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https://www.readbyqxmd.com/read/27934398/energetic-and-dynamic-analysis-of-transport-of-na-and-k-through-a-cyclic-peptide-nanotube-in-water-and-in-lipid-bilayers
#1
Yeonho Song, Ji Hye Lee, Hoon Hwang, George C Schatz, Hyonseok Hwang
Potential of mean force (PMF) profiles and position-dependent diffusion coefficients of Na(+) and K(+) are calculated to elucidate the translocation of ions through a cyclic peptide nanotube, composed of 8 × cyclo[-(d-Leu-Trp)4-] rings, in water and in hydrated DMPC bilayers. The PMF profiles and PMF decomposition analysis for the monovalent cations show that favorable interactions of the cations with the CPN as well as the lipid bilayer and dehydration free energy penalties are two major competing factors which determine the free energy surface for ion transport through CPNs both in water and in lipid bilayers, and that the selectivity of CPNs to cations mainly arises from favorable interaction energies of cations with CPNs and lipid bilayers that are more dominant than the dehydration penalties...
November 23, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27909292/crystal-structures-of-the-tric-trimeric-intracellular-cation-channel-orthologues
#2
Go Kasuya, Masahiro Hiraizumi, Andrés D Maturana, Kaoru Kumazaki, Yuichiro Fujiwara, Keihong Liu, Yoshiko Nakada-Nakura, So Iwata, Keisuke Tsukada, Tomotaka Komori, Sotaro Uemura, Yuhei Goto, Takanori Nakane, Mizuki Takemoto, Hideaki E Kato, Keitaro Yamashita, Miki Wada, Koichi Ito, Ryuichiro Ishitani, Motoyuki Hattori, Osamu Nureki
Ca(2+) release from the sarcoplasmic reticulum (SR) and endoplasmic reticulum (ER) is crucial for muscle contraction, cell growth, apoptosis, learning and memory. The trimeric intracellular cation (TRIC) channels were recently identified as cation channels balancing the SR and ER membrane potentials, and are implicated in Ca(2+) signaling and homeostasis. Here we present the crystal structures of prokaryotic TRIC channels in the closed state and structure-based functional analyses of prokaryotic and eukaryotic TRIC channels...
December 2016: Cell Research
https://www.readbyqxmd.com/read/27908266/is-metformin-a-perfect-drug-updates-in-pharmacokinetics-and-pharmacodynamics
#3
Magdalena Markowicz-Piasecka, Kristiina Maria Huttunen, Łukasz Mateusiak, Elżbieta Mikiciuk-Olasik, Joanna Sikora
Metformin, a synthetic biguanide, is currently one of the most frequently recommended medications for type 2 diabetes treatment around the world. In this review, we present the latest discoveries in the pharmacokinetics of metformin, especially the role of transporters (e.g. Organic Cation Transporters OCTs, Multidrug and Toxin Extrusion transporters MATE) in oral absorption, distribution, elimination and biochemical effects of metformin in humans. We also review the associations between genetic variations of metformin transporters, their pharmacokinetics and drug efficacy or drug responses...
December 1, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27906384/cationic-switchable-lipids-ph-triggered-molecular-switch-for-sirna-delivery
#4
W Viricel, S Poirier, A Mbarek, R M Derbali, G Mayer, J Leblond
A pH-sensitive molecular switch able to change its conformation upon protonation at endosomal pH values is embedded into the structure of cationic lipidoid materials, thus conferring endosomal escape properties. Involvement of the conformational switch in the endosomal escape process was confirmed and leading material identified was able to induce efficient gene knockdown both in vitro and in vivo. The lipid nanoparticles reported here are promising for therapeutic applications and this work could serve as a template for future design of stimulus-responsive (ionic, redox, light) molecular switch for drug and gene delivery...
December 1, 2016: Nanoscale
https://www.readbyqxmd.com/read/27905555/the-complex-nature-of-calcium-cation-interactions-with-phospholipid-bilayers
#5
Adéla Melcrová, Sarka Pokorna, Saranya Pullanchery, Miriam Kohagen, Piotr Jurkiewicz, Martin Hof, Pavel Jungwirth, Paul S Cremer, Lukasz Cwiklik
Understanding interactions of calcium with lipid membranes at the molecular level is of great importance in light of their involvement in calcium signaling, association of proteins with cellular membranes, and membrane fusion. We quantify these interactions in detail by employing a combination of spectroscopic methods with atomistic molecular dynamics simulations. Namely, time-resolved fluorescent spectroscopy of lipid vesicles and vibrational sum frequency spectroscopy of lipid monolayers are used to characterize local binding sites of calcium in zwitterionic and anionic model lipid assemblies, while dynamic light scattering and zeta potential measurements are employed for macroscopic characterization of lipid vesicles in calcium-containing environments...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27902930/modulating-micrornas-in-cardiac-surgery-patients-novel-therapeutic-opportunities
#6
REVIEW
Giovanni Biglino, Massimo Caputo, Cha Rajakaruna, Gianni Angelini, Eva van Rooij, Costanza Emanueli
This review focuses on microRNAs (miRs) in cardiac surgery, where they are emerging as potential targets for therapeutic intervention as well as novel clinical biomarkers. Identification of the up/down-regulation of specific miRs in defined groups of cardiac surgery patients can lead to the development of novel strategies for targeted treatment in order to maximise therapeutic results and minimise acute, delayed or chronic complications. MiRs could also be involved in determining the outcome independently of complications, for example in relation to myocardial perfusion and fibrosis...
November 27, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27901642/a-generic-rna-pulsed-dc-based-approach-for-developing-therapeutic-intervention-against-nasopharyngeal-carcinoma
#7
Rajeev K Tyagi, Rajesh Parmar, Naisargee Patel
The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs)...
November 30, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27901065/pharmacological-characterization-of-a-high-affinity-p-tyramine-transporter-in-rat-brain-synaptosomes
#8
Mark D Berry, Shannon Hart, Anthony R Pryor, Samantha Hunter, Danielle Gardiner
p-Tyramine is an archetypal member of the endogenous family of monoamines known as trace amines, and is one of the endogenous agonists for trace amine-associated receptor (TAAR)1. While much work has focused on the function of TAAR1, very little is known about the regulation of the endogenous agonists. We have previously reported that p-tyramine readily crosses lipid bilayers and that its release from synaptosomes is non-exocytotic. Such release, however, showed characteristics of modification by one or more transporters...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899629/enhanced-non-viral-gene-delivery-by-coordinated-endosomal-release-and-inhibition-of-%C3%AE-tubulin-deactylase
#9
Yoon Khei Ho, Li Han Zhou, Kam C Tam, Heng Phon Too
Efficient non-viral gene delivery is highly desirable but often unattainable with some cell-types. We report here that non-viral DNA polyplexes can efficiently transfect differentiated neuronal and stem cells. Polyplex transfection centrifugation protocols was enhanced by including a simultaneous treatment with a DOPE/CHEMS lipid suspension and a microtubule inhibitor, Tubastatin A. Lipoplex transfection protocols were not improved by this treatment. This mechanism of action was unravelled by systematically identifying and rationally mitigating barriers limiting high transfection efficiency, allowing unexpected improvements in the transfection of mesenchymal stem cells (MSC), primary neuron and several hard-to-transfect cell types beyond what are currently achievable using cationic polymers...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27889586/surfactant-effect-on-the-physicochemical-characteristics-of-cationic-solid-lipid-nanoparticles
#10
Chiara Botto, Nicolò Mauro, Erika Amore, Elisabetta Martorana, Gaetano Giammona, Maria Luisa Bondì
Solid lipid nanoparticles (SLNs) may be considered as a new approach for therapeutics for many diseases. In addition to drug delivery, their use as non-viral vectors for gene delivery can be obtained by including cationic lipids, which provide a positive surface potential that favors binding to the nucleic acids as DNA, siRNA, miRNA, etc. In fact, the addition of cationic surfactants is indispensable for obtaining nanoparticles with surface positive charge. In this study, three different cationic lipids (dioctadecyl dimethyl ammonium bromide, cetyltrimethyl ammonium bromide, cetylpyridinium chloride) and Brij 76 as nonionic surfactant were employed to formulate Precirol ATO 5 based cSLN using pEGFP-LUC as model plasmid...
November 23, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27884594/surface-properties-of-polyene-glycol-phospholipid-monolayers
#11
Tibor Hianik, Christer L Øpstad, Jana Šandorová, Zuzana Garaiová, Vassilia Partali, Hans-Richard Sliwka
We studied the surface properties of monolayers composed of polyunsaturated conjugated ethylene glycol phospholipids (carotenoid lipids), compared the data with monolayers of dipalmitoylphosphatidylcholine (DPPC) to which carotenoids were added and evaluated the impact of the unsaturated glycol lipids on monolayers with the glycerolipid DPPC. The carotenoid based glycol lipids formed monolayers at the air/water interface. Using the Langmuir method we obtained series of pressure-area (π-A) isotherms and determined the limiting area A per molecule of three glycol lipids, C30:9-C0A=42...
November 21, 2016: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/27877903/the-novel-functional-nucleic-acid-ired-effectively-regulates-target-genes-following-cytoplasmic-delivery-by-faint-electric-treatment
#12
Mahadi Hasan, Noriko Tarashima, Koki Fujikawa, Takashi Ohgita, Susumu Hama, Tamotsu Tanaka, Hiroyuki Saito, Noriaki Minakawa, Kentaro Kogure
An intelligent shRNA expression device (iRed) contains the minimum essential components needed for shRNA production in cells, and could be a novel tool to regulate target genes. However, general delivery carriers consisting of cationic polymers/lipids could impede function of a newly generated shRNA via electrostatic interaction in the cytoplasm. Recently, we found that faint electric treatment (fET) of cells enhanced delivery of siRNA and functional nucleic acids into the cytoplasm in the absence of delivery carriers...
2016: Science and Technology of Advanced Materials
https://www.readbyqxmd.com/read/27877134/modulation-of-the-activities-of-neuronal-ion-channels-by-fatty-acid-derived-pro-resolvents
#13
REVIEW
Geunyeol Choi, Sun Wook Hwang
Progress of inflammation depends on the balance between two biological mechanisms: pro-inflammatory and pro-resolving processes. Many extracellular and intracellular molecular components including cytokines, growth factors, steroids, neurotransmitters, and lipidergic mediators and their receptors contribute to the two processes, generated from cellular participants during inflammation. Fatty acid-derived mediators are crucial in directing the inflammatory phase and orchestrating heterogeneous reactions of participants such as inflamed cells, innate immune cells, vascular components, innervating neurons, etc...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27875623/biophysical-characterization-of-quaternary-pyridinium-functionalized-polynorbornenes-for-dna-complexation-and-their-cellular-interactions
#14
Zeliha Guler, Semra Zuhal Birol, Tarık Eren, Sebnem Ercelen Ceylan
Cationic polymers with hydrophobic side chains have gained great interest as DNA carriers since they form a compact complex with negatively charged DNA phosphate groups and interact with the cell membrane. Amphiphilic polyoxanorbornenes with different quaternary alkyl pyridinium side chains with ethyl-p(OPy2) and hexyl units-p(OPy6) bearing 10 kDa MWT were synthesized by living Ring-Opening Metathesis Polymerization method. The physicochemical characteristics: critical micellar concentration, size distribution, surface charge and condensation of polymer/DNA complex were investigated...
November 22, 2016: Biopolymers
https://www.readbyqxmd.com/read/27874109/molecular-electrometer-and-binding-of-cations-to-phospholipid-bilayers
#15
Andrea Catte, Mykhailo Girych, Matti Javanainen, Claire Loison, Josef Melcr, Markus S Miettinen, Luca Monticelli, Jukka Määttä, Vasily S Oganesyan, O H Samuli Ollila, Joona Tynkkynen, Sergey Vilov
Despite the vast amount of experimental and theoretical studies on the binding affinity of cations - especially the biologically relevant Na(+) and Ca(2+) - for phospholipid bilayers, there is no consensus in the literature. Here we show that by interpreting changes in the choline headgroup order parameters according to the 'molecular electrometer' concept [Seelig et al., Biochemistry, 1987, 26, 7535], one can directly compare the ion binding affinities between simulations and experiments. Our findings strongly support the view that in contrast to Ca(2+) and other multivalent ions, Na(+) and other monovalent ions (except Li(+)) do not specifically bind to phosphatidylcholine lipid bilayers at sub-molar concentrations...
November 30, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27874065/antimicrobial-peptide-potency-is-facilitated-by-greater-conformational-flexibility-when-binding-to-gram-negative-bacterial-inner-membranes
#16
Sarah-Beth T A Amos, Louic S Vermeer, Philip M Ferguson, Justyna Kozlowska, Matthew Davy, Tam T Bui, Alex F Drake, Christian D Lorenz, A James Mason
The interaction of antimicrobial peptides (AMPs) with the inner membrane of Gram-negative bacteria is a key determinant of their abilities to exert diverse bactericidal effects. Here we present a molecular level understanding of the initial target membrane interaction for two cationic α-helical AMPs that share structural similarities but have a ten-fold difference in antibacterial potency towards Gram-negative bacteria. The binding and insertion from solution of pleurocidin or magainin 2 to membranes representing the inner membrane of Gram-negative bacteria, comprising a mixture of 128 anionic and 384 zwitterionic lipids, is monitored over 100 ns in all atom molecular dynamics simulations...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872334/antimicrobial-peptides-mechanisms-of-action-and-resistance
#17
REVIEW
B Bechinger, S-U Gorr
More than 40 antimicrobial peptides and proteins (AMPs) are expressed in the oral cavity. These AMPs have been organized into 6 functional groups, 1 of which, cationic AMPs, has received extensive attention in recent years for their promise as potential antibiotics. The goal of this review is to describe recent advances in our understanding of the diverse mechanisms of action of cationic AMPs and the bacterial resistance against these peptides. The recently developed peptide GL13K is used as an example to illustrate many of the discussed concepts...
November 21, 2016: Journal of Dental Research
https://www.readbyqxmd.com/read/27872011/aminoclay-as-a-highly-effective-cationic-vehicle-for-enhancing-adenovirus-mediated-gene-transfer-through-nanobiohybrid-complex-formation
#18
Soo-Yeon Kim, Sang-Jin Lee, Hyo-Kyung Han, Soo-Jeong Lim
: Electrostatic complexation of adenovirus (Ad) with cationic lipids or polymers has been shown to be an effective means for overcoming the limitations of adenoviral vectors and enhancing gene-transfer efficacy. However, such complexation causes cytotoxicity, limiting the use of this strategy. The present study explored the potential of 3-aminopropyl functionalized magnesium phyllosilicate (aminoclay) as a cationic vehicle for improving Ad-mediated gene transfer without inducing cytotoxicity...
November 18, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27862758/efficient-transfection-of-sirna-by-peptide-dendrimer-lipid-conjugates
#19
Albert Kwok, Gabriela A Eggimann, Marc Heitz, Jean-Louis Reymond, Florian Hollfelder, Tamis Darbre
Efficient delivery of small interfering RNA (siRNA) into cells is the basis of target-gene-specific silencing and, ultimately, gene therapy. However, current transfection reagents are relatively inefficient, and very few studies provide the sort of systematic understanding based on structure-activity relationships that would provide rationales for their improvement. This work established peptide dendrimers (administered with cationic lipids) as siRNA transfection reagents and recorded structure-activity relationships that highlighted the importance of positive charge distribution in the two outer layers and a hydrophobic core as key features for efficient performance...
November 9, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27855891/modulation-of-chemical-stability-and-in-vitro-bioaccessibility-of-beta-carotene-loaded-in-kappa-carrageenan-oil-in-gel-emulsions
#20
Christos Soukoulis, Maria Tsevdou, Christelle M Andre, Sébastien Cambier, Lina Yonekura, Petros S Taoukis, Lucien Hoffmann
In the present paper, ionotropically structured κ-carrageenan based oil-in-gel (o/g) emulsions were tested as potential carrier systems for the delivery of β-carotene. In situ ionic gelation was induced by Na(+), K(+) or Ca(2+) added at the level of 0.2-0.6% (w/w). All o/g emulsions exerted a true gel like behaviour with storage modulus (G') being reduced according to the order: K(+)>Ca(2+)>Na(+). Ionic gelation induced a moderate increase in the microscopically assessed lipid droplets radii. O/g emulsions containing monovalent ions exerted the highest β-carotene retention throughout isothermal storage particularly at high (37 and 55°C) temperatures...
April 1, 2017: Food Chemistry
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