• 【Gordonia sp。中脂质积累和体内酯形成的生理学表征。 KTR9。】 复制标题 收藏 收藏
    DOI:10.1007/s10295-012-1218-6 复制DOI
    作者列表:Eberly JO,Ringelberg DB,Indest KJ
    BACKGROUND & AIMS: :Previous work has demonstrated the feasibility of in vivo biodiesel synthesis in Escherichia coli, however, ethyl ester formation was dependent on an external fatty acid feedstock. In contrast to E. coli, actinomycetes may be ideal organisms for direct biodiesel synthesis because of their capacity to synthesize high levels of triacylglcerides (TAGs). In this study, we investigated the physiology and associated TAG accumulation along with the in vivo ability to catalyze ester formation from exogenous short chain alcohol sources in Gordonia sp. KTR9, a strain that possesses a large number of genes dedicated to fatty acid and lipid biosynthesis. Total lipid fatty acids content increased by 75 % and TAG content increased by 50 % under nitrogen starvation conditions in strain KTR9. Strain KTR9 tolerated the exogenous addition of up to 4 % methanol, 4 % ethanol and 2 % propanol in the media. Increasing alcohol concentrations resulted in a decrease in the degree of saturation of recovered fatty acid alcohol esters and a slight increase in the fatty acid chain length. A linear dose dependency in fatty alcohol ester synthesis was observed in the presence of 0.5-2 % methanol and ethanol compared to control KTR9 strains grown in the absence of alcohols. An inspection of the KTR9 genome revealed the presence of several putative wax ester synthase/acyl-coenzyme A : diacylglycerol acyltransferase (WS/DGAT) enzymes, encoded by atf gene homologs, that may catalyze the in vivo synthesis of fatty acid esters from short chain alcohols. Collectively, these results indicate that Gordonia sp. KTR9 may be a suitable actinomycete host strain for in vivo biodiesel synthesis.
    背景与目标: :先前的工作证明了在大肠杆菌中体内生物柴油合成的可行性,但是,乙酯的形成取决于外部脂肪酸原料。与大肠杆菌相反,放线菌可能是直接生物柴油合成的理想生物,因为它们能够合成高含量的三酰基甘油(TAGs)。在这项研究中,我们调查了生理和相关的TAG积累以及体内催化Gordonia sp。中外源短链醇源形成酯的能力。 KTR9,具有大量致力于脂肪酸和脂质生物合成的基因的菌株。在氮饥饿条件下,菌株KTR9的总脂质脂肪酸含量增加了75%,TAG含量增加了50%。菌株KTR9耐受培养基中外源添加多达4%的甲醇,4%的乙醇和2%的丙醇。醇浓度的增加导致回收的脂肪酸醇酯的饱和度降低,并且脂肪酸链长度略微增加。与在不存在醇的情况下生长的对照KTR9菌株相比,在存在0.5-2%的甲醇和乙醇的条件下观察到脂肪醇酯合成的线性剂量依赖性。对KTR9基因组的检查表明存在几种假定的蜡酯合酶/酰基辅酶A:二酰基甘油酰基转移酶(WS / DGAT)酶,这些酶由atf基因同源物编码,可能催化体内短链脂肪酸酯的合成酒精。总的来说,这些结果表明Gordonia sp。 KTR9可能是适合体内生物柴油合成的放线菌宿主菌株。
  • 【基于多孔二氧化硅纳米粒子的难溶性水飞蓟宾的72小时释放制剂:比格犬的体外释放动力学和体内/体外相关性。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejps.2012.10.012 复制DOI
    作者列表:Cao X,Deng W,Fu M,Zhu Y,Liu H,Wang L,Zeng J,Wei Y,Xu X,Yu J
    BACKGROUND & AIMS: :The objective of this study was to prepare a 72 h-release formulation of silybin (72 h-SLB) using a combination of solid dispersion, gel matrix and porous silica nanoparticles (PSNs) and to investigate the in vitro/in vivo correlations (IVIVCs). The results of scanning electron microscopy and N(2) adsorption demonstrated that empty PSNs possessed a spherical shape, a highly porous structure, a large specific surface area (385.89 ± 1.12 m(2)/g) and a small pore size (2.74 nm on average). The in vitro dissolution profiles of both 72 h-SLB and silybin-loaded PSNs in different concentrations (0.01, 0.06 and 0.08M) of Na(2)CO(3) solutions revealed that 0.06 M Na(2)CO(3) solution was the optimal medium in which silybin could be released from 72 h-SLB with first-order release kinetics and from PSNs with Higuchi kinetics. Furthermore, the IVIVCs of 72 h-SLB and silybin-loaded PSNs in beagle dogs were also established. Using 0.06 M Na(2)CO(3) solution as the in vitro dissolution medium, a good linear relationship could be achieved for both 72 h-SLB and silybin-loaded PSNs. The findings support the fact that the 72 h-SLB (consisting of solid dispersion, regular gel matrix and PSNs) together with Na(2)CO(3) solution as an in vitro dissolution medium can be developed into a promising formulation for poorly soluble drugs, which enjoys a good IVIVC.
    背景与目标: :这项研究的目的是使用固体分散体,凝胶基质和多孔二氧化硅纳米粒子(PSN)的组合制备水飞蓟宾(72 h-SLB)的72 h释放制剂,并研究体内/体外相关性( IVIVC)。扫描电子显微镜和N(2)吸附的结果表明,空的PSN具有球形,高度多孔的结构,较大的比表面积(385.89±1.12 m(2)/ g)和较小的孔径(2.74 nm)一般)。 Nah(2)CO(3)解决方案中不同浓度(0.01、0.06和0.08M)的72 h-SLB和水飞蓟宾加载的PSNs的体外溶出曲线显示0.06 M Na(2)CO(3)解决方案是最佳的培养基,其中水飞蓟宾可以从72 h-SLB中以一级释放动力学释放,而从PSN中以Higuchi动力学释放。此外,还建立了比格犬中72 h-SLB和水飞蓟宾的PSN的IVIVC。使用0.06 M Na(2)CO(3)解决方案作为体外溶出介质,可以为72 h-SLB和水飞蓟宾加载的PSNs都实现良好的线性关系。这些发现支持以下事实:72 h-SLB(由固体分散体,规则的凝胶基质和PSN组成)与Na(2)CO(3)解决方案一起作为体外溶出介质,可以开发为溶解性较差的有前途的制剂药物,享有良好的IVIVC。
  • 【在玉米芯酸水解产物和大豆油的混合培养基中,由Trichosporon dermatis组合进行“从头”和“从头”脂质发酵。】 复制标题 收藏 收藏
    DOI:10.1186/s13068-017-0835-8 复制DOI
    作者列表:Huang C,Luo MT,Chen XF,Qi GX,Xiong L,Lin XQ,Wang C,Li HL,Chen XD
    BACKGROUND & AIMS: BACKGROUND:Microbial oil is one important bio-product for its important function in energy, chemical, and food industry. Finding suitable substrates is one key issue for its industrial application. Both hydrophilic and hydrophobic substrates can be utilized by oleaginous microorganisms with two different bio-pathways ("de novo" lipid fermentation and "ex novo" lipid fermentation). To date, most of the research on lipid fermentation has focused mainly on only one fermentation pathway and little work was carried out on both "de novo" and "ex novo" lipid fermentation simultaneously; thus, the advantages of both lipid fermentation cannot be fulfilled comprehensively. RESULTS:In this study, corncob acid hydrolysate with soybean oil was used as a mix-medium for combined "de novo" and "ex novo" lipid fermentation by oleaginous yeast Trichosporon dermatis. Both hydrophilic and hydrophobic substrates (sugars and soybean oil) in the medium can be utilized simultaneously and efficiently by T. dermatis. Different fermentation modes were compared and the batch mode was the most suitable for the combined fermentation. The influence of soybean oil concentration, inoculum size, and initial pH on the lipid fermentation was evaluated and 20 g/L soybean oil, 5% inoculum size, and initial pH 6.0 were suitable for this bioprocess. By this technology, the lipid composition of extracellular hydrophobic substrate (soybean oil) can be modified. Although adding emulsifier showed little beneficial effect on lipid production, it can modify the intracellular lipid composition of T. dermatis. CONCLUSIONS:The present study proves the potential and possibility of combined "de novo" and "ex novo" lipid fermentation. This technology can use hydrophilic and hydrophobic sustainable bio-resources to generate lipid feedstock for the production of biodiesel or other lipid-based chemical compounds and to treat some special wastes such as oil-containing wastewater.
    背景与目标: 背景:微生物油因其在能源,化工和食品工业中的重要作用而成为一种重要的生物产品。寻找合适的基材是其工业应用的关键问题之一。具有两种不同生物途径(“从头”脂质发酵和“从头”脂质发酵)的油脂性微生物均可利用亲水性和疏水性底物。迄今为止,大多数关于脂质发酵的研究主要集中在仅一种发酵途径上,并且很少同时进行“从头”和“从头”脂质发酵的工作。因此,不能同时实现两种脂质发酵的优点。
    结果:在这项研究中,玉米芯酸与大豆油的水解产物被用作混合培养基,用于油脂性酵母曲氏菌(Trichosporon dermatis)的“从头”和“从头”组合脂质发酵。皮肤癣菌可同时有效地利用培养基中的亲水性和疏水性底物(糖和大豆油)。比较了不同的发酵模式,分批模式最适合组合发酵。评估了豆油浓度,接种量和初始pH对脂质发酵的影响,并且20 g / L豆油,5%接种量和pH 6.0适于此生物工艺。通过该技术,可以修饰细胞外疏水性底物(大豆油)的脂质组成。尽管添加乳化剂对脂质的产生几乎没有有益作用,但它可以改变皮肤炎球菌的细胞内脂质组成。
    结论:本研究证明了“从头”和“从头”脂质发酵相结合的潜力和可能性。该技术可以利用亲水和疏水的可持续生物资源来生产脂质原料,以生产生物柴油或其他基于脂质的化合物,并处理某些特殊废物,例如含油废水。
  • 【叶绿体超微结构和膜脂质组成与菠菜,常春藤和云杉叶片获得的不同抗冻性程度的相关性。】 复制标题 收藏 收藏
    DOI:10.1016/S0176-1617(84)80015-2 复制DOI
    作者列表:Senser M,Beck E
    BACKGROUND & AIMS: :The leaves of «moderately hardy» (spinach), «very hardy» (ivy) and «extremely hardy» (spruce) plants [classification according to Levitt {1980)] show characteristic differences with respect to changes in membrane lipid composition and chloroplast ultrastructure which are correlated with the degree of the frost resistance achieved by each type of tissue during adaptation to sub-zero temperatures. Spinach leaves showed no increase in their total lipid content upon frost hardening. On the contrary, the amount of galactolipids decreased considerably, whereas that of phospholipids only slightly increased. No shift from the saturated palmitic acid to the three-fold unsaturated linolenic acid was observed. The membrane lipid content of ivy leaves and spruce needles increased to a similar extent during frost hardening. However, in contrast to spruce needles, a distinct preferential accumulation of the phospholipids was observed in ivy leaves, resulting in an increased PL/GL ratio. A considerable shift from saturated (palmitic) to unsaturated fatty acids was detected in both plants, due mainly to an increase in the proportion of linoleic acid in ivy and of linolenic acid in spruce. In spite of the considerable increase in lipid content, no increase in chloroplast number per cell could be detected in ivy leaves, although the length of the thylakoids was nearly doubled and the plastids appeared to be in a division stage: however, no real division could ever be observed. On the contrary, an increase in the number of chloroplasts and mitochondria was observed in spruce needles. Membrane augmentation became further evident by the many large invaginations of the chloroplast envelope formed when the frost-hardened leaves of ivy or spruce were exposed to sub-zero temperatures which they could just survive.
    背景与目标: :“中等硬度”(菠菜),“极度坚硬”(ivy)和“极度坚硬”(云杉)植物的叶子[根据Levitt(1980)分类)在膜脂成分和叶绿体变化方面表现出特征差异超微结构,与适应零度以下温度时每种组织的抗冻性程度有关。霜冻硬化后,菠菜叶的总脂质含量没有增加。相反,半乳糖脂的量显着减少,而磷脂的量仅略有增加。没有观察到从饱和的棕榈酸到三倍的不饱和亚麻酸的转变。在霜冻硬化过程中,常春藤叶和云杉针的膜脂含量增加了相似的程度。然而,与云杉针头相反,在常春藤叶中观察到磷脂的明显优先积累,从而导致PL / GL比增加。在这两种植物中均检测到从饱和(棕榈酸)到不饱和脂肪酸的显着变化,这主要是由于常春藤中亚油酸和云杉中亚麻酸的比例增加。尽管脂质含量显着增加,但常春藤叶中未检测到每细胞的叶绿体数量增加,尽管类囊体的长度几乎增加了一倍,质体似乎处于分裂阶段:但是,不能进行真正的分裂曾经被观察到。相反,在云杉针头中观察到叶绿体和线粒体数量增加。当常春藤或云杉的冻干叶子暴露于零度以下的温度下就可以生存时,叶绿体包膜的许多大的浸入使膜的增强变得更加明显。
  • 【胎球蛋白通过清除剂受体介导肝脏对带负电荷的纳米粒子的摄取。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijpharm.2006.08.025 复制DOI
    作者列表:Nagayama S,Ogawara K,Minato K,Fukuoka Y,Takakura Y,Hashida M,Higaki K,Kimura T
    BACKGROUND & AIMS: :We tried to evaluate the possible involvement of fetuin in the scavenger receptors (SRs)-mediated hepatic uptake of polystyrene nanospheres with the size of 50 nm (NS-50), which has surface negative charge (zeta potential=-21.8+/-2.3 mV). The liver perfusion studies in rats revealed that the hepatic uptake of NS-50 pre-coated with fetuin (NS-50-fetuin) was significantly inhibited by poly inosinic acid (poly I), a typical inhibitor of SRs, whereas that of plain NS-50 or NS-50 pre-coated with BSA (NS-50-BSA) was not. The uptake of NS-50-fetuin by cultured Kupffer cells was also significantly inhibited by poly I, and anti-class A scavenger receptors (SR-A) antibody, suggesting that fetuin on NS-50 mediated the recognition and internalization of NS-50 by Kupffer cells and at least SR-A would be responsible for the uptake. Taken that Western blot analysis confirmed that fetuin certainly adsorbed on the surface of NS-50 after the incubation of NS-50 with serum, the results obtained in the present study indicate that fetuin would be one of the serum proteins that were substantially involved in the hepatic uptake of NS-50 via SRs.
    背景与目标: :我们试图评估胎球蛋白可能参与清道夫受体(SRs)介导的肝脏吸收大小为50 nm(NS-50)的聚苯乙烯纳米球,该表面具有表面负电荷(ζ电位= -21.8 /-2.3 mV)。对大鼠肝脏的灌注研究表明,预涂胎球蛋白(NS-50-胎球蛋白)的NS-50的肝吸收被SR的典型抑制剂聚肌苷酸(poly I)显着抑制,而普通NS抑制了肝摄取未预涂BSA的-50或NS-50(NS-50-BSA)。聚I和抗A类清道夫受体(SR-A)抗体也显着抑制了培养的Kupffer细胞对NS-50-胎球蛋白的摄取,表明NS-50上的胎球蛋白介导了NS-50的识别和内在化。枯否细胞的吸收,至少由SR-A引起。认为Western印迹分析证实胎球蛋白在将血清与NS-50孵育后肯定吸附在NS-50的表面上,本研究获得的结果表明胎球蛋白将是实质性参与胎盘蛋白的血清蛋白之一。肝通过SRs吸收NS-50。
  • 【包括HDL及其脂质过氧化产物在内的氧化脂蛋白抑制THP-1人巨噬细胞分泌TNF-α。】 复制标题 收藏 收藏
    DOI:10.1016/s0891-5849(97)00061-0 复制DOI
    作者列表:Girona J,La Ville AE,Heras M,Olivé S,Masana L
    BACKGROUND & AIMS: It has been established that oxidized LDL (ox-LDL) modifies cytokine secretion by macrophages, for example, by reducing tumor necrosis factor alpha (TNF-(alpha) m-RNA. However, little is known about the effects of oxidized high density lipoprotein (ox-HDL). This study reports the effects of ox-HDL subfractions 2 and 3 (ox-HDL2, ox-HDL3) compared with that of ox-LDL and some products of oxidation (hydroperoxides and aldehydes) on the secretion of TNF-alpha from THP-1 human monocytes derived macrophages in vitro. HDL2, HDL3 and LDL were oxidized with 10 microM Cu++ for 12 h and/or 24 h. Native and oxidized HDL and LDL were incubated for 24 h with macrophages with or without LPS (10 ng/ml) after which TNF-alpha secretion was measured in the culture medium. Lipid hydroperoxides and apolar aldehydes were also incubated with the cells for 2 h following which the medium was replaced and TNF-alpha secretion measured after a further 22 h of incubation. An inhibition of TNF-alpha by ox-HDL2 (p < .05), ox-HDL3 (p < .05) and ox-LDL (p < .05) from THP-1 macrophages was observed in the presence and absence of LPS. This inhibition remained the same after incubation with ox-HDL 12 h and 24 h. Hydroperoxides of linoleic acid did not modify TNF-alpha secretion by cells while five out of eight aldehydes analyzed (2,4-heptadienal, hexanal, 2-nonenal, 2-octenal, 2,4-decadienal) inhibited TNF-alpha secretion (p < .05). These findings demonstrate that ox-HDL, and some of its lipid peroxidation products, plays a role in the modulation of the inflammatory response by macrophages as previously observed for ox-LDL.

    背景与目标: 已经确定氧化的LDL(ox-LDL)可以通过减少肿瘤坏死因子α(TNF-αm-RNA)来调节巨噬细胞的细胞因子分泌。但是,对氧化的高密度脂蛋白的作用知之甚少(ox-HDL)。这项研究报告了与ox-LDL和某些氧化产物(氢过氧化物和醛类)相比,ox-HDL亚组分2和3(ox-HDL2,ox-HDL3)对TNF分泌的影响THP-1人单核细胞衍生的α-α体外,将HDL2,HDL3和LDL用10 microM Cu氧化12 h和/或24 h,将天然和氧化的HDL和LDL与有或没有LPS的巨噬细胞孵育24 h (10 ng / ml),然后在培养基中测量TNF-α的分泌,脂质过氧化氢和非极性醛也与细胞一起孵育2小时,然后更换培养基,再过22 h后测量TNF-α的分泌ox-HDL2对TNF-α的抑制作用(p < .05),在存在和不存在LPS的情况下观察到THP-1巨噬细胞的ox-HDL3(p <.05)和ox-LDL(p <.05)。与ox-HDL孵育12小时和24小时后,这种抑制作用保持不变。亚油酸的氢过氧化物不会改变细胞的TNF-α分泌,而分析的八种醛中的五种(2,4-庚二烯醛,己醛,2-壬烯醛,2-辛烯醛,2,4-癸二烯醛)抑制TNF-α分泌(p <.05)。这些发现表明,ox-HDL及其某些脂质过氧化产物在巨噬细胞对炎症反应的调节中起着作用,正如以前对ox-LDL所观察到的一样。

  • 【有机锡和有机铅化合物与模型脂质膜的疏水和亲水相互作用的作用。】 复制标题 收藏 收藏
    DOI:10.1515/znc-1997-3-412 复制DOI
    作者列表:Gabrielska J,Sarapuk J,Przestalski S
    BACKGROUND & AIMS: The present study was conducted to clarify the mechanism of toxicity of organic compounds using lipid model membranes (liposomes and planar lipid membranes). The compounds studied were trialkyltin and trialkyllead chlorides, dialkyltin dichlorides and some inorganic forms of those metals. Two different (anionic and cationic) detergents were also used in the experiments to change the surface properties of liposomes. As a measure of interaction between the compounds studied and model membranes were the release of liposome bound praseodymium and the change in stability of planar membranes under the influence of those compounds. On the basis of the results obtained it was postulated that the mechanism of interaction between tin- and leadorganics and model lipid membranes is a combination of different factors featuring interacting sides. The most important properties determining the behaviour of organic compounds in the interaction were lipophilicity and polarity of different parts of the organics and the steric arrangement they can take in the medium. On the other hand, the surface potential of the lipid bilayer and the environment of the lipid molecules, that play a significant role in the availability of the lipid bilayer to the organics, were important factors in the interaction.

    背景与目标: 进行本研究以阐明使用脂质模型膜(脂质体和平面脂质膜)的有机化合物的毒性机理。所研究的化合物为三烷基锡和三烷基氯化铅,二烷基二氯化锡和这些金属的某些无机形式。实验中还使用了两种不同的(阴离子和阳离子)去污剂来改变脂质体的表面性质。脂质体结合的ody的释放以及在这些化合物的影响下平面膜稳定性的变化是衡量所研究化合物与模型膜之间相互作用的一种量度。根据获得的结果,假设锡和铅有机物与模型脂质膜之间的相互作用机理是具有相互作用侧的不同因素的组合。决定有机化合物在相互作用中的行为的最重要特性是亲脂性和有机物不同部分的极性以及它们在介质中可采取的空间排列。另一方面,脂质双层的表面电势和脂质分子的环境在脂质双层对有机物的利用中起着重要作用,是相互作用的重要因素。

  • 【埃西替米贝被添加到艾滋病毒患者的最大耐受性降脂治疗中时是有效的。】 复制标题 收藏 收藏
    DOI:10.1186/1476-511X-6-15 复制DOI
    作者列表:Bennett MT,Johns KW,Bondy GP
    BACKGROUND & AIMS: :To determine the efficacy and safety of adding ezetimibe to maximally tolerated lipid lowering therapy in patients with HIV dyslipidemia. Retrospective analysis of lipid parameters was conducted for 33 patients with HIV who had been prescribed ezetimibe 10 mg per day. Mean total cholesterol was reduced 21% (p < 0.001). Mean LDL was reduced 35% (p < 0.001). Mean HDL increased 8% (p = 0.038). Mean triglyceride was reduced 34% (p = 0.006). Mean Apolipoprotein B100 was reduced 33% (p = 0.043). No adverse events occurred. Ezetimibe appears safe and effective in patients with HIV when added to maximally tolerated doses of lipid lowering therapy.
    背景与目标: :为了确定在HIV血脂异常患者中最大耐受性降脂治疗中添加依折麦布的疗效和安全性。回顾性分析了33名HIV病人,这些病人每天服用处方依泽替米贝10 mg。平均总胆固醇降低了21%(p <0.001)。平均LDL降低了35%(p <0.001)。平均HDL增加8%(p = 0.038)。平均甘油三酸酯减少了34%(p = 0.006)。平均载脂蛋白B100降低了33%(p = 0.043)。没有发生不良事件。当加入最大耐受剂量的降脂治疗时,依泽替米贝在HIV患者中似乎是安全有效的。
  • 【心肌梗死和心肌离子通道疾病诱发的致死性室性前庭性心律失常(LVTA)的常见脂质特征。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-04620-w 复制DOI
    作者列表:Wu J,Wu Q,Wang D,Kong J,Dai W,Wang X,Yu X
    BACKGROUND & AIMS: :Lethal ventricular tachyarrhythmia (LVTA) is the most prevalent electrophysiological underpinning of sudden cardiac death (SCD), a condition that occurs in response to multiple pathophysiological abnormalities. The aim of this study was to identify common lipid features of LVTA that were induced by distinct pathophysiological conditions, thereby facilitating the discovery of novel SCD therapeutic targets. Two rat LVTA-SCD models were established to mimic myocardial infarction (MI) and myocardial ion channel diseases. Myocardial and serum specimens were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based lipidomics. The lipid profiles of the myocardial and serum specimens were similar between the models. Eleven myocardial lipid classes were altered, including downregulations of: cardiolipin, ceramide, phosphatidylinositol, phosphatidylethanolamine, triacylglycerol, diacylglycerol, phosphatidylglycerol, lysophosphatidylethanolamine and phosphatidylserine, and upregulations of: lysophosphatidylcholine and phosphatidic acid. Serum concentrations of triacylglycerol, lysophosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol were also altered. Alterations of lipids in paired myocardia and sera were closely correlated. Cardiolipin 70:5, cardiolipin 74:9 and ceramide d34:2 were tested as potential biomarkers of LVTA. The results indicate that there are common LVTA lipid profiles induced by MI and myocardial ion channel diseases, potentially offering novel LVTA-SCD therapeutic targets.
    背景与目标: :致命性室性心律失常(LVTA)是心脏猝死(SCD)的最普遍的电生理基础,这种情况是由于多种病理生理异常而引起的。这项研究的目的是确定由不同的病理生理条件诱导的LVTA的常见脂质特征,从而促进新的SCD治疗靶标的发现。建立了两种大鼠LVTA-SCD模型来模拟心肌梗塞(MI)和心肌离子通道疾病。使用基于超高效液相色谱-质谱(UPLC-MS)的脂质组学分析心肌和血清标本。在两个模型之间,心肌和血清标本的脂质谱相似。改变了11种心肌脂质的类别,包括下调:心磷脂,神经酰胺,磷脂酰肌醇,磷脂酰乙醇胺,三酰基甘油,二酰基甘油,磷脂酰甘油,溶血磷脂酰乙醇胺和磷脂酰丝氨酸,以及溶血磷脂酰磷酸的上调。血清三酰甘油,溶血磷脂酰胆碱,磷脂酰乙醇胺和磷脂酰肌醇的浓度也发生了改变。配对的心肌和血清中脂质的变化密切相关。心磷脂70:5,心磷脂74:9和神经酰胺d34:2被测试为LVTA的潜在生物标志物。结果表明存在由MI和心肌离子通道疾病引起的常见LVTA脂质谱,可能提供新的LVTA-SCD治疗靶标。
  • 【通过概述海胆感知和信号级联来探测纳米粒子的安全性。】 复制标题 收藏 收藏
    DOI:10.1016/j.ecoenv.2017.06.060 复制DOI
    作者列表:Alijagic A,Pinsino A
    BACKGROUND & AIMS: :Among currently identified issues presenting risks and benefits to human and ocean health, engineered nanoparticles (ENP) represent a priority. Predictions of their economic and social impact appear extraordinary, but their release in the environment at an uncontrollable rate is in striking contrast with the extremely limited number of studies on environmental impact, especially on the marine environment. The sea urchin has a remarkable sensing environmental system whose function and diversity came into focus during the recent years, after sea urchin genome sequencing. The complex immune system may be the basis wherefore sea urchins can adapt to a dynamic environment and survive even in hazardous conditions both in the adult and in the embryonic life. This review is aimed at discussing the literature in nanotoxicological/ecotoxicological studies with a focus on stress and innate immune signaling in sea urchins. In addition, here we introduce our current development of in vitro-driven probes that could be used to dissect ENP aftermaths, suggesting their future use in immune-nanotoxicology.
    背景与目标: :在目前发现的对人类和海洋健康构成风险和益处的问题中,工程纳米颗粒(ENP)成为重中之重。对它们的经济和社会影响的预测似乎非同寻常,但它们以不可控制的速度释放到环境中,与对环境影响,特别是对海洋环境的研究数量极为有限形成鲜明对比。在海胆基因组测序之后,海胆具有卓越的传感环境系统,近年来其功能和多样性成为人们关注的焦点。复杂的免疫系统可能是海胆能够适应动态环境并在成年和胚胎生命中甚至在危险条件下生存的基础。这篇综述旨在讨论纳米毒理学/生态毒理学研究中的文献,重点是海胆中的压力和先天性免疫信号传导。此外,在这里,我们介绍了体外驱动探针的最新进展,该探针可用于剖析ENP后果,表明它们在免疫纳米毒理学中的未来用途。
  • 【细针抽吸与基质辅助激光解吸电离飞行时间/质谱联用,表征脂质生物标志物,以诊断乳腺癌的准确性。】 复制标题 收藏 收藏
    DOI:10.1016/j.clbc.2017.04.014 复制DOI
    作者列表:Cho YT,Su H,Chiang YY,Shiea J,Yuan SF,Hung WC,Yeh YT,Hou MF
    BACKGROUND & AIMS: BACKGROUND:Fine needle aspiration (FNA) cytology has been widely used for pathologic assessment of breast lesions. However, the examination suffers a risk of false-negative results owing to insufficient sample volumes, inaccurate sampling positions, nondefinitive cytologic features, or suboptimal cell preservation. One approach to improve its accuracy is using modern mass spectrometry to detect disease biomarkers, of which the tissue samples are collected through FNA. METHODS:The biological compounds in the FNA tissue samples were extracted and characterized by matrix-assisted laser desorption ionization time-of-flight/mass spectrometry (MALDI-TOF/MS). The results were further analyzed by principal component analysis. Distribution of lipid biomarkers on tissues was explored by imaging mass spectrometry. RESULTS:Lipid profiles of the tissue samples collected by FNA were rapidly obtained through MALDI-TOF/MS analysis. Phosphatidylcholines and triacylglycerols were detected as the predominant compounds in cancerous and normal regions, respectively. The samples were clearly classified by principal component analysis, based on the differences in their lipid profiles. Different lipid patterns were clearly viewed through the molecular imaging of normal and tumorous regions of breast tissue samples. CONCLUSION:The FNA-MALDI-TOF/MS approach can provide complementary information for pathological examinations and improve the accuracy of breast cancer diagnoses. Owing to the ease of operation and automation, it is possible to efficiently screen the lipid biomarkers in a large number of tissue samples by means of MALDI-TOF/MS.
    背景与目标: 背景:细针穿刺(FNA)细胞学检查已被广泛用于乳腺病变的病理评估。但是,由于样品量不足,采样位置不正确,细胞学特征不确定或细胞保存效果欠佳,检查可能会出现假阴性结果。一种提高其准确性的方法是使用现代质谱检测疾病生物标志物,其中的组织样本是通过FNA收集的。
    方法:通过基质辅助激光解吸电离飞行时间/质谱(MALDI-TOF / MS)提取FNA组织样品中的生物化合物并进行表征。通过主成分分析进一步分析结果。通过成像质谱研究脂质生物标志物在组织上的分布。
    结果:通过MALDI-TOF / MS分析快速获得了由FNA收集的组织样品的脂质概况。磷脂酰胆碱和三酰基甘油分别作为癌性和正常区域中的主要化合物被检测到。根据样品的脂质谱差异,通过主成分分析将样品明确分类。通过对乳腺组织样本的正常和肿瘤区域进行分子成像,可以清楚地观察到不同的脂质模式。
    结论:FNA-MALDI-TOF / MS方法可为病理检查提供补充信息,并提高乳腺癌诊断的准确性。由于操作和自动化的简便性,可以通过MALDI-TOF / MS有效地筛查大量组织样品中的脂质生物标志物。
  • 【各种应激调节因子对微藻藻球菌生物量和脂质产生的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.biortech.2012.10.049 复制DOI
    作者列表:Saha SK,McHugh E,Hayes J,Moane S,Walsh D,Murray P
    BACKGROUND & AIMS: :To maximize the biomass and lipid production for applications in food or biofuel feedstock, nine stress conditions were tested considering N and/or P limitations, light intensity & quality, for Haematococcus pluvialis SCCAP K-0084 cultivation. Photosynthetically active radiation (PAR), warm white light emitting diode (WWLED), and white light emitting diode (WLED) at illumination of 240 μmol photons m(-2) sec(-1) were the best stress-regulatory factors. PAR without P & low N conditions yielded high biomass with 33% lipids containing increased C16:0 and C18:0 saturated fatty acids, and reduced unsaturated fatty acids (UFAs) (oleic, linoleic, and α/γ-linolenic). WWLED and WLED without P conditions also yielded high biomass, but 25% lipids with increased amounts of UFAs. Red light emitting diode (RLED) without P & low N conditions yielded 46% lipids with lowest biomass. PAR and WWLED & WLED illuminated conditions were found suitable respectively for biodiesel feedstock lipids and UFA-rich lipids for multiple applications.
    背景与目标: :为了使生物质和脂质的生产最大化以用于食品或生物燃料原料,测试了九种胁迫条件,考虑了氮和/或磷的限制,光强度和质量,适用于雨生红球菌SCCAP K-0084的培养。在240μmol光子m(-2)sec(-1)的光照下,光合有效辐射(PAR),暖白光发光二极管(WWLED)和白光发光二极管(WLED)是最佳的应力调节因子。没有P和低N条件的PAR产生了高生物量,其中33%的脂质包含增加的C16:0和C18:0饱和脂肪酸,以及减少的不饱和脂肪酸(UFAs)(油酸,亚油酸和α/γ-亚麻酸)。没有P条件的WWLED和WLED也产生高生物量,但是25%的脂质具有增加的UFA含量。没有P和低N条件的红色发光二极管(RLED)产生了46%的脂质,具有最低的生物量。发现PAR和WWLED和WLED照明的条件分别适合于生物柴油原料脂质和富含UFA的脂质的多种应用。
  • 【乙酰化可以稳定ATP柠檬酸裂解酶,从而促进脂质的生物合成和肿瘤的生长。】 复制标题 收藏 收藏
    DOI:10.1016/j.molcel.2013.07.002 复制DOI
    作者列表:Lin R,Tao R,Gao X,Li T,Zhou X,Guan KL,Xiong Y,Lei QY
    BACKGROUND & AIMS: :Increased fatty acid synthesis is required to meet the demand for membrane expansion of rapidly growing cells. ATP-citrate lyase (ACLY) is upregulated or activated in several types of cancer, and inhibition of ACLY arrests proliferation of cancer cells. Here we show that ACLY is acetylated at lysine residues 540, 546, and 554 (3K). Acetylation at these three lysine residues is stimulated by P300/calcium-binding protein (CBP)-associated factor (PCAF) acetyltransferase under high glucose and increases ACLY stability by blocking its ubiquitylation and degradation. Conversely, the protein deacetylase sirtuin 2 (SIRT2) deacetylates and destabilizes ACLY. Substitution of 3K abolishes ACLY ubiquitylation and promotes de novo lipid synthesis, cell proliferation, and tumor growth. Importantly, 3K acetylation of ACLY is increased in human lung cancers. Our study reveals a crosstalk between acetylation and ubiquitylation by competing for the same lysine residues in the regulation of fatty acid synthesis and cell growth in response to glucose.
    背景与目标: :需要增加脂肪酸的合成才能满足快速生长的细胞膜扩张的需求。 ATP柠檬酸裂合酶(ACLY)在几种类型的癌症中被上调或激活,对ACLY的抑制会阻止癌细胞的增殖。在这里,我们显示ACLY在赖氨酸残基540、546和554(3K)处被乙酰化。在高葡萄糖下,这三个赖氨酸残基的乙酰化受到P300 /钙结合蛋白(CBP)相关因子(PCAF)乙酰转移酶的刺激,并通过阻止其泛素化和降解来提高ACLY的稳定性。相反,蛋白质脱乙酰基酶Sirtuin 2(SIRT2)会脱乙酰基并使ACLY不稳定。 3K取代消除了ACLY泛素化并促进了从头脂质合成,细胞增殖和肿瘤生长。重要的是,人类肺癌中ACLY的3K乙酰化增加。我们的研究揭示了乙酰化和泛素化之间的串扰,它们通过竞争相同的赖氨酸残基来调节脂肪酸合成和响应葡萄糖的细胞生长。
  • 【通过使用CdSO4纳米颗粒新型增强TiO2的光催化活性,可有效地浓缩浓溶液中的灭多米农药。】 复制标题 收藏 收藏
    DOI:10.1007/s11356-013-2027-9 复制DOI
    作者列表:Barakat NA,Nassar MM,Farrag TE,Mahmoud MS
    BACKGROUND & AIMS: :Annihilation of electrons-holes recombination process is the main remedy to enhance the photocatalytic activity of the semiconductors photocatalysts. Doping of this class of photocatalysts by foreign nanoparticles is usually utilized to create high Schottky barrier that facilitates electron capture. In the literature, because nonpolar nanoparticles (usually pristine metals, e.g., Ag, Pt, Au, etc.) were utilized in the doping process, the corresponding improvement was relatively low. In this study, CdSO4-doped TiO2 nanoparticles are introduced as a powerful and reusable photocatalyst for the photocatalytic degradation of methomyl pesticide in concentrated aqueous solutions. The utilized CdSO4 nanoparticles form polar grains in the TiO2 matrix due to the electrons leaving characteristic of the sulfate anion. The introduced nanoparticles could successfully eliminate the harmful pesticide under the sunlight radiation within a very short time (less than 1 h), with a removal capacity reaching 1,000 mg pesticide per gram of the introduced photocatalyst. Moreover, increase in the initial concentration of the methomyl did not affect the photocatalytic performance; typically 300, 500, 1,000, and 2,000 mg/l solutions were completely treated within 30, 30, 40, and 60 min, respectively, using 100 mg catalyst. Interestingly, the photocatalytic efficiency was not affected upon multiple use of the photocatalyst. Moreover, negative activation energy was obtained which reveals super activity of the introduced photocatalyst. The distinct photocatalytic activity indicates the complete annihilation of the electrons-holes recombination process and abundant existence of electrons on the catalyst surfaces due to strong electrons capturing the operation of the utilized polar CdSO4 nanoparticles. The introduced photocatalyst has been prepared using the sol-gel technique. Overall, the simplicity of the synthesizing procedure and the obtained featured photocatalytic activity strongly recommend the introduced nanoparticles to treat the methomyl-containing polluted water.
    背景与目标: 电子-空穴复合过程的Ann灭是增强半导体光催化剂光催化活性的主要手段。通常利用外来纳米颗粒对这类光催化剂进行掺杂,以产生促进电子捕获的高肖特基势垒。在文献中,由于在掺杂过程中利用了非极性纳米颗粒(通常是原始金属,例如Ag,Pt,Au等),因此相应的改进相对较低。在这项研究中,CdSO4掺杂的TiO2纳米颗粒被引入作为一种强大且可重复使用的光催化剂,用于在浓水溶液中光催化降解灭多明农药。由于电子留下了硫酸根阴离子的特性,因此所利用的CdSO4纳米颗粒在TiO2基体中形成了极性晶粒。引入的纳米粒子可以在非常短的时间内(不到1小时)成功地在阳光辐射下成功清除有害农药,其去除能力达到每克引入的光催化剂1000毫克农药。此外,甲基苯丙胺的初始浓度的增加不会影响光催化性能。通常使用100 mg催化剂分别在30、30、40和60分钟内分别处理300、500、1,000和2,000 mg / l溶液。有趣的是,光催化剂的效率不受光催化剂多次使用的影响。此外,获得了负的活化能,其揭示了所引入的光催化剂的超活性。独特的光催化活性表明电子-空穴复合过程完全消失,并且由于强电子捕获了所利用的极性CdSO4纳米颗粒的操作,电子在催化剂表面上大量存在。引入的光催化剂已经使用溶胶-凝胶技术制备。总体而言,合成过程的简便性和所获得的特征性光催化活性强烈推荐引入的纳米颗粒用于处理含甲met的污水。
  • 【对靶向乳腺癌细胞的新型可生物降解纳米粒子的比较评估。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejpb.2013.07.016 复制DOI
    作者列表:Mattu C,Pabari RM,Boffito M,Sartori S,Ciardelli G,Ramtoola Z
    BACKGROUND & AIMS: :Nanomedicine formulations such as biodegradable nanoparticles (nps) and liposomes offer several advantages over traditional routes of administration: due to their small size, nanocarriers are able to selectively accumulate inside tumours or inflammatory tissues, resulting in improved drug efficacy and reduced side effects. To further augment targeting ability of nanoparticles towards tumour cells, specific ligands or antibodies that selectively recognise biomarkers over-expressed on cancer cells, can be attached to the surface either by chemical bond or by hydrophilic/hydrophobic interactions. In the present work, Herceptin (HER), a monoclonal antibody (mAb) able to selectively recognise HER-2 over-expressing tumour cells (such as breast and ovarian cancer cells), was absorbed on the surface of nanoparticles through hydrophilic/hydrophobic interactions. Nps were prepared by a modified single emulsion solvent evaporation method with five different polymers: three commercial polyesters (poly(ε-caprolactone) (PCL), poly (D,L-lactide) (PLA) and poly (D,L-lactide-co-.glycolide) (PLGA)) and two novel biodegradable polyesterurethanes (PURs) based on Poly(ε-caprolactone) blocks, synthesised with different chain extenders (1,4-cyclohexane dimethanol (CDM) and N-Boc-serinol). Polyurethanes were introduced as matrix-forming materials for nanoparticles due to their high chemical versatility, which allows tailoring of the materials final properties by properly selecting the reagents. All nps exhibited a small size and negative surface charge, suitable for surface functionalisation with mAb through hydrophilic/hydrophobic interactions. The extent of cellular internalisation was tested on two different cell lines: MCF-7 and SK-BR-3 breast cancer cells showing a normal and a high expression of the HER-2 receptor, respectively. Paclitaxel, a model anti-neoplastic drug, was encapsulated inside all nps, and release profiles and cytotoxicity on SK-BR-3 cells were also assessed. Interestingly, PUR nps were superior to commercial polyester-based nps in terms of higher cellular internalisation and cytotoxic activity on the tested cell lines. Results obtained warrants further investigation on the application of these PUR nps for controlled drug delivery and targeting.
    背景与目标: 纳米生物制剂,例如可生物降解的纳米颗粒(nps)和脂质体,与传统的给药途径相比具有许多优势:由于纳米载体的体积小,它们能够选择性地积聚在肿瘤或炎性组织内部,从而提高了药效并降低了副作用。为了进一步增强纳米颗粒对肿瘤细胞的靶向能力,可以通过化学键或通过亲水/疏水相互作用将选择性识别在癌细胞上过度表达的生物标志物的特异性配体或抗体附着于表面。在本研究中,赫赛汀(HER)是一种能够选择性识别过度表达HER-2的肿瘤细胞(如乳腺癌和卵巢癌细胞)的单克隆抗体(mAb),通过亲水/疏水相互作用被吸收在纳米颗粒表面。通过改良的单乳液溶剂蒸发法用五种不同的聚合物制备Nps:五种不同的聚合物:三种市售聚酯(聚(ε-己内酯)(PCL),聚(D,L-丙交酯)(PLA)和聚(D,L-丙交酯-乙交酯(PLGA))和两种基于聚(ε-己内酯)嵌段的新型可生物降解聚酯聚氨酯(PUR),它们是用不同的扩链剂(1,4-环己烷二甲醇(CDM)和N-Boc-丝氨醇)合成的。聚氨酯被引入作为用于纳米颗粒的基质形成材料由于它们的高的化学的通用性,这允许通过适当地选择所用试剂剪裁材料最终特性。所有nps均显示出较小的尺寸和负表面电荷,适用于通过亲水/疏水相互作用与mAb进行表面官能化。在两种不同的细胞系上测试了细胞内在化的程度:MCF-7和SK-BR-3乳腺癌细胞分别显示出HER-2受体的正常表达和高表达。紫杉醇是一种抗肿瘤药物,被封装在所有nps内,并评估了其在SK-BR-3细胞上的释放特性和细胞毒性。有趣的是,在更高的细胞内在化和对测试细胞系的细胞毒活性方面,PUR nps优于市售的基于聚酯的nps。获得的结果值得进一步研究这些PUR nps在控制药物递送和靶向中的应用。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录