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。

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。

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。

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：

BACKGROUND & AIMS: :Facile fabrication of nanostructured surface is of great importance for the use of titanium (Ti) implants in biomedical field. In this study, a low-cost and easy-to-operate method called HPT (hydrothermal & pressure) here has been developed and used to fabricate the expected nanostructured surface on Ti substrates. The effects of experimental parameters on the morphology of Ti surface were investigated and characterized. The results indicated that by altering the hydrothermal pressure, NaOH concentration and treating time, surface nanostructure like nanopetals or nanoflakes could be formed on the surface of Ti substrates. The orthogonal experiments were conducted to demonstrate the optimized operation conditions. A formation mechanism of the nanostructured titanate layer was proposed, revealing that the nanostructured layer could be formed via a special upward and downward co-growth manner. In vitro cell culture showed that the HPT treated Ti substrates, especially the T-10 sample, could greatly enhance the cell-material interactions, i.e. the cell proliferation and differentiation, focal protein adhesion, and osteogenic factor expression. The HPT method paves a new way to modify the surface of Ti implants with better bioactivity and promising prospect for future biomedical applications.

背景与目标： : 纳米结构表面的简便制造对于在生物医学领域中使用钛 (Ti) 植入物非常重要。在这项研究中，已经开发了一种称为HPT (水热 & 压力) 的低成本且易于操作的方法，并将其用于在Ti衬底上制造预期的纳米结构表面。研究并表征了实验参数对Ti表面形貌的影响。结果表明，通过改变水热压力，NaOH浓度和处理时间，可以在Ti基材表面形成类似纳米颗粒或纳米薄片的表面纳米结构。进行正交实验以证明优化的操作条件。提出了纳米结构钛酸盐层的形成机理，揭示了纳米结构层可以通过特殊的向上和向下共生长方式形成。体外细胞培养表明，经HPT处理的Ti底物，尤其是T-10样品，可以大大增强细胞与物质的相互作用，即细胞增殖和分化，聚焦蛋白粘附和成骨因子的表达。HPT方法为修饰Ti植入物表面提供了一种新方法，具有更好的生物活性，并有望在未来的生物医学应用中获得广阔的前景。

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： : 为了最大限度地提高用于食品或生物燃料原料的生物量和脂质产量，对雨生红球藻SCCAP K-0084培养的九个胁迫条件进行了测试，考虑了氮和/或磷的限制、光强度和质量。在240 μ mol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) 是最佳的胁迫调节因子。没有P & 低N条件的PAR产生高生物量，其中33% 脂质含有增加的C16:0和C18:0饱和脂肪酸，以及减少的不饱和脂肪酸 (ufa) (油酸、亚油酸和 α/γ-亚麻酸)。没有磷条件的WWLED和WLED也产生高生物量，但25% 脂质，增加了UFAs的量。没有P & 低N条件的红色发光二极管 (RLED) 产生具有最低生物量的46% 脂质。发现PAR和WWLED和WLED照明条件分别适用于多种应用的生物柴油原料脂质和富含UFA的脂质。

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： : 需要增加脂肪酸合成，以满足快速生长的细胞对膜膨胀的需求。ATP-柠檬酸裂解酶 (ACLY) 在几种类型的癌症中被上调或激活，并且抑制ACLY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，P300/钙结合蛋白 (CBP) 相关因子 (PCAF) 乙酰转移酶刺激了这三个赖氨酸残基的乙酰化，并通过阻止其泛素化和降解来提高ACLY稳定性。相反，蛋白质脱乙酰酶sirtuin 2 (SIRT2) 脱乙酰并使ACLY不稳定。3k的取代可消除泛素化并促进从头脂质合成，细胞增殖和肿瘤生长。重要的是，在人类肺癌中，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，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。

BACKGROUND & AIMS: :Endocannabinoids regulate energy balance by modulating hypothalamic circuits controlling food intake and energy expenditure. However, convincing evidence has accumulated indicating that the endocannabinoid system is present also in peripheral tissues, in particular in adipose tissue. Fat cells produce (and are targets of) endocannabinoids. Adipogenesis, lipogenesis and glucose uptake are stimulated by endocannabinoids through CB(1) receptors and these effects are blocked by the CB(1) receptor antagonist rimonabant, suggesting that the weight-lowering effect of CB(1) receptor blockade is partly due to peripheral mechanisms. This review will focus on the role of endocannabinoids in adipose tissue metabolism, adipokine production and interactions between endocannabinoids and peroxisome proliferator activated receptors during adipogenesis.

背景与目标： : 内源性大麻素通过调节下丘脑回路控制食物摄入和能量消耗来调节能量平衡。然而，已经积累了令人信服的证据，表明内源性大麻素系统也存在于周围组织中，尤其是脂肪组织中。脂肪细胞产生 (并且是) 内源性大麻素的靶标。内源性大麻素通过CB(1) 受体刺激脂肪生成，脂肪生成和葡萄糖摄取，这些作用被CB(1) 受体拮抗剂利莫那班阻断，表明CB(1) 受体阻断的减肥作用部分是由于外围机制。本文将重点介绍内源性大麻素在脂肪组织代谢，脂肪因子产生以及内源性大麻素与过氧化物酶体增殖物激活受体之间的相互作用中的作用。

BACKGROUND & AIMS: :Biomembranes are thin capacitors with the unique feature of displaying phase transitions in a physiologically relevant regime. We investigate the voltage and lateral pressure dependence of their capacitance close to their chain melting transition. Because the gel and the fluid membrane have different area and thickness, the capacitance of the two membrane phases is different. In the presence of external fields, charges exert forces that can influence the state of the membrane, thereby influencing the transition temperature. This phenomenon is called "electrostriction". We show that this effect allows us to introduce a capacitive susceptibility that assumes a maximum in the melting transition with an associated excess charge. As a consequence, voltage regimes exist in which a small change in voltage can lead to a large uptake of charge and a large capacitive current. Furthermore, we consider electromechanical behavior such as pressure-induced changes in capacitance, and the application of such concepts in biology.

背景与目标： : 生物膜是薄电容器，具有在生理相关状态下显示相变的独特特征。我们研究了它们的电容接近其链熔化转变的电压和横向压力依赖性。由于凝胶和液膜具有不同的面积和厚度，因此两种膜相的电容不同。在存在外部场的情况下，电荷施加可以影响膜状态的力，从而影响转变温度。这种现象被称为 “电致伸缩”。我们证明，这种效应使我们能够引入电容性磁化率，该磁化率假定在熔化转变中具有最大的电荷，并带有相关的过量电荷。因此，存在电压状态，其中电压的小变化会导致电荷的大吸收和大电容电流。此外，我们考虑了机电行为，例如压力引起的电容变化，以及此类概念在生物学中的应用。

BACKGROUND & AIMS: :Lipid is an important energy source and essential component for plasma and organelle membranes in all kinds of cells. Coherent anti-Stokes Raman scattering (CARS) microscopy is a label-free and nonlinear optical technique that can be used to monitor the lipid distribution in live organisms. Here, we utilize CARS microscopy to investigate the pattern of lipid droplets in two live Caenorhabditis elegans mutants (fat-2 and fat-3). The CARS images showed a striking decrease in the size, number, and content of lipid droplets in the fat-2 mutant but a slight difference in the fat-3 mutant as compared with the wild-type worm. Moreover, a nondroplet-like structure with enhanced CARS signal was detected for the first time in the uterus of fat-2 and fat-3 mutants. In addition, transgenic fat-2 mutant expressing a GFP fusion protein of vitellogenin-2 (a yolk lipoprotein) revealed that the enhanced CARS signal colocalized with the GFP signal, which suggests that the nondroplet-like structure is primarily due to the accumulation of yolk lipoproteins. Together, this study implies that CARS microscopy is a potential tool to study the distribution of yolk lipoproteins, in addition to lipid droplets, in live animals.

背景与目标： : 脂质是各种细胞中血浆和细胞器膜的重要能量来源和必需成分。相干反斯托克斯拉曼散射 (CARS) 显微镜是一种无标记的非线性光学技术，可用于监测活生物体中的脂质分布。在这里，我们利用CARS显微镜研究了两个活秀丽隐杆线虫突变体 (fat-2和fat-3) 中脂质滴的模式。CARS图像显示，与野生型蠕虫相比，fat-2突变体中脂质滴的大小，数量和含量显着减少，但fat-3突变体略有差异。此外，首次在fat-2和fat-3突变体的子宫中检测到具有增强CARS信号的非液滴状结构。此外，表达vitellogenin-2 GFP融合蛋白 (卵黄脂蛋白) 的转基因fat-2突变体揭示了增强的CARS信号与GFP信号共定位，这表明非液滴状结构主要是由于卵黄脂蛋白的积累。总之，这项研究表明，CARS显微镜是研究活动物中除脂滴外卵黄脂蛋白分布的潜在工具。

BACKGROUND & AIMS: BACKGROUND:This study investigated the effects of comicronised fenofibrate in patients with dyslipidemia and polymetabolic syndrome X. DESIGN:After a 6-week dietary run-in phase, 37 male patients eligible on lipid criteria entered a 12-week treatment phase consisting of diet plus one capsule daily containing 200 mg of comicronised fenofibrate (Lipanthyl(R)). RESULTS:A significant reduction in plasma concentrations of total cholesterol, LDL cholesterol and triglyceride was observed after 4, 8 and 12 weeks of treatment with fenofibrate. The improvement in the atherogenic index LDL/HDL cholesterol from a pretreatment 3.8 to 3.0 after treatment was highly statistically significant and may be judged as satisfactory. Significant changes were also observed in haemostatic factors (fibrinogen reduced by 19%, factor VII activity reduced by 18%). Fasting serum insulin levels and insulin response (area under the curve) after oral glucose load were significantly reduced by 26.8% and 18.7%, respectively, indicating an improvement of insulin sensitivity. Systolic and diastolic blood pressure were significantly reduced. Uric acid was significantly reduced by 21.6%. CONCLUSION:These favourable effects of comicronised fenofibrate both on lipid and non lipid parameters, including insulin sensitivity, may confer to this product a particular interest in the treatment of patients with polymetabolic syndrome X.

背景与目标：

BACKGROUND & AIMS: A technique of measuring of the light-induced transients of the gramicidin-mediated electric current across a membrane in the presence of a photosensitizer has been applied for the study of the effect of agents modifying the dipole potential of a bilayer lipid membrane (phloretin, 6-ketocholestanol, and RH421) on the processes of the gramicidin channel dissociation and formation. It is shown that phloretin, known to lower the dipole potential, decelerates the flash-induced decrease in the current, whereas 6-ketocholestanol and RH421, known to raise the dipole potential, accelerate the current decrease. It is revealed that the addition of phloretin leads to a decrease in the dissociation rate constant, whereas addition of either 6-ketocholestanol or RH421 causes an increase in this constant. Single-channel data show that phloretin brings about an increase in the lifetime of the gramicidin channels, whereas RH421 produces a more complicated effect. It is conclude that the dipole potential affects the process of channel dissociation, presumably via the influence on the movement of the dipoles of gramicidin molecules through the layer of the dipole potential drop near the membrane-water interface.

背景与目标： 一种在光敏剂存在下测量短杆菌素介导的跨膜电流的光诱导瞬变的技术已用于研究试剂改变双层脂质膜偶极电位的作用 (根皮素，6-酮胆甾醇，和RH421) 对短杆菌素通道解离和形成的过程。表明，已知会降低偶极电位的根皮素会减慢闪光引起的电流降低，而已知会升高偶极电位的6-酮胆甾烷醇和RH421会加速电流降低。揭示了根皮素的添加会导致解离速率常数的降低，而6-酮胆甾烷醇或RH421的添加会导致该常数的增加。单通道数据表明，根皮素会增加短杆菌素通道的寿命，而RH421会产生更复杂的效果。结论是，偶极子电势影响通道解离的过程，大概是通过影响短杆菌肽分子的偶极子通过膜-水界面附近的偶极子电势下降层的运动。

BACKGROUND & AIMS: :CD45 is the most prominent membrane protein on lymphocytes. The function and regulation of this protein tyrosine phosphatase remain largely obscure, mainly because of the lack of a known ligand, and it still remains unknown whether such tyrosine phosphatases are subject to extracellular control at all. We report that an anti-CD45RB antibody (Ab) that prevents rejection and induces tolerance activates CD45RB tyrosine phosphatase enzymatic activity in T lymphocytes, allowing us to directly monitor the effects of increased CD45RB activity on signal transduction. Using both kinase substrate peptide arrays as well as conventional biochemistry, we also provide evidence of the various kinases involved in bringing about the inhibitory effect of this Ab on CD3-induced T-cell receptor signaling. Furthermore, we report that activated CD45RB translocates to lipid rafts and interferes with lipid raft localization and activation state of CD45 substrate Lck. Thus, these findings indeed prove that CD45 is subject to extracellular control and also define a novel mechanism by which receptor tyrosine phosphatases control lymphocyte biology and provide further insight into the intracellular signaling pathways effected by anti-CD45RB monoclonal Ab treatment.

背景与目标： : CD45是淋巴细胞上最突出的膜蛋白。这种蛋白质酪氨酸磷酸酶的功能和调节在很大程度上仍然不清楚，这主要是由于缺乏已知的配体，并且仍然未知这种酪氨酸磷酸酶是否完全受细胞外控制。我们报告了一种防止排斥和诱导耐受性的anti-CD45RB抗体 (Ab) 激活T淋巴细胞中的CD45RB酪氨酸磷酸酶酶活性，使我们能够直接监测CD45RB活性增加对信号转导的影响。使用激酶底物肽阵列以及常规生物化学，我们还提供了涉及这种Ab对CD3-induced T细胞受体信号传导的抑制作用的各种激酶的证据。此外，我们报道活化的CD45RB易位于脂筏，并干扰CD45底物Lck的脂筏定位和激活状态。因此，这些发现确实证明了CD45受细胞外控制，并且还定义了一种新的机制，通过该机制受体酪氨酸磷酸酶控制淋巴细胞生物学，并提供了对anti-CD45RB单克隆Ab治疗所影响的细胞内信号通路的进一步了解。

BACKGROUND & AIMS: :The dynamics of fluorescence quenching and the organization of a series of pyrene derivatives anchored in various depths in bilayers of phosphatidylcholine small unilamellar vesicles was studied and compared with their behavior in homogeneous solvent systems. The studies include characterization of the environmental polarity of the pyrene fluorophore based on its vibronic peaks, as well as the interaction with three collisional quenchers: the two membrane-soluble quenchers, diethylaniline and bromobenzene, and the water soluble quencher potassium iodide. The system of diethylaniline-pyrene derivatives in the membrane of phosphatidylcholine vesicles was characterized in detail. The diethylaniline partition coefficient between the lipid bilayers and the buffer is approximately 5,800. Up to a diethylaniline/phospholipid mole ratio of 1:3 the perturbation to membrane structure is minimal so that all photophysical studies were performed below this mole ratio. The quenching reaction, in all cases, was shown to take place in the lipid bilayer interior and the relative quenching efficiencies of the various probe molecules was used to provide information on the distribution of both fluorescent probes and quencher molecules in the lipid bilayer. The quenching efficiency by diethylaniline in the lipid bilayer was found to be essentially independent on the length of the methylene chain of the pyrene moiety. These findings suggest that the quenching process, being a diffusion controlled reaction, is determined by the mobility of the diethylaniline quencher (with an effective diffusion coefficient D approximately 10(-7) cm2 s-1) which appears to be homogeneously distributed throughout the lipid bilayer. The pulsed laser photolysis products of the charge-transfer quenching reaction were examined. No exciplex (excited-complex) formation was observed and the yield of the separated radical ions was shown to be tenfold smaller than in homogenous polar solutions. The decay of the radical ions is considerably faster than the corresponding process in homogenous solutions. Relatively high intersystem crossing yields are observed. The results are explained on the basis of the intrinsic properties of a lipid bilayer, primarily, its rigid spatial organization. It is suggested that such properties favor ion-pair formation over exciplex generation. They also enhance primary geminate recombination of initially formed (solvent-shared) ion pairs. Triplet states are generated via secondary geminate recombination of ion pairs in the membrane interior. The results bear on the general mechanism of electron transfer processes in biomembranes.

背景与目标： : 研究了荧光猝灭的动力学和一系列固定在磷脂酰胆碱小单层囊泡双层中不同深度的pyr衍生物的组织，并将其在均相溶剂系统中的行为进行了比较。研究包括基于of荧光团的振动峰表征其环境极性，以及与三个碰撞猝灭剂的相互作用: 两个膜溶猝灭剂，二乙基苯胺和溴苯以及水溶性猝灭剂碘化钾。详细表征了磷脂酰胆碱囊泡膜中二乙基苯胺-芘衍生物的系统。脂质双层和缓冲液之间的二乙基苯胺分配系数约为5,800。高达二乙基苯胺/磷脂的摩尔比1:3，对膜结构的扰动最小，因此所有光物理研究均低于该摩尔比。在所有情况下，均显示猝灭反应发生在脂质双层内部，并且各种探针分子的相对猝灭效率用于提供有关荧光探针和猝灭剂分子在脂质双层中的分布的信息。发现二乙基苯胺在脂质双层中的猝灭效率基本上与pyr部分的亚甲基链的长度无关。这些发现表明，猝灭过程是扩散控制的反应，由二乙基苯胺猝灭剂 (有效扩散系数D约为10(-7) cm2 s-1) 的迁移率决定，该迁移率似乎均匀地分布在整个脂质双层中。检查了电荷转移猝灭反应的脉冲激光光解产物。未观察到激基复合物 (激发络合物) 的形成，并且分离的自由基离子的产率比均质极性溶液小十倍。自由基离子的衰减比均匀溶液中的相应过程快得多。观察到相对较高的系统间交叉收益率。根据脂质双层的固有特性 (主要是其刚性空间组织) 来解释结果。建议这种性质比激基复合物的产生更有利于离子对的形成。它们还增强了最初形成的 (溶剂共享的) 离子对的初级重组。三重态是通过膜内部离子对的二次重组产生的。结果取决于生物膜中电子转移过程的一般机理。

BACKGROUND & AIMS: :Docetaxel (DTX), a widely prescribed anticancer agent, is now associated with increased instances of multidrug resistance. Also, being a problematic BCS class IV drug, it poses challenges for the formulators. Henceforth, it was envisioned to synthesize an analogue of DTX with a biocompatible lipid, i.e., palmitic acid. The in-silico studies (molecular docking and simulation) inferred lesser binding of docetaxel palmitate (DTX-PL) with P-gp vis-à-vis DTX and paclitaxel, indicating it to be a poor substrate for P-gp efflux. Solid lipid nanoparticles (SLNs) of the conjugate were prepared using various lipids, viz. palmitic acid, stearic acid, cetyl palmitate and glyceryl monostearate. The characterization studies for the nanocarrier were performed for the surface charge, drug payload, micromeritics, release pattern of drug and surface morphology. From the cytotoxicity assays on resistant MCF-7 cells, it was established that the new analogue offered substantially decreased IC50 to that of DTX. Further, apoptosis assay also corroborated the results obtained in IC50 determination wherein, SA-SLNs showed the highest apoptotic index than free DTX. The conjugate not only enhanced the solubility but also offered lower plasma protein binding and improved pharmacokinetic and pharmacodynamic effect for DTX loaded SA-SLNs in apt animal models, and lower affinity to P-gp efflux. The studies provide preliminary evidence and a ray of hope for a better candidate in its nano version for safer and effective cancer chemotherapy.

背景与目标： 多西紫杉醇 (DTX) 是一种广泛使用的抗癌药物，现在与多药耐药性增加有关。此外，作为一种有问题的BCS IV类药物，它给配方设计师带来了挑战。此后，设想合成具有生物相容性脂质 (即棕榈酸) 的DTX类似物。计算机研究 (分子对接和模拟) 推断多西紫杉醇棕榈酸酯 (dtx-pl) 与P-gp的结合相对于DTX和紫杉醇较小，表明它是P-gp外排的不良底物。使用各种脂质 (即棕榈酸，硬脂酸，棕榈酸十六烷基酯和单硬脂酸甘油酯) 制备缀合物的固体脂质纳米颗粒 (sln)。对纳米载体的表面电荷，药物有效载荷，微分生组织，药物的释放模式和表面形态进行了表征研究。根据对抗性MCF-7细胞的细胞毒性测定，可以确定新的类似物提供的IC50大大降低了DTX的IC50。此外，凋亡测定还证实了在IC50测定中获得的结果，其中sa-sln显示出比游离DTX最高的凋亡指数。该缀合物不仅增强了溶解度，而且还提供了较低的血浆蛋白结合，并改善了apt动物模型中DTX负载的sa-sln的药代动力学和药效学效果，并降低了对P-gp外排的亲和力。这些研究提供了初步的证据和一线希望，希望在其纳米版本中找到更安全，有效的癌症化学疗法。