• 【含有细菌视紫红质的两相脂质双层中渗透的荧光猝灭和电子自旋共振研究。】 复制标题 收藏 收藏
    DOI:10.1016/S0006-3495(97)78909-4 复制DOI
    作者列表:Piknová B,Marsh D,Thompson TE
    BACKGROUND & AIMS: The effect of bacteriorhodopsin (BR) on the percolation properties of dimyristoylphosphatidylcholine/distearoylphosphatidylcholine bilayers was examined by studying the quenching of a lipid-bound fluorophore by a lipid-bound quencher, and by spin-spin interactions of a nitroxide-labeled lipid using electron spin resonance (ESR). At the low concentrations of BR used, differential scanning calorimetry showed that although the transition enthalpy was reduced in a concentration-dependent manner by incorporation of BR, the solidus and fluidus phase boundaries and overall shape of the heat capacity profiles were essentially unchanged. However, fluorescence quenching and spin-label ESR data showed that the domain topology, as reflected in the percolation properties, is strongly affected by the protein. In contrast to our previous fluorescence data for the pure lipid mixtures, quenching in the coexistence region is independent of the fluid phase fraction when BR is present. In addition, the percolation threshold estimated by spin-label ESR is shifted in the presence of BR to a higher gel phase fraction at a given lipid composition. Both the fluorescence quenching and spin-label ESR data, together with the results of earlier simulations, strongly suggest that the fluid phase domains are substantially larger and/or less ramified in the presence of BR than in its absence. We have previously reported a similar effect of a transmembrane peptide, pOmpA (Escherichia coli outer membrane protein A signal peptide), on fluid domain connectivity in binary phosphatidylcholine mixtures.

    背景与目标: 通过研究脂质结合的猝灭剂对脂质结合的荧光团的猝灭以及通过自旋-自旋相互作用,研究了细菌视紫红质 (BR) 对二肉豆蔻酰磷脂酰胆碱/二硬脂酰磷脂酰胆碱双层的渗透特性的影响。使用电子自旋共振 (ESR)。在使用低浓度的BR时,差示扫描量热法表明,尽管通过掺入BR以浓度依赖的方式降低了过渡焓,但固相线和流相界以及热容分布的整体形状基本上没有变化。然而,荧光猝灭和自旋标记ESR数据表明,渗透特性所反映的结构域拓扑受到蛋白质的强烈影响。与我们先前的纯脂质混合物的荧光数据相反,存在BR时,共存区域的猝灭与液相分数无关。此外,在给定的脂质组成下,在BR的存在下,由自旋标记ESR估计的渗滤阈值被转移到更高的凝胶相分数。荧光猝灭和自旋标记ESR数据以及较早的模拟结果都强烈表明,在存在BR的情况下,流体相域比不存在BR的情况下要大得多和/或分支更少。我们以前曾报道过跨膜肽pOmpA (大肠杆菌外膜蛋白a信号肽) 对二元磷脂酰胆碱混合物中流体结构域连通性的类似作用。
  • 【贝伐单抗和厄洛替尼靶向治疗适合复发性胶质母细胞瘤患者的分子特征.初步经验。】 复制标题 收藏 收藏
    DOI:10.1007/s00701-012-1536-5 复制DOI
    作者列表:D'Alessandris QG,Montano N,Cenci T,Martini M,Lauretti L,Bianchi F,Larocca LM,Maira G,Fernandez E,Pallini R
    BACKGROUND & AIMS: BACKGROUND:Advances in comprehension of molecular biology of glioblastoma (GBM) have led to the development of targeted therapies. The aim of the present study was to evaluate the efficacy and safety of a targeted therapeutic approach in which administration of bevacizumab and erlotinib was tailored on the molecular profile of recurrent GBM. METHODS:We prospectively enrolled ten adult patients suffering from recurrent GBM who had undergone surgical resection and standard chemo-radiotherapy. Tumor tissue was assessed for the expression of EGFRvIII and MGMT promoter methylation by RT-PCR, and for PTEN and VEGF expression by immunohistochemistry. Normal PTEN status was required for inclusion. Patients with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg iv every 2 weeks in 6-week cycles); patients whose tumor expressed EGFRvIII (4/10) added erlotinib (150 mg/day orally; 300 mg/day if on enzyme-inducing antiepileptic drugs). Therapy was continued until disease progression or unacceptable toxicity. Primary endpoints of the study were response rate (RR), 6-month progression-free survival (PFS-6), and safety profile. RESULTS:The RR and PFS-6 were 100 % (4/4) and 50 % (3/6) in patients treated with bevacizumab+erlotinib (n = 4) and bevacizumab (n = 6), respectively. In the whole cohort (n = 10), RR and PFS-6 were both 70 % (7/10); median PFS and overall survival (OS) were 8.0 (3.0-31.0) and 9.5 (5.0-31.0) months, respectively. No grade 3/4 adverse events were observed; three patients treated with bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one patient treated with bevacizumab developed intratumoral hemorrhage requiring treatment discontinuation. CONCLUSION:To our knowledge, this is the first study on recurrent GBM in which administration of bevacizumab and erlotinib was tailored on the molecular profile of the patient's tumor. Although we treated a limited number of patients, we obtained significantly higher RR and PFS-6 than those reported in a previous trial lacking molecular tumor analysis.
    背景与目标:
  • 【Gordonia sp.Ktr9中脂质积累和体内酯形成的生理特征。】 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: : 以前的工作已经证明了在大肠杆菌中体内合成生物柴油的可行性,但是,乙酯的形成取决于外部脂肪酸原料。与大肠杆菌相反,放线菌可能是直接合成生物柴油的理想生物,因为它们具有合成高水平的三酰基玻璃酸酯 (标签) 的能力。在这项研究中,我们研究了Gordonia sp. KTR9的生理和相关TAG积累以及体内催化外源短链醇源形成酯的能力,该菌株具有大量专用于脂肪酸和脂质生物合成的基因。在氮饥饿条件下,菌株ktr9的总脂质脂肪酸含量增加75%,TAG含量增加50%。菌株KTR9耐受培养基中最多4% 甲醇、4% 乙醇和2% 丙醇的外源添加。酒精浓度的增加导致回收的脂肪酸醇酯的饱和度降低,脂肪酸链长度略有增加。与在没有醇的情况下生长的对照KTR9菌株相比,在0.5 2% 的甲醇和乙醇存在下观察到脂肪醇酯合成中的线性剂量依赖性。对KTR9基因组的检查显示,存在几种推定的蜡酯合酶/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,可以催化体内合成脂肪酸短链醇的酯。总的来说,这些结果表明Gordonia sp。KTR9可能是用于体内生物柴油合成的合适的放线菌宿主菌株。
  • 【Trichosporon dermatis在玉米芯酸水解产物和大豆油的混合培养基中结合了 “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:
  • 【豆奶可抑制胆固醇诱导的炎症基因表达,并改善SD大鼠皮肤中的脂肪酸谱。】 复制标题 收藏 收藏
    DOI:10.1016/j.bbrc.2012.10.074 复制DOI
    作者列表:Lee SM,Kim Y,Choi Hj,Choi J,Yi Y,Yoon S
    BACKGROUND & AIMS: :Recently, an elevation in skin cholesterol level has been implicated in skin inflammation. Given the potential therapeutic effects of soy on low grade inflammatory diseases, we hypothesized that a CHOL diet could promote an inflammatory response in skin and that soy milk (SM) or fermented soy milk (F.SM) could prevent this cholesterol-induced skin inflammation. To test this hypothesis, freeze-dried SM or F.SM was provided as a protein replacement for 20% of the casein in the diets of Sprague-Dawley (SD) rats. The animals were divided into the following groups: (1) control group (CTRL), AIN76A diet without cholesterol, (2) high cholesterol (CHOL) group, AIN76A with 1% (w/w) cholesterol, (3) SM group, CHOL diet with freeze-dried SM, and (4) F.SM group, CHOL diet with F.SM. In the CHOL group, the expression levels of pro-inflammatory genes, including IL-1β, IL-1α, iNOS, and COX-2, were elevated. In comparison, the SM and F.SM groups displayed the lowered expression of IL-1β, COX-2, F4/80, and Cd68, an increase of a n-3/n-6 ratio, and a reduction in the estimated desaturase activities of delta 5 desaturase (D5D) and steaoryl CoA desaturase (SCD-1). In particular, F.SM significantly increased the proportion of dihomo-γ-linolenic acid (DGLA) in skin fatty acid (FA) composition compared with the CHOL group. Here we present evidence that SM or F.SM could alleviate the inflammatory response in the skin that is triggered by excess dietary cholesterol by reducing the expression of pro-inflammatory genes. This response could be partly associated with a decreased in macrophages in skin and/or by modulation of the skin's FA composition.
    背景与目标: : 最近,皮肤胆固醇水平的升高与皮肤炎症有关。鉴于大豆对低度炎症性疾病的潜在治疗作用,我们假设CHOL饮食可以促进皮肤的炎症反应,并且豆浆 (SM) 或发酵豆浆 (F.SM) 可以预防这种胆固醇引起的皮肤炎症。为了检验这一假设,提供了冻干SM或F.SM作为蛋白质替代物,用于在Sprague-Dawley (SD) 大鼠的饮食中20% 酪蛋白。将动物分为以下组 :( 1) 对照组 (CTRL),AIN76A饮食无胆固醇,(2) 高胆固醇 (CHOL) 组,AIN76A 1% (w/w) 胆固醇,(3) SM组,CHOL饮食加冻干SM,和 (4) F.SM组,CHOL饮食与F.SM。在CHOL组中,促炎基因 (包括IL-1β,IL-1α,iNOS和COX-2) 的表达水平升高。相比之下,SM和F.SM组显示出IL-1β,COX-2,F4/80和Cd68的表达降低,n-3/n-6比增加以及delta 5的估计去饱和酶活性降低。去饱和酶 (D5D) 和steaoryl CoA去饱和酶 (SCD-1)。特别是,与CHOL组相比,F.SM显着增加了皮肤脂肪酸 (FA) 组成中二高-γ-亚麻酸 (DGLA) 的比例。在这里,我们提供了证据,表明SM或F。SM可以通过减少促炎基因的表达来减轻由过量饮食胆固醇引发的皮肤炎症反应。这种反应可能部分与皮肤中巨噬细胞的减少和/或通过调节皮肤的FA组成有关。
  • 【叶绿体超微结构和膜脂组成与菠菜,常春藤和云杉叶片中不同程度的抗冻性的相关性。】 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: : 中度耐寒 (菠菜) 的叶子,非常耐寒 (常春藤) 和极端耐寒 (云杉) 植物 [根据Levitt {1980分类] 在膜脂质组成和叶绿体超微结构的变化方面表现出特征差异,这与每种类型的组织在适应亚-零温度。菠菜叶在霜冻硬化后总脂质含量没有增加。相反,半乳糖脂的数量大大减少,而磷脂的数量仅略有增加。没有观察到从饱和棕榈酸到三倍不饱和亚麻酸的转变。在霜冻硬化期间,常春藤叶和云杉针的膜脂质含量增加到类似的程度。然而,与云杉针相反,在常春藤叶片中观察到磷脂的明显优先积累,导致PL/GL比增加。在两种植物中检测到从饱和 (棕榈酸) 到不饱和脂肪酸的相当大的转变,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,但常春藤叶片中每个细胞的叶绿体数量没有增加,尽管类囊体的长度几乎增加了一倍,并且质体似乎处于分裂阶段: 但是,无法观察到真正的分裂。相反,在云杉针中观察到叶绿体和线粒体的数量增加。当常春藤或云杉的霜冻叶片暴露于零度以下的温度下,它们可以生存时,叶绿体包膜的许多大内陷就进一步明显增加了膜。
  • 【包括HDL在内的氧化脂蛋白及其脂质过氧化产物抑制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) 修饰巨噬细胞的细胞因子分泌,例如,通过减少肿瘤坏死因子 α (TNF-(α) m-RNA。然而,对氧化型高密度脂蛋白 (ox-HDL) 的影响知之甚少。这项研究报告了ox-HDL亚组分2和3 (ox-HDL2,ox-HDL3) 与ox-LDL和某些氧化产物 (氢过氧化物和醛) 对体外THP-1人单核细胞来源的巨噬细胞分泌TNF-α 的影响相比。HDL2,HDL3和LDL用10 microM Cu ++ 氧化12小时和/或24小时。将天然和氧化的HDL和LDL与有或没有LPS (10 ng/ml) 的巨噬细胞孵育24小时,然后在培养基中测量TNF-α 分泌。脂质氢过氧化物和极性醛还与细胞一起孵育2小时,然后更换培养基,再孵育22小时后测量TNF-α 分泌。ox-HDL2对TNF-α 的抑制作用 (p <.05),在存在和不存在LPS的情况下观察到来自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分泌TNF-α,而五在分析的八种醛中 (2,4-庚二烯醛,己醛,2-壬烯醛,2-辛烯醛,2,4-癸烯醛) 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,如先前对ox-LDL所观察到的,在巨噬细胞调节炎症反应中起作用。
  • 【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: 本研究旨在阐明使用脂质模型膜 (脂质体和平面脂质膜) 对有机化合物的毒性机理。研究的化合物是三烷基锡和三烷基氯化铅,二烷基锡二氯化物以及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) 洗涤剂来改变脂质体的表面性质。作为研究化合物与模型膜之间相互作用的量度,脂质体结合镨的释放以及在这些化合物的影响下平面膜的稳定性变化。根据获得的结果,推测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方面的不同因素的组合。决定有机化合物在相互作用中的行为的最重要特性是有机物不同部分的亲脂性和极性以及它们在介质中可以采用的空间排列。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可用性中起着重要作用,是相互作用的重要因素。
  • 【当将Ezetimibe添加到HIV患者的最大耐受降脂疗法中时,效果良好。】 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: : 确定在HIV血脂异常患者中添加依折米布最大耐受降脂治疗的有效性和安全性。对33例每天服用依泽替米布10 mg的HIV患者进行了脂质参数的回顾性分析。平均总胆固醇21% 降低 (p <0.001)。平均LDL 35% 降低 (p <0.001)。平均HDL 8% 增加 (p = 0.038)。平均甘油三酯34% 降低 (p = 0.006)。平均载脂蛋白B100 33% 降低 (p = 0.043)。无不良事件发生。当添加到最大耐受剂量的降脂疗法中时,依折米布对HIV患者似乎是安全有效的。
  • 【从动脉粥样硬化患者血液隔离动脉粥样硬化修饰的 (去唾液酸化的) 低密度脂蛋白: 通过亲和色谱与天然脂蛋白分离。】 复制标题 收藏 收藏
    DOI:10.1016/0006-291x(90)90639-5 复制DOI
    作者列表:Tertov VV,Sobenin IA,Tonevitsky AG,Orekhov AN,Smirnov VN
    BACKGROUND & AIMS: :A part of low density lipoproteins (LDL) isolated from the blood of healthy subjects and patients with coronary atherosclerosis bind to a Sepharose-linked Ricinus communis agglutinin, a lectin that interacts specifically with galactose residues. Bound LDL can be replaced by galactose, but not other saccharide constituents of the LDL molecule (mannose, glucose, N-acetylglucosamine, sialic acid). Bound LDL subfraction has a 2-3-fold lower content of sialic acid as compared with unbound LDL. The blood content of desialylated LDL in atherosclerotic patients was about 3-fold higher (1.5- to 6-fold) than in healthy subjects. Desialylated LDL induced a 2- to 4-fold more intensive accumulation of total cholesterol in cultured human aortic intimal cells. Unbound LDL had no effect on intracellular deposition of lipids. It is suggested that the subfraction of desialylated LDL may be responsible for the atherogenicity of LDL isolated from blood of atherosclerotic patients.
    背景与目标: : 从健康受试者和冠状动脉粥样硬化患者的血液中分离出的一部分低密度脂蛋白 (LDL) 与琼脂糖连接的蓖麻凝集素结合,凝集素与半乳糖残基特异性相互作用。结合的LDL可以用半乳糖代替,但不能用LDL分子的其他糖类成分 (甘露糖,葡萄糖,N-乙酰葡萄糖胺,唾液酸) 代替。与未结合的LDL相比,结合的LDL亚组分的唾液酸含量低2-3倍。动脉粥样硬化患者的去唾液酸化LDL的血液含量比健康受试者高约3倍 (1.5至6倍)。去唾液酸化的LDL在培养的人主动脉内膜细胞中诱导了2至4倍的总胆固醇密集积累。未结合的LDL对脂质的细胞内沉积没有影响。建议去唾液酸化的LDL的亚组分可能是从动脉粥样硬化患者血液中分离出的LDL的致动脉粥样硬化性的原因。
  • 【口服补充谷氨酸和GABA对大鼠海马记忆性能和神经化学特征的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Tabassum S,Ahmad S,Madiha S,Khaliq S,Shahzad S,Batool Z,Haider S
    BACKGROUND & AIMS: :Glutamate (GLU) and gamma-amino butyric acid (GABA) are essential amino acids (AA) for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water (control group) or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests (Novel object recognition test, Morris water maze, Passive avoidance test) measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine (ACh) were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance.
    背景与目标: 谷氨酸 (GLU) 和 γ-氨基丁酸 (GABA) 是脑功能必需氨基酸 (AA),分别作为兴奋性和抑制性神经递质。他们的片剂可用于改善肠道功能和肌肉性能。尽管在记忆形成和处理过程中起着重要作用,但尚未研究这些片剂对大脑功能 (如学习和记忆) 的影响。因此,本研究旨在研究口服补充的GLU和GABA对学习和记忆性能的影响,并进一步监测这些口服补充的GLU和GABA对这些AA的大脑水平的相关影响。三组大鼠分别口服补充饮用水 (对照组) 或GABA和谷氨酸混悬剂,持续4周。使用行为测试 (新颖物体识别测试,莫里斯水迷宫,被动回避测试) 来确定认知能力,以测量识别,空间参考和厌恶记忆。估计大鼠海马中GLU,GABA和乙酰胆碱 (ACh) 的水平。结果表明,长期口服GLU和GABA片对大鼠脑功能有明显影响,可改变大鼠海马GLU和GABA的含量。与GABA相比,补充GLU通过增加ACh来特别增强记忆性能。因此,GLU可以被建议作为改善学习和记忆性能以及大脑神经化学状态的有用补充,并且将来可以有效地治疗影响学习和记忆性能的神经系统疾病。
  • 【心室下区衍生的出生后神经母细胞转录谱的动态变化。】 复制标题 收藏 收藏
    DOI:10.1016/j.mod.2012.11.003 复制DOI
    作者列表:Khodosevich K,Alfonso J,Monyer H
    BACKGROUND & AIMS: :The subventricular zone (SVZ) of the lateral ventricles is a major neurogenic region in the postnatal mammalian brain. Thousands of neuroblasts are generated daily throughout the life of an animal. Newly born neuroblasts migrate via the rostral migratory stream (RMS) into the olfactory bulb where they mature into distinct neuronal subtypes. Neuroblasts exiting the SVZ retain the ability to proliferate, however, proliferation declines in the course of migration to the olfactory bulb. While migrating in the RMS, neuroblasts receive a plethora of stimuli that modify transcription according to the local microenvironment, and eventually modulate neuroblast migration. In the target area, the olfactory bulb, neuroblasts develop into mature neurons. In this review, we discuss dynamic changes of the transcriptome that occur during the "lifetime" of a neuroblast, thereby governing the activation or inhibition of distinct genes/pathways that are responsible for proliferation, migration and differentiation.
    背景与目标: 侧脑室下区 (SVZ) 是产后哺乳动物大脑中的主要神经源性区域。在动物的一生中,每天都会产生成千上万的神经母细胞。新生的神经母细胞通过鼻状迁移流 (RMS) 迁移到嗅球中,在那里它们成熟为不同的神经元亚型。离开SVZ的神经母细胞保留了增殖的能力,但是,在迁移到嗅球的过程中,增殖下降。在RMS中迁移时,神经母细胞会接受大量刺激,这些刺激会根据局部微环境改变转录,并最终调节神经母细胞的迁移。在靶区,嗅球、神经母细胞发育成成熟的神经元。在这篇综述中,我们讨论了在神经母细胞的 “寿命” 期间发生的转录组的动态变化,从而控制了负责增殖,迁移和分化的不同基因/途径的激活或抑制。
  • 【血管紧张素II诱导的心肌细胞自噬中长非编码RNA的差异表达谱。】 复制标题 收藏 收藏
    DOI:10.1002/cbin.10809 复制DOI
    作者列表:Gu Y,Yang F,Xu RM,Zhang YY,Li Y,Liu SX,Zhang GX,Wang GK,Ma LP
    BACKGROUND & AIMS: :Autophagy is a ubiquitous intracellular process for cellular homeostasis maintenance by recycling damaged protein and organelles. Dysregulation of cardiomyocytes autophagic activity is implicated in various heart diseases. Recent studies had demonstrated that long non-coding RNAs (lncRNAs) played crucial roles on modulation of autophagic activity. In this study, we first established an angiotensin II-induced autophagy model on neonatal rat cardiomyocytes. Western blot assay confirmed that the expression of Beclin 1 and the conversion of soluble LC3-I to lipid bound LC3-II were significantly increased at 12 h after angiotensin II stimulation, but the cardiomyocytes surface area and hypertrophic markers expression had no significant change. Then microarray analysis and real-time PCR were applied to detect differentially expressed lncRNAs during cardiomyocytes autophagy. A total of 1,249 lncRNAs were determined as differentially expressed, including 700 upregulated lncRNAs and 549 downregulated lncRNAs. LncRNAs subgroup analysis showed there were 43 transcribed ultra-conserved noncoding RNAs (T-UCRs) differentially expressed in cardiomyocytes autophagy, of which 26 T-UCRs were upregulated and 17 T-UCRs were downregulated. Bioinformatics analysis further showed that 94 differentially expressed lncRNAs contained potential binding sites of miR-22, a pro-hypertrophic and pro-autophagic microRNA. Therefore, these differentially expressed lncRNAs might play critical roles in cardiomyocytes autophagy. This finding would provide an experimental basis for future investigation on ischemic heart disease.
    背景与目标: : 自噬是一种普遍存在的细胞内过程,通过回收受损的蛋白质和细胞器来维持细胞稳态。心肌细胞自噬活性的失调与各种心脏病有关。最近的研究表明,长链非编码rna (lncRNAs) 在调节自噬活性中起关键作用。在这项研究中,我们首先在新生大鼠心肌细胞上建立了血管紧张素II诱导的自噬模型。Western blot检测证实,血管紧张素II刺激后12 h,Beclin 1的表达和可溶性LC3-I向脂质结合LC3-II的转化均显著增加,但心肌细胞表面积和肥厚标志物的表达无明显变化。然后应用微阵列分析和实时PCR检测心肌细胞自噬过程中差异表达的lncRNAs。总共1,249个lncrna被确定为差异表达,包括700上调的lncrna和549下调的lncrna。LncRNAs亚组分析显示,心肌细胞自噬中有43个转录的超保守非编码rna (t-ucr) 差异表达,其中26个t-ucr上调,17个t-ucr下调。生物信息学分析进一步表明,94个差异表达的lncrna包含miR-22的潜在结合位点,这是一种促肥厚和促自噬的microRNA。因此,这些差异表达的lncrna可能在心肌细胞自噬中起关键作用。这一发现将为未来缺血性心脏病的研究提供实验基础。
  • 【心肌梗塞和心肌离子通道疾病引起的致死性室性心律失常 (LVTAs) 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: : 致死性室性快速性心律失常 (LVTA) 是心脏性猝死 (SCD) 的最普遍的电生理基础,该疾病是针对多种病理生理异常而发生的。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,以模拟心肌梗塞 (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。模型之间心肌和血清标本的脂质分布相似。改变了11种心肌脂质类别,包括心磷脂,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的下调,以及溶血磷脂酰胆碱和磷脂酸的上调。三酰甘油,溶血磷脂酰胆碱,磷脂酰乙醇胺和磷脂酰肌醇的血清浓度也发生了变化。成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,MI和心肌离子通道疾病引起的常见LVTA脂质分布,可能为lvta-scd提供新的治疗靶标。
  • 【细针抽吸结合基质辅助激光解吸电离飞行时间/质谱法表征脂质生物标志物对乳腺癌诊断的准确性。】 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:

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