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Yang Li, Huabing Zhang, Yilin Chen, Jinyuan Ma, Jinyan Lin, Yinying Zhang, Zhongxiong Fan, Guanghao Su, Liya Xie, Xuan Zhu, Zhenqing Hou
Combinational cancer therapy has been considered as a promising strategy to achieve synergetic therapeutic effects and suppression of multidrug resistance. Herein, we adopted a combination of methotrexate (MTX), an antimetabolite acting on cytoplasm, and 10-hydroxycamptothecin (HCPT), an alkaloid acting on nuclei, to treat cancer. Given the different solubilities, membrane permeabilities, and anticancer mechanisms of both drugs, we developed a dual-targeting delivery system based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-hyaluronic acid (a principal ligand of CD44 receptors)-MTX (a selective ligand of folate receptors) nanoparticles, which was exploited to carry HCPT-MTX conjugate for synergistically boosting dual-drug co-delivery...
May 22, 2018: Biomaterials Science
Weihua Chen, Hooman Salari, Matthew C Taylor, Ricarda Jost, Oliver Berkowitz, Russell Barrow, Deyun Qiu, Remi Branco, Josette Masle
Phosphatidylcholine (PC) is a major membrane phospholipid and a precursor for most signalling molecules. Understanding its synthesis is important for improving plant growth, nutritional value and resistance to stress. PC synthesis is complex, involving several interconnected pathways, one of which proceeds from serine-derived phosphoethanolamine (PEA) to form phosphocholine (PCho) through three sequential phospho-base methylations catalysed by phosphoethanolamine N-methyltransferases (PEAMTs). The contribution of this pathway to the production of PC and plant growth has been a matter of some debate...
May 18, 2018: Plant Physiology
Adarsh K Chaurasia, Andrew M Rukangu, Michael K Philen, Gary D Seidel, Eric C Freeman
In the current paper, phospholipid bilayers are modeled using coarse-grained molecular dynamics simulations with the MARTINI force field. The extracted molecular trajectories are analyzed using Fourier analysis of the undulations and orientation vectors to establish the differences between the two approaches for evaluating the bending modulus. The current work evaluates and extends the implementation of the Fourier analysis for molecular trajectories using a weighted horizon-based averaging approach. The effect of numerical parameters in the analysis of these trajectories is explored by conducting parametric studies...
March 2018: Physical Review. E
Xinggui Gu, Xiaoyan Zhang, Huili Ma, Shaorui Jia, Pengfei Zhang, Yanjun Zhao, Qian Liu, Jianguo Wang, Xiaoyan Zheng, Jacky W Y Lam, Dan Ding, Ben Zhong Tang
Fluorescent nanoparticles (NPs) based on luminogens with aggregation-induced emission characteristic (AIEgens), namely AIE dots, have received wide attention because of their antiquenching attitude in emission and reactive oxygen species (ROS) generation when aggregated. However, few reports are available on how to control and optimize their fluorescence and ROS generation ability. Herein, it is reported that enhancing the intraparticle confined microenvironment is an effective approach to advanced AIE dots, permitting boosted cancer phototheranostics in vivo...
May 16, 2018: Advanced Materials
Wenhui Wei, Swaminath Srinivas, Jingxia Lin, Zichen Tang, Shihua Wang, Saif Ullah, Vishnu Goutham Kota, Youjun Feng
Polymyxin is the last line of defense against severe infections caused by carbapenem-resistant gram-negative pathogens. The emergence of transferable MCR-1/2 polymyxin resistance greatly challenges the renewed interest in colistin (polymyxin E) for clinical treatments. Recent studies have suggested that Moraxella species are a putative reservoir for MCR-1/2 genetic determinants. Here, we report the functional definition of ICR-Mo from M. osloensis, a chromosomally encoded determinant of colistin resistance, in close relation to current MCR-1/2 family...
May 14, 2018: PLoS Genetics
O Kereilwe, K Pandey, H Kadokawa
We recently discovered that the orphan G-protein-coupled receptor (GPR) 61 colocalized with GnRH receptors (GnRHRs) on the surface of most of bovine gonadotrophs. A recent study suggested that ethanolamine plasmalogen (PI) is a ligand for GPR61 in mouse neuroblastoma. Therefore, this study evaluated the hypothesis that PI alters LH and FSH secretion from cultured bovine anterior pituitary (AP) cells. We prepared bovine AP cells from postpubertal heifers (26 mo old) and cultured the cells for 3.5 d. We treated the cells with increasing concentrations (0, 5, 50, 500, 5,000, 50,000, or 500,000 pg/mL) of phosphoethanolamine PI (PEPI) extracted from the bovine brain, or l-α-lysophosphatidylethanolamine PI (LEPI) extracted from the bovine brain, for 5 min before either no treatment or GnRH stimulation...
April 10, 2018: Domestic Animal Endocrinology
Yu Luo, Muhammad Afzal Javed, Harry Deneer, Xialu Chen
Bacteria inhabit a vast range of biological niches and have evolved diverse mechanisms to cope with environmental stressors. The genus Acinetobacter comprises a complex group of Gram-negative bacteria. Some of these bacteria such as A. baumannii are nosocomial pathogens. They are often resistant to multiple antibiotics and are associated with epidemic outbreaks. A. radioresistens is generally considered to be a commensal bacterium on human skin or an opportunistic pathogen. Interestingly, this species has exceptional resistance to a range of environmental challenges which contributes to its persistence in clinical environment and on human skin...
May 10, 2018: Scientific Reports
Xinyu Hong, H Deborah Chen, Eduardo A Groisman
Lipid A is the innermost component of the lipopolysaccharide (LPS) molecules that occupy the outer leaflet of the outer membrane in Gram-negative bacteria. Lipid A is recognized by the host immune system and targeted by cationic antimicrobial compounds. In Salmonella enterica serovar Typhimurium, the phosphates of lipid A are chemically modified by enzymes encoded by targets of the transcriptional regulator PmrA. These modifications increase resistance to the cationic peptide antibiotic polymyxin B by reducing the negative charge of the LPS...
May 8, 2018: Science Signaling
Tomoyuki Nishizaki
BACKGROUND/AIMS: Phosphatidylethanolamine, a component of the plasma membrane, regulates diverse cellular processes. The present study investigated the role of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in the trafficking of the glucose transporter GLUT4 and the glucose homeostasis. METHODS: Monitoring of GLUT4 trafficking, GLUT4 internalization assay, and glucose uptake assay were carried out using differentiated 3T3-L1-GLUT4myc adipocytes. Akt1/2 and PKC isozymes were knocked-down by transfecting each siRNA...
April 26, 2018: Cellular Physiology and Biochemistry
Deanna Deveson Lucas, Bethany Crane, Amy Wright, Mei-Ling Han, Jennifer Moffatt, Dieter Bulach, Simon L Gladman, David Powell, Jesus Aranda, Torsten Seemann, Diana Machado, Teresa Pacheco, Teresa Marques, Miguel Viveiros, Roger Nation, Jian Li, Marina Harper, John D Boyce
Colistin is a crucial last-line drug used for the treatment of life-threatening infections caused by multi-drug resistant strains of the Gram-negative bacteria, Acinetobacter baumannii However, colistin-resistant A. baumannii isolates can be isolated following failed colistin therapy. Resistance is most often mediated by the addition of phosphoethanolamine (pEtN) to lipid A by PmrC, following missense mutations in the pmrCAB operon encoding PmrC and the two-component signal transduction system PmrA/PmrB. We recovered a pair of A...
April 30, 2018: Antimicrobial Agents and Chemotherapy
Nicolas Kieffer, Patrice Nordmann, Andrea Micke Moreno, Luisa Zanolli Moreno, Richard Chaby, Aude Breton, Pierre Tissières, Laurent Poirel
A collection of 126 pigs were screened for carriage of colistin-resistant Enterobacteriaceae in a farm in Minas Gerais, Brazil. Out of this collection, eigth colistin-resistant Escherichia coli isolates were recovered, including one from Minas Gerais State, producing a new MCR-3 variant (MCR-3.12). Analysis of the lipopolysaccharide revealed that MCR-3.12 had a similar function as MCR-1 and MCR-2 by adding a phosphoethanolamine group to the lipid A. Genetic analysis showed that the mcr-3.12 gene was carried by an IncA/C2 plasmid and was embedded in an original genetic environment...
April 30, 2018: Antimicrobial Agents and Chemotherapy
Nai-Jia Huang, Ying-Cing Lin, Chung-Yueh Lin, Novalia Pishesha, Caroline A Lewis, Elizaveta Freinkman, Colin Farquharson, José Luis Millán, Harvey Lodish
Red cells contain a unique constellation of membrane lipids. While much is known about regulated protein expression, the regulation of lipid metabolism during erythropoiesis is poorly studied. Here we show that transcription of PHOSPHO1, a phosphoethanolamine and phosphocholine phosphatase that mediates the hydrolysis of phosphocholine to choline, is strongly upregulated during the terminal stages of erythropoiesis of both human and mouse erythropoiesis, concomitant with increased catabolism of phosphatidylcholine and phosphocholine as shown by global lipidomic analyses of mouse and human terminal erythropoiesis...
April 30, 2018: Blood
Esteban N Lorenzón, Thatyane M Nobre, Luciano Caseli, Eduardo M Cilli, Gabriel C A da Hora, Thereza A Soares, Osvaldo N Oliveira
Antimicrobial peptides (AMPs) are alternatives to conventional antibiotics against multi-drug resistant bacteria with low potential for developing microbial resistance. The design of such molecules requires understanding of the mechanisms of action, particularly the interaction with bacteria cell membranes. In this work, we determine the mechanism responsible for the higher activity against Escherichia coli of the C-terminal lysine dimer of magainin 2, (MG2)2 K, in comparison to the monomeric peptide magainin 2 (MG2)...
April 20, 2018: Colloids and Surfaces. B, Biointerfaces
Yasunori Uemura, Tomoyuki Naoi, Yasumasa Kanai, Katsuya Kobayashi
Small interfering of RNA (siRNA) technology has the potential to be a next-generation therapy. However, naked siRNA does not have high transfection efficiency and is rapidly degraded after systemic injection, so an appropriate drug delivery system (DDS) is required for clinical use. Several potential systems have been assessed, clinically focusing on hepatocyte or cancer tissue using siRNA. However, targeting immune cells using siRNA is still challenging, and a new DDS is required. In this study, we prepared lipid nanoparticles (LNP) composed of original cationic lipid, neutral lipid of DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and PEG2000-DMPE (N- (Carbonyl-methoxypolyethyleneglycol 2000) -1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, sodium salt)...
April 24, 2018: Pharmaceutical Development and Technology
Luis M Guachalla, Katharina Ramoni, Cecilia Varga, Michele Mutti, Akela Ghazawi, Tibor Pál, Eszter Nagy, Ágnes Sonnevend, Gábor Nagy, Valéria Szijártó
Plasmid-encoded colistin resistance is emerging among extra-intestinal pathogenic Escherichia coli including the epidemic clone ST131-H30. Mcr-1 transfers a phosphoethanolamine to the lipid A portion of LPS conferring resistance to polymyxins. We investigated whether this modification changed the activity of the monoclonal antibody, ASN-4 specific to the O25b side-chain of ST131 LPS. We confirmed that, unlike colistin, ASN-4 retained its bactericidal and endotoxin neutralizing activity and therefore offer a treatment option against extremely drug-resistant ST131 isolates...
April 23, 2018: Antimicrobial Agents and Chemotherapy
Foteini Papageorgiou, Natassa Pippa, Nikolaos Naziris, Costas Demetzos
The aim of the present study is to investigate the interactions between liposomes and proteins and to evaluate the role of liposomal lipid composition and concentration in the formation of protein corona. Liposomes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or hydrogenated soybean phosphatidylcholine (HSPC) with 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DPPG), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000] (DPPE-PEG 3000), cholesterol (CH) or mixtures of these lipids, were prepared at different concentrations by the thin-film hydration method...
April 24, 2018: Journal of Liposome Research
Jaroslaw Piskorz, Dariusz T Mlynarczyk, Wojciech Szczolko, Krystyna Konopka, Nejat Düzgüneş, Jadwiga Mielcarek
Photodynamic therapy of cancer comprises the activation of photosensitizer molecules delivered to cancer cells, to generate reactive oxygen species that mediate cytotoxicity. In this study, previously synthesized dendritic magnesium tribenzoporphyrazines were incorporated into four types of liposomes containing either 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as the zwitterionic lipids. The addition of either l-α-phosphatidyl-dl-glycerol (PG) or 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) imparted a negative or positive charge, respectively...
April 9, 2018: Journal of Inorganic Biochemistry
Xudong Fu, Yuanyuan Lu, Jiaping Guo, Hui Liu, Aiping Deng, Changchun Kuang, Xiangyang Xie
This study aimed to develop novel temperature-sensitive liposomes loading paclitaxel (PTX-TSL) and evaluate them in vitro to improve the delivery efficiency and targeting of PTX. K237 peptide was conjugated to the terminal NHS of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol)-(DSPE-PEG-NHS), and K237-modified PTX-TSL (K237-PTX-TSL) was prepared using a film dispersion method. K237-TSL encapsulation with calcein was synthesized and used to determine the cellular uptake of TSL...
April 19, 2018: Journal of Liposome Research
Xin Xin Zhou, Long Jin, Rui Qun Qi, Teng Ma
In the present study, a novel pH-responsive amphiphilic copolymer, 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[methoxy(polyethylene glycol)] conjugated poly(β-amino esters) (DSPE- b -PEG- b -PAE- b -PEG- b -DSPE), was designed and successfully synthesized via Michael-type step polymerization. The chemical structure of the pentablock copolymer was confirmed with proton nuclear magnetic resonance (1 H-NMR) and Fourier transform infrared (FT-IR) spectroscopy. The copolymer was able to self-assemble into core/shell polymeric micelles in aqueous solution at low concentrations, and its critical micelle concentration (CMC) value was 4...
March 2018: Royal Society Open Science
Venkanna Muripiti, Hari Krishnareddy Rachamalla, Rajkumar Banerjee, Srilakshmi V Patri
Endosomal escape is one of the barriers for the efficient liposomal gene delivery. To address this and based on earlier encouraging results using tocopherol cationic lipids, we elaborated chemical modifications on tocopherol cationic lipids by introducing a novel hybrid pH sensitive linker "ether-β-hydroxy-triazole" between tocopherol, the anchoring moiety and the basic tris(2-hydroxy ethyl)quaternary ammonium head group (Lp2). As control lipids we designed two lipids (Lp1 and Lp3), one is with only the ether-β-hydroxy linker in between α-tocopherol and quaternary tris(2-hydroxyethyl)ammonium (Lp1) and the other is with the same novel hybrid linker i...
April 6, 2018: Organic & Biomolecular Chemistry
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