Inverse correlation between the expression of AMPK/SIRT1 and NAMPT in psoriatic skin: A pilot study

PurposeEpidermal hyperplasia and the involvement of immune cells characterize the clinical picture of psoriasis. Among the several factors involved, attention has been focused on sirtuin 1 (SIRT1) - a deacetylase endowed with a variety of functions including the control of metabolic and inflammatory processes-, and on nicotinamide phosphoribosyltransferase (NAMPT), important for SIRT1 activation and involved in inflammatory events. The aim of the study was to analyze changes of SIRT1 and NAMPT expression in psoriatic skin.Patients and methodsSamples from healthy controls and psoriatic patients were subjected to immunohistochemical analysis.ResultsA strong downregulation of SIRT1 expression was observed in skin samples from psoriatic patients compared to healthy controls. This was accompanied by a parallel reduction of adenosine monophosphate-activated kinase (AMPK) expression and, more strikingly, by the disappearance of cells immunolabeled for its active, phosphorylated form (pAMPK). In both cases, analysis of the distribution of immunopositive cells revealed a shift towards reduced intensity of staining. In contrast, NAMPT expression was upregulated in psoriatic samples in line with its pro-inflammatory role. This was again more visible with an intensity-based distribution analysis that evidenced a shift towards more intensely immunostained cell populations.ConclusionsThe present data correlate in the same samples the expression of SIRT1, pAMPK/AMPK and NAMPT in psoriasis and open the way for novel pharmacological targets in the treatment of the disease.     

Adipokines in dental pulp: Physiological,pathological, and potential therapeutic roles

BackgroundHundreds of adipokines have been identified, and their extensive range of endocrine functions—regulating distant organs such as oral tissues—and local autocrine/paracrine roles have been studied. In dentistry, however, adipokines are poorly known proteins in the dental pulp; few of them have been studied despite their large number. This study reviews recent advances in the investigation of dental-pulp adipokines, with an emphasis on their roles in inflammatory processes and their potential therapeutic applications.HighlightsThe most recently identified adipokines in dental pulp include leptin, adiponectin, resistin, ghrelin, oncostatin, chemerin, and visfatin. They have numerous physiological and pathological functions in the pulp tissue: they are closely related to pulp inflammatory mechanisms and actively participate in cell differentiation, mineralization, angiogenesis, and immune-system modulation.ConclusionAdipokines have potential clinical applications in regenerative endodontics and as biomarkers or targets for the pharmacological management of inflammatory and degenerative processes in dental pulp. A promising direction for the development of new therapies may be the use of agonists/antagonists to modulate the expression of the most studied adipokines.     

Treatment of Lesch–Nyhan disease with S-adenosylmethionine: Experience with five young Malaysians,including a girl

Background: Lesch–Nyhan disease (LND) is a rare X-linked recessive neurogenetic disorder caused by deficiency of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT, EC 2.4.2.8) which is responsible for recycling purine bases into purine nucleotides. Affected individuals have hyperuricemia leading to gout and urolithiasis, accompanied by a characteristic severe neurobehavioural phenotype with compulsive self-mutilation, extrapyramidal motor disturbances and cognitive impairment. Aim: For its theoretical therapeutic potential to replenish the brain purine nucleotide pool, oral supplementation with S-adenosylmethionine (SAMe) was trialed in 5 Malaysian children with LND, comprising 4 related Malay children from 2 families, including an LND girl, and a Chinese Malaysian boy. Results: Dramatic reductions of self-injury and aggressive behaviour, as well as a milder reduction of dystonia, were observed in all 5 patients. Other LND neurological symptoms did not improve during SAMe therapy. Discussion: Molecular mechanisms proposed for LND neuropathology include GTP depletion in the brain leading to impaired dopamine synthesis, dysfunction of G-protein-mediated signal transduction, and defective developmental programming of dopamine neurons. The improvement of our LND patients on SAMe, particularly the hallmark self-injurious behaviour, echoed clinical progress reported with another purine nucleotide depletion disorder, Arts Syndrome, but contrasted lack of benefit with the purine disorder adenylosuccinate lyase deficiency. This first report of a trial of SAMe therapy in LND children showed remarkably encouraging results that warrant larger studies.     

尼克酰胺磷酸核糖转移酶对心肌缺血/再灌注的影响研究进展

背景 尼克酰胺磷酸核糖转移酶(nicotinamide phosphoribosyltransferase,NAMPT)是合成烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD)的限速酶.NAMPT可存在于细胞内和细胞外,它们的作用不尽相同.NAMPT在心血管系统中发挥着重要作用,但在心肌缺血/再灌注(ischemia/reperfusion,I/R)中的作用尚存争议. 目的 进一步了解NAMPT的心血管作用及对心肌I/R的影响. 内容 就目前研究对NAMPT的来源及潜在的心血管作用、细胞内NAMPT(intracellular NAMPT,iNAMPT)及细胞外NAMPT(extracellular NAMPT,eNAMPT)、以及对心肌I/R的影响作一综述. 趋向 促进对NAMPT的作用及机制的了解,NAMPT有望成为治疗心肌I/R损伤的新靶点.     

The biology,function, and applications of exosomes in cancer

Exosomes are cell-derived nanovesicles with diameters from 30 to 150 nm, released upon fusion of multivesicular bodies with the cell surface. They can transport nucleic acids, proteins, and lipids for intercellular communication and activate signaling pathways in target cells. In cancers, exosomes may participate in growth and metastasis of tumors by regulating the immune response, blocking the epithelial–mesenchymal transition, and promoting angiogenesis. They are also involved in the development of resistance to chemotherapeutic drugs. Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers. Because of their amphipathic structure, exosomes are natural drug delivery vehicles for cancer therapy.     

The relationship between circulating visfatin/nicotinamide phosphoribosyltransferase,obesity, inflammation and lipids profile in elderly population,determined by structural equation modeling

Background: The available literature suggests that circulating visfatin/Nicotinamide Phosphoribosyltransferase (NAMPT) level variability in humans is related to obesity, insulin resistance, inflammation, and lipid profile. The aim of the study was to assess the relationship between circulating visfatin/NAMPT, obesity, insulin resistance, inflammation, and lipid profile in a large population-based, elderly cohort, applying structural equation modeling.

Materials and methods: The analysis included 2983 elderly participants of the PolSenior study with assessed total blood count, fasting concentrations of lipids, glucose, insulin, hs-CRP, interleukin-6, and visfatin/NAMPT (by ELISA), and calculated HOMA-IR.

Results: The circulating visfatin/NAMPT levels were higher in obese compared to normal weight subjects, in those with hs-CRP above 3?mg/L, with low serum HDL cholesterol, and in insulin resistant subjects. Based on results of the exploratory factor analysis, a baseline model of mutual relationship between four latent and measured variables was created and a final model was developed by maintaining only two significant categories. The important variables for ‘latent inflammation’ proved to be hs-CRP and IL-6 serum levels. In the case of ‘nutritional status’, important variables were BMI, waist circumference, and to a lesser extent insulin resistance. Additionally, the residual correlation between those two constructs was also statistically significant.

Conclusion: The structural equation modeling provided support for the existence of a link between nutritional status, inflammation and circulating visfatin/NAMPT level. This indicates that circulating visfatin/NAMPT can be considered as a novel surrogate marker of systemic inflammation associated with fat depot, especially visceral, in the elderly population.     

Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis

Adult neurogenesis is the process of generating new neurons throughout life in the olfactory bulb and hippocampus of most mammalian species, which is closely related to aging and disease. Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, is the rate‐limiting enzyme for mammalian nicotinamide adenine dinucleotide (NAD) salvage synthesis by generating nicotinamide mononucleotide (NMN) from nicotinamide. Recent findings from our laboratory and other laboratories have provided much evidence that NAMPT might serve as a therapeutic target to restore adult neurogenesis. NAMPT‐mediated NAD biosynthesis in neural stem/progenitor cells is important for their proliferation, self‐renewal, and formation of oligodendrocytes in vivo and in vitro. Therapeutic interventions by the administration of NMN, NAD, or recombinant NAMPT are effective for restoring adult neurogenesis in several neurological diseases. We summarize adult neurogenesis in aging, ischemic stroke, traumatic brain injury, and neurodegenerative disease and review the advances of targeting NAMPT in restoring neurogenesis. Specifically, we provide emphasis on the P7C3 family, a class of proneurogenic compounds that are potential NAMPT activators, which might shed light on future drug development in neurogenesis restoration.     

日本血吸虫HGPRT编码基因的克隆与表达

目的 克隆和表达日本血吸虫大陆株次黄嘌呤鸟嘌呤磷酸核糖转移酶(HGPRT)编码基因。方法依据GenBank日本血吸虫HGPRT开放阅读框(ORF)设计一对引物，上游和下游引物分别引入BamH I和Sal I酶切位点。以日本血吸虫大陆株（安徽株，简称Sjc-A）成虫总RNA为模板，反转录PCR (RT-PCR)扩增日本血吸虫大陆株HGPRT(SjcHGPRT)全长编码基因。经双酶切纯化的PCR产物与同样双酶切纯化的pET28a质粒DNA片段用T4 DNA连接酶连接，构建重组质粒pET28a-SjcHGPRT，转化感受态E．coli BL21，并大量扩增。重组质粒DNA经限制性内切酶双酶切、PCR、琼脂糖凝胶电泳和核苷酸序列测定进行鉴定。pET28a-SjcHGPRT/E．coli BL21I程菌用IPTG诱导表达，重组蛋白用SDS-PAGE和Western blot分析。结果 SjcHGPRT编码基因RT-PCR产物约700 bp，构建的pET28a-SjcHGPRT重组质粒DNA经限制性内切酶双酶切和PCR扩增产物于琼脂糖凝胶电泳均观察到相同大小的基因片段，根据核苷酸序列测序结果推导的氨基酸序列与报道的日本血吸虫大陆株（湖南株，简称Sjc-H）及曼氏血吸虫HGPRT分别有99%和83%的同源性。获得的重组蛋白(reSjcHGPRT)经SDS-PAGE和Western blot分析，分子量约30 kDa，并能被抗His-G-HRP抗体、日本血吸虫感染小鼠血清和日本血吸虫病人血清识别。结论 日本血吸虫大陆株(安徽株)HGPRT表达获得成功，并获得了纯化重组蛋白，为开展该分子功能和免疫原性研究奠定了基础。     

内脂素/前B细胞克隆增强因子与妊娠

内脂素/前B细胞克隆增强因子（visfatin/PBEF）作为新发现的脂肪因子,主要在内脏脂肪和大网膜中表达,具有类胰岛素作用、参与炎症反应和免疫调节等功能。妊娠期妇女处于特殊的生理状态,能量代谢发生特征性改变。最新观点认为妊娠合并症,如妊娠期糖尿病和妊娠期高血压疾病均存在胰岛素抵抗,是妊娠妇女体内代谢功能紊乱所致。近年对visfatin/PBEF的结构和功能、其与代谢综合征、子痫前期、妊娠期糖尿病和胎儿生长受限关系的研究提示,visfatin/PBEF可能参与妊娠相关疾病的发生和发展。就近年关于vis-fatin/PBEF和妊娠合并症的相关研究综述。     

内脂素与子痫前期

内脂素(visfatin)是新近发现的一种主要由内脏脂肪细胞分泌的脂肪因子,结构复杂,存在基因多态性,具有调节糖脂代谢作用.内脂索增加胰岛素敏感性、促进血管平滑肌细胞成熟、参与炎症反应及血管生成,与动脉粥样硬化形成及血管内皮细胞受损和功能紊乱密切相关.子痫前期是一种病因不明的病理妊娠,严重危害母要生命,血管内皮细胞损伤...