Nicotinamide n-Oxide Attenuates HSV-1-Induced Microglial Inflammation through Sirtuin-1/NF-κB Signaling

HSV-1 is a typical neurotropic virus that infects the brain and causes keratitis, cold sores, and occasionally, acute herpes simplex encephalitis (HSE). The large amount of proinflammatory cytokines induced by HSV-1 infection is an important cause of neurotoxicity in the central nervous system (CNS). Microglia, as resident macrophages in CNS, are the first line of defense against neurotropic virus infection. Inhibiting the excessive production of inflammatory cytokines in overactivated microglia is a crucial strategy for the treatment of HSE. In the present study, we investigated the effect of nicotinamide n-oxide (NAMO), a metabolite mainly produced by gut microbe, on HSV-1-induced microglial inflammation and HSE. We found that NAMO significantly inhibits the production of cytokines induced by HSV-1 infection of microglia, such as IL-1β, IL-6, and TNF-α. In addition, NAMO promotes the transition of microglia from the pro-inflammatory M1 type to the anti-inflammatory M2 type. More detailed studies revealed that NAMO enhances the expression of Sirtuin-1 and its deacetylase enzymatic activity, which in turn deacetylates the p65 subunit to inhibit NF-κB signaling, resulting in reduced inflammatory response and ameliorated HSE pathology. Therefore, Sirtuin-1/NF-κB axis may be promising therapeutic targets against HSV-1 infection-related diseases including HSE.     

布洛芬-烟酰胺共晶制备及其溶解度测定

采用乙醇-水混合溶剂,对布洛芬-烟酰胺共晶的溶液结晶法制备过程进行了研究,制备样品的PXRD和DSC表征结果证明了通过溶液结晶法大规模制备布洛芬 烟酰胺共晶的可行性。制备过程研究结果表明,当混合溶剂中乙醇与水的体积配比为1.82～7.11时,可以制备出布洛芬-烟酰胺共晶;而且随着乙醇与水体积配比的增大,共晶收率呈现先增大再减小的趋势,当体积配比为2.76时,共晶收率达到最大值(76.31%)。还在不同温度下测定了布洛芬-烟酰胺共晶在不同体积配比乙醇-水混合溶剂中的溶解度,结果表明随着温度和乙醇体积比例的升高,布洛芬-烟酰胺共晶的溶解度增大,最后用 Apelblat方程对溶解度数据进行拟合。     

The Catalysis of NAD^＋ on Methanol Anode Oxidation Electrode for Direct Methanol Fuel Cell

A tentative idea of developing a liquid-catalytic system on methanol anode oxidation was proposed by analyzing the characteristics of methanol anode oxidation in direct methanol fuel cell. The kinetics of methanol oxidation at a glassy carbon electrode in the presence of nicotinamide adenine dinucleotide ( NAD^ ) was investigated. It is found that the current density of methanol oxidation increases greatly and the electrochemical reaction impedance reduces obviously in the presence of NAD^ compared with those in the adsenee of NAD^ . The catalytic activity of NAD^ is sensitive to temperature. When the temperature preponderates over 45℃, NAD^ is out of fuuction of catalysis for methanol oxidation, which is probably due to the denaturation of NAD^ at a relatively high temperature.     

Direct electrochemical regeneration of enzymatic cofactor 1,4‐NADH on a cathode composed of multi‐walled carbon nanotubes decorated with nickel nanoparticles

Multi‐walled carbon nanotubes (MWCNTs) were grown on a stainless steel mesh and decorated with nickel nanoparticles (Ni NPs). The developed Ni NP‐MWCNT material was then used as a cathode in an electrochemical batch reactor to electrocatalytically convert NAD⁺ to enzymatically‐active 1,4‐NADH. The regeneration of 1,4‐NADH was studied at various electrode potentials. At electrode potential of ?1.6 V, a very high recovery (relative amount of 1,4‐NADH in the product mixture) was obtained, 98 ± 1 %. In comparison, to achieve the same recovery on a non‐decorated MWCNT cathode, a much higher cathodic potential was needed (?2.3 V), establishing the importance of Ni NPs on the electrocatalytic activity in reducing NAD⁺ to 1,4‐NADH. It was postulated that hydrogen adsorbs on Ni NPs immobilized on MWCNTs to form Ni‐H_ads, and this activated hydrogen rapidly reacts with neighbouring NAD‐radicals, preventing the dimerization of the latter species, ultimately yielding 1,4‐NADH.     

Molecularly imprinted polymer for solid phase extraction of nicotinamide in pork liver samples

Aromatic polyamides and polythioamides with pendent chlorobenzylidine rings were synthesized through direct polycondenzation of 2‐(p‐chlorobenzalimino) terephthalic acid with the diamines 4,4′‐oxidianiline (1a), 4,4′‐methylenediamide (1b), 4,4′‐diaminodiphenyl sulfone (1c), and thioamines 4,4′‐(bisthiourea) diphenyl ether (3a), 4,4′‐(bisthiourea) diphenyl methane (3b), 4,4′‐(bisthiourea) diphenyl sulfone (3c), respectively, in DMF using P(OPh)₃/pyridine. The polymers were precipitated using water as nonsolvent. FTIR and ¹H‐NMR spectroscopic analysis was used to characterize the monomers and polymers. Representative polyamides and polythioamides were used for the removal of heavy metal ions such as Pb(II), Cd(II), Cu(II), and Cr(III) from aqueous solutions. The effects of pH, contact time, and initial concentration on the uptake of metal ions have been investigated. The adsorption capacities under competitive conditions were in the order Pb (II) > Cu (II) > Cr (III) > Cd (II). The adsorbed ions were eluted by treatment with 2N HCl, and the activities of the polymers are retained after fourth regeneration. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Involvement of the MetO/Msr System in Two Acer Species That Display Contrasting Characteristics during Germination

The levels of methionine sulfoxide (MetO) and the abundances of methionine sulfoxide reductases (Msrs) were reported as important for the desiccation tolerance of Acer seeds. To determine whether the MetO/Msrs system is related to reactive oxygen species (ROS) and involved in the regulation of germination in orthodox and recalcitrant seeds, Norway maple and sycamore were investigated. Changes in water content, MetO content, the abundance of MsrB1 and MsrB2 in relation to ROS content and the activity of reductases depending on nicotinamide adenine dinucleotides were monitored. Acer seeds differed in germination speed—substantially higher in sycamore—hydration dynamics, levels of hydrogen peroxide, superoxide anion radicals (O₂^•−) and hydroxyl radicals (•OH), which exhibited peaks at different stages of germination. The MetO level dynamically changed, particularly in sycamore embryonic axes, where it was positively correlated with the levels of O₂^•− and the abundance of MsrB1 and negatively with the levels of •OH and the abundance of MsrB2. The MsrB2 abundance increased upon sycamore germination; in contrast, it markedly decreased in Norway maple. We propose that the ROS–MetO–Msr redox system, allowing balanced Met redox homeostasis, participates in the germination process in sycamore, which is characterized by a much higher speed compared to Norway maple.     

Studies of the Binding of Modest Modulators of the Human Enzyme,Sirtuin 6, by STD NMR

Pyrazinamide (PZA), an essential constituent of short‐course tuberculosis chemotherapy, binds weakly but selectively to Sirtuin 6 (SIRT6). Despite the structural similarities between nicotinamide (NAM), PZA, and pyrazinoic acid (POA), these inhibitors modulate SIRT6 by different mechanisms and through different binding sites, as suggested by saturation transfer difference (STD) NMR. Available experimental evidence, such as that derived from crystal structures and kinetic experiments, has been of only limited utility in elucidation of the mechanistic details of sirtuin inhibition by NAM or other inhibitors. For instance, crystallographic structural analysis of sirtuin binding sites does not help us understand important differences in binding affinities among sirtuins or capture details of such dynamic process. Hence, STD NMR was utilized throughout this study. Our results not only agreed with the binding kinetics experiments but also gave a qualitative insight into the binding process. The data presented herein suggested some details about the geometry of the binding epitopes of the ligands in solution with the apo‐ and holoenzyme. Recognition that SIRT6 is affected selectively by PZA, an established clinical agent, suggests that the rational development of more potent and selective NAM surrogates might be possible. These derivatives might be accessible by employing the malleability of this scaffold to assist in the identification by STD NMR of the motifs that interact with the apo‐ and holoenzymes in solution.     

高效液相色谱法测定化妆品中烟酰胺的含量

建立了一种测定化妆品中烟酰胺的高效液相色谱方法。试验以质量分数0.1%甲酸水溶液-甲醇(体积比95∶5)为流动相,用C18色谱柱分离,流速为1.0mL/min,检测波长260nm,检测化妆品中的烟酰胺。结果显示烟酰胺线性范围为0.5~20mg/L,化妆品中定性检出限为0.50mg/kg,平均回收率为91.3%~109.4%。此方法样品处理简单,分析准确可靠,适用于对各类化妆水和护肤霜中烟酰胺的检测。同时对于阳性样品,建立了液相色谱-串联质谱的确证方法。     

天然烟酰胺辅因子再生体系及其人工类似物研究进展

氧化还原酶可以催化具有特定区域选择性、化学选择性、立体选择性的反应,反应条件温和且催化效率高,因此在有机化学和制药领域发挥着日益重要的作用。绝大多数氧化还原酶依赖烟酰胺腺嘌呤二核苷酸NAD（H）和烟酰胺腺嘌呤二核苷酸磷酸NADP（H）为酶促反应提供氧化还原当量。NAD（H）/NADP（H）由于价格昂贵、稳定性差导致无法化学计量投入。经过几十年研究,形成了4种经典的NAD（H）/NADP（H）再生方法：酶法、化学法、电化学法和光化学法,与此同时,一系列稳定性好、活性高且廉价的人工烟酰胺辅因子mNAD（H） s尤其是1,4-二氢吡啶类烟酰胺辅因子的开发和利用为NAD（H）/NADP（H）工业化运用提供了新的思路。     

新烟碱类农药中间体乙酰基恶二嗪的合成

对农药重要中间体乙酰基-4-硝基亚氨基-1,3,5-恶二嗪的合成进行了研究,探讨了溶剂、时间、温度、物料配比等因素对反应收率的影响。最佳反应条件为1mol4-硝基亚氨基-1,3,5-恶二嗪与1.2mol乙酰氯以DMF为溶剂、在5℃～10℃下反应10h,收率80％。并得到了与文献报道理化性质完全不同的产物,结构经IR、^1HNMR和元素分析确证.