高血糖浓度的影响时,它们分泌的胰岛素和C-肽(p<0.01)明显多于对照组的胰岛素和C-肽释放量。这些结果表明,NIC可以诱导大鼠胰腺导管干细胞分化为β细胞,并且添加10m M NIC时诱导效果最佳。试验3:Vit D3体外诱导大鼠胰腺导管干细胞分化形成胰岛β细胞本研究旨在比较基础培养液

关键词：胰腺导管干细胞 β细胞 INGAP-PP nicotinamide Vitamin D3 大鼠

尼克刹米及其代谢产物的气相色谱/质谱法分析

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中国法医学杂志 1991年第2期6卷 87-89页

作者：侯一斌黑龙江省公安厅哈尔滨市150001

尼克刹米(即可拉明)为中枢兴奋药物,属于滥用药物之列,也是体育比赛的违禁药物。因此,血和尿中尼克刹米的检验在法庭科学和医学领域中都很有意义。Shaev 和 Seme-nov 报导了用气相色谱法检验运动员尿中的尼克刹米等兴奋剂。但是,由于尼... 详细信息

尼克刹米(即可拉明)为中枢兴奋药物,属于滥用药物之列,也是体育比赛的违禁药物。因此,血和尿中尼克刹米的检验在法庭科学和医学领域中都很有意义。Shaev 和 Seme-nov 报导了用气相色谱法检验运动员尿中的尼克刹米等兴奋剂。但是,由于尼克刹米在体内代谢迅速其代谢产物的检验更有实际价值。

关键词： Nikethamide nicotinamide Metabolite GC/MS

NAMPT as a therapeutic target against stroke

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中国药理学通报 2015年第B11期31卷 169-169页

作者： MIAOChao-yu DepartmentofPharmacology SecondMilitaryMedicalUniversityShanghai200433

Aim nicotinamide phosphoribosyltransferase （NAMPT）, also an adipokine known as visfatin, acts via enzymatic activity to synthesize nicotinamide mononucleotide （NMN） and then maintain homeostasis of nicotinam- ide adenine dinucleotide （NAD）, which plays a dual role in energy metabolism and biological signaling. Of note, the NAMPT metabolic pathway connects NAD-dependent sirtuin signaling, constituting a strong intrinsic defense system against various stresses. Most recently, we and others have demonstrated several mechanisms by which NAMPT might serve as a therapeutic target against ischemic stroke, including cerebroprotection in the acute phase as well as vascular repair and neurogenesis in the chronic phase. The molecular mechanisms underlying these bene- fits have been explored in vivo and in vitro for neural cells, endothelial progenitor cells, and neural stem cells. Therapeutic interventions using NMN, NAMPT activators and ischemic conditioning are promising for stroke salvage and rehabilitation. Here, we discuss the current NAMPT data in the context of translational efforts for stroke treat- ment.

关键词： stroke therapeutic targets NAMPT adipokines nicotinamide mononucleotide NAD

Histochemical Localization of Nitric Oxide Synthase Positive Nerves in Chicken Oviduct

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畜牧与兽医 2012年第S1期44卷 341-341页

作者： Yang Ping Jameel Ahmed Gandahi Zhang Linli Zhang Qian Chen Qiusheng College of Veterinary Medicine in Nanjing Agricultural University

Nitric oxide(NO)is an important inhibitory neurotransmitter,synthesized by the enzyme nitric oxide synthase(NOS)locally in many tissues.The histochemical technique using nicotinamide adenine dinucleotide-diaphorase/nitric oxide synthase(NADPH-d/NOS)is often employed to determine the presence of this enzyme in the neuronal as well as other cell populations.We

关键词： Synthase populations dinucleotide neuronal nicotinamide histochemical adenine NADPH varied locally

Contribution of oxidative stress to pulmonary arterial hypertension

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World Journal of Cardiology 2010年第10期2卷 316-324页

作者： Vincent G DeMarco Adam T Whaley-Connell James R Sowers Javad Habibi Kevin C Dellsperger Department of Internal Medicine University of Missouri School of Medicine Diabetes and Cardiovascular Laboratory University of Missouri School of Medicine Department of Medical Pharmacology and Physiology University of Missouri School of Medicine Harry S Truman Veterans Affair Medical Center

Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen species (ROS), altered redox state, and elevated oxidant stress have been demonstrated in the lungs and RV of several animal models of PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, and the transgenic Ren2 rat which overexpresses the mouse renin gene. Generation of ROS in these models is derived mostly from the activities of the nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase. As disease progresses circulating monocytes and bone marrow-derived monocytic progenitor cells are attracted to and accumulate in the pulmonary vasculature. Once established, these inflammatory cells generate ROS and secrete mitogenic and fibrogenic cytokines that induce cell proliferation and fibrosis in the vascular wall resulting in progressive vascular remodeling. Deficiencies in antioxidant enzymes also contribute to pulmonary hypertensive states. Current therapies were developed to improve endothelial function, reduce pulmonary artery pressure, and slow the progression of vascular remodeling in the pulmonary vasculature by targeting deficiencies in either NO (PDE-type 5 inhibition) or PGI 2 (prostacyclin analogs), or excessive synthesis of ET-1 (ET receptor blockers) with the intent to improve patient clinical status and survival. New therapies may slow disease progression to some extent, but long term management has not been achieved and mortality is still high. Although little is known concerning the effects of current pulmonary arterial hypertension treatments on RV structure and function, interest in this area is increasing. Development of therapeutic strategies that simultaneously target pathology in the pulmonary vasculature and RV may be beneficial in reducing mortality associated with RV failure.

关键词： Pulmonary arterial hypertension Rosuvastatin Oxidative stress nicotinamide adenine dinucleotide phosphate oxidase Statins

THE CYTOGENOTOXIC EFFECTS OF OCCUPATIONAL EXPOSURE TO N,N^t-METHYLENE-BIS-(2-AMINO-1,3,4-THIADIAZOLE)

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癌变．畸变．突变 1991年第S1期3卷 67-67页

The study was designed to investigatecytogenotoxic effects of occupationalexposure to N,N’-methylene-bis-(2-amino-1,3,4-thiadiazole) (MATDA) for 11 workers(2 male,9 female) exposed to MATDA for 4-8 years,with the ave... 详细信息

关键词： exposed methylene exposure nicotinamide lymphocyte DNA fleet induction evidences

Oxidative and nitrosative stress enzymes in relation to nitrotyrosine in Helicobacter pylori-infected humans

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World Journal of Gastrointestinal Pathophysiology 2014年第3期5卷 373-379页

作者： Anders Elfvin Anders Edebo Peter Hallersund Anna Casselbrant Lars Fndriks Department of Gastrosurgical Research and Education Institute of Clinical Sciences Sahlgrenska Academy at University of Gothenburg Department of Pediatrics Institute of Clinical Sciences Sahlgrenska Academy at University of Gothenburg

AIM: To compare a possible relation between Helicobacter pylori(H. pylori) and the oxygen- and nitrogen radical system in humans. METHODS: Mechanisms for H. pylori to interfere with the oxygen and nitrogen radical system is of great importance for understanding of the H. pylori persistence and pathogenesis. Biopsies were obtained from the gastric wall of 21 individuals. Ongoing infection with H. pylori was detected using direct analyze from the biopsies using campylobacter-like organism test(CLO-test) and/or by using 14C-urea breath test. The individuals were divided in a negative H. pylori and a positive H. pylori group. Expression in the gastric mucosa of induc-ible nitric oxide syntase(iNOS), nicotinamide adenine dinucleotide phosphate-oxidase(NADPH-oxidase) myeloperoxidase(MPO), and nitrotyrosine were assessed by Western blotting.RESULTS: The individuals who undervent gastroscopy were divided in a H. pylori neg. [n = 13, m/f = 7/6, age(mean) = 39] and a H. pylori pos. group [n = 8, m/f = 5/3, age(mean) = 53]. Using western blot analysis iNOS was detected as a 130 kDa band. The iNOS expression was upregulated in the antrum of H. pylori infected individuals in comparison to the controls, mean ± SD being 12.6 ± 2.4 vs 8.3 ± 3.1, P < 0.01. There was a markedly upregulated expression of MPO in the antrum of H. pylori infected individuals in comparison to the control group without infection. In several of noninfected controls it was not possible to detect any MPO expression at all, whereas the expression was high in all the infected subjects, mean ± SD being 5.1 ± 3.4 vs 2.1 ± 1.9, P < 0.05. The NADPH-oxidase expression was analysed by detecting the NADPH-oxidase subunit p47-phox expression. P47-phox was detected as a 47 kDa band using Western blot, and showed a significantly higher expression of p47-phox in the antrum of the H. pylori infected individuals compared to the controls, mean ± SD being 3.1 ± 2.2 vs 0.3 ± 0.2, P < 0.01. Regarding nitrotyrosine formation, Western blot did not show any significant increase

关键词： Helicobacter pylori Radical Myeloperoxidase nicotinamide adenine dinucleotide phosphate Nitrotyrosine Gastric