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https://www.readbyqxmd.com/read/28731321/conjugation-dependent-interaction-of-folic-acid-with-folate-binding-protein
#1
Rachel Leah Merzel, Carolina Frey, Junjie Chen, Rachel Garn, Mallory A van Dongen, Casey A Dougherty, Ananda Kandaluru, Philip S Low, E Neil G Marsh, Mark M Banaszak Holl
Serum proteins play a critical role in the transport, uptake, and efficacy of targeted drug therapies, and here we investigate the interactions between folic acid-polymer conjugates and serum folate binding protein (FBP), the soluble form of the cellular membrane-bound folate receptor. We demonstrate that both choice of polymer and method of ligand conjugation affect the interactions between folic acid-polymer conjugates and serum FBP, resulting in changes in the folic acid-induced protein aggregation process...
July 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28731269/biofilm-formation-and-antibiotic-resistance-in-klebsiella-pneumoniae-urinary-strains
#2
Claudia Vuotto, Francesca Longo, Chiara Pascolini, Gianfranco Donelli, Maria Pia Balice, Maria Francesca Libori, Valentina Tiracchia, Antonino Salvia, Pietro Emanuele Varaldo
AIMS: Multi-drug resistant Klebsiella pneumoniae has become a relevant healthcare-associated pathogen. Capsule, type 1 and 3 fimbriae (mrkA gene), type 2 quorum-sensing system (luxS), synthesis of D-galactan I (wbbM), LPS transport (wzm) and poly-beta-1,6-N-acetyl-D-glucosamine (pgaA) seem involved in K. pneumoniae biofilm. Non-enzymatic antibiotic resistance is related to non-expression or mutation of porins (OmpK35 and OmpK36), and efflux pump (acrB) over-expression. The aim of this study was to analyse some virulence factors of K...
July 21, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28730961/novel-fluorinated-porphyrins-sensitize-tumor-cells-to-photodamage-in-normoxia-and-hypoxia-synthesis-and-biocompatible-formulations
#3
Elizaveta V Belyaeva, Alina A Markova, Dmitry N Kaluzhnyb, Andrei L Sigan, Lev L Gervitz, Aida N Ataeva, Nikolai D Chkanikov, Alexander A Shtil
: Background. Hypoxia renders tumor cells refractory to treatment. One way to overcome this problem is the design of drug delivery systems that contain the antitumor agent within an oxygen supply medium. OBJECTIVE: to evaluate whether the perfluorocarbon liquids (capable of retaining up to 50% v/v amounts of O2 gas) can be tools for delivery of photosensitizers to hypoxic tumors. METHOD: We synthesized a series of compounds in which fluoroaliphatic or fluoroaromatic moieties were conjugated to the porphyrin ring in meso-positions...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28730938/stratum-corneum-modulation-by-chemical-enhancers-and-lipid-nanostructures-implications-for-transdermal-drug-delivery
#4
Mudra Saurabh Kapoor, Shruti GuhaSarkar, Rinti Banerjee
Skin is the outermost and largest protective covering of the body. The uppermost layer of the skin, stratum corneum also called the horny layer is composed of keratin-filled cells covered by a lipid matrix which shields the skin from physical and chemical entrants. The lipid lamellar structure comprises of ceramides, cholesterol, fatty acids and proteins. Chemical enhancers that mimic the lamellar chemistry, reversibly fluidize the latter can be utilized for enhancing transport of cargo across the epidermis into the dermis...
July 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28730856/in-vitro-drug-drug-interactions-of-budesonide-inhibition-and-induction-of-transporters-and-cytochrome-p450-enzymes
#5
Nancy Chen, Donghui Cui, Qing Wang, Zhiming Wen, Richard D Finkelman, Devin Welty
1. Budesonide is a glucocorticoid used in the treatment of several respiratory and gastrointestinal inflammatory diseases. Glucocorticoids have been demonstrated to induce cytochrome P450 (CYP) 3A and the efflux transporter P-glycoprotein (P-gp). This study aimed to evaluate the potential of budesonide to act as a perpetrator or a victim of transporter- or CYP-mediated drug-drug interactions (DDIs). 2. In vitro studies were conducted for P-gp, breast cancer resistance protein and organic anion and cation transporters (OATP1B1, OATP1B3, OAT1, OAT3, OCT2) in transporter-transfected cells...
July 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28730152/zebrafish-get-connected-investigating-neurotransmission-targets-and-alterations-in-chemical-toxicity
#6
Katharine A Horzmann, Jennifer L Freeman
Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio) model system is increasingly being used to study the brain and chemical neurotoxicity. In this review, the major neurotransmitter systems, including glutamate, GABA, dopamine, norepinephrine, serotonin, acetylcholine, histamine, and glutamate are surveyed and pathways of synthesis, transport, metabolism, and action are examined...
September 2016: Toxics
https://www.readbyqxmd.com/read/28729850/drug-resistant-epilepsy-multiple-hypotheses-few-answers
#7
REVIEW
Fei Tang, Anika M S Hartz, Björn Bauer
Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28729424/molecular-determinants-of-acidic-ph-dependent-transport-of-human-equilibrative-nucleoside-transporter-3
#8
Md Fazlur Rahman, Candice Askwith, Rajgopal Govindarajan
Equilibrative nucleoside transporters (ENTs) translocate hydrophilic nucleosides across cellular membranes and are essential for salvage nucleotide synthesis and purinergic signaling. Unlike the prototypic human ENT members hENT1 and hENT2, which mediate plasma membrane nucleoside transport at pH 7.4, hENT3 is an acidic pH-activated lysosomal transporter partially localized to mitochondria. Recent studies demonstrate that hENT3 is indispensable for lysosomal homeostasis, and that mutations in hENT3 can result in a spectrum of lysosomal storage-like disorders...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28729070/abc-transporters-in-the-liver-fluke-opisthorchis-felineus
#9
Viatcheslav A Mordvinov, Nikita I Ershov, Darya S Pirozhkova, Yuri V Pakharukov, Maria Y Pakharukova
ATP-binding cassette transporters (ABC transporters) are essential components of normal cellular physiological machinery in all eukaryotic and prokaryotic species, including parasites. Some ABC transporters, e.g., P-glycoproteins, are involved in the efflux of toxins and xenobiotics from the cell. At present, nothing is known about ABC transporter genes in epidemiologically important liver flukes from the Opisthorchiidae family, including European liver fluke Opisthorchis felineus. Opisthorchiasis caused by O...
July 17, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28728917/global-alteration-of-the-drug-binding-pocket-of-human-p-glycoprotein-abcb1-by-substitution-of-fifteen-conserved-residues-reveals-a-negative-correlation-between-substrate-size-and-transport-efficiency
#10
Shahrooz Vahedi, Eduardo E Chufan, Suresh V Ambudkar
P-glycoprotein (P-gp), an ATP-dependent efflux pump, is linked to the development of multidrug resistance in cancer cells. However, the drug-binding sites and translocation pathways of this transporter are not yet well-characterized. We recently demonstrated the important role of tyrosine residues in regulating P-gp ATP hydrolysis via hydrogen bond formations with high affinity modulators. Since tyrosine is both a hydrogen bond donor and acceptor, and non-covalent interactions are key in drug transport, in this study we investigated the global effect of enrichment of tyrosine residues in the drug-binding pocket on the drug binding and transport of P-gp...
July 17, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28727843/atomistic-modeling-of-alternating-access-of-a-mitochondrial-adp-atp-membrane-transporter-with-molecular-simulations
#11
Koichi Tamura, Shigehiko Hayashi
The mitochondrial ADP/ATP carrier (AAC) is a membrane transporter that exchanges a cytosolic ADP for a matrix ATP. Atomic structures in an outward-facing (OF) form which binds an ADP from the intermembrane space have been solved by X-ray crystallography, and revealed their unique pseudo three-fold symmetry fold which is qualitatively different from pseudo two-fold symmetry of most transporters of which atomic structures have been solved. However, any atomic-level information on an inward-facing (IF) form, which binds an ATP from the matrix side and is fixed by binding of an inhibitor, bongkrekic acid (BA), is not available, and thus its alternating access mechanism for the transport process is unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28727483/pharmacological-treatment-of-tardive-dyskinesia-recent-developments
#12
Stanley N Caroff, E Cabrina Campbell, Benjamin Carroll
Tardive dyskinesia (TD) occurs in patients receiving antipsychotic treatment with dopamine receptor antagonists. Despite the prevalence of TD and its negative impact on patients' lives, there has been a lack of approved treatments and limited evidence from controlled trials of pharmacological treatment. Areas covered: PubMed was searched for English-language papers published during 2007-2016 using terms "tardive dyskinesia" or "drug-induced movement disorder", and "treatment". Studies evaluating pharmacological agents for the treatment of TD were selected...
July 20, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28726848/patch-clamp-technique-to-characterize-ion-channels-in-enlarged-individual-endolysosomes
#13
Cheng-Chang Chen, Chunlei Cang, Stefanie Fenske, Elisabeth Butz, Yu-Kai Chao, Martin Biel, Dejian Ren, Christian Wahl-Schott, Christian Grimm
According to proteomics analyses, more than 70 different ion channels and transporters are harbored in membranes of intracellular compartments such as endosomes and lysosomes. Malfunctioning of these channels has been implicated in human diseases such as lysosomal storage disorders, neurodegenerative diseases and metabolic pathologies, as well as in the progression of certain infectious diseases. As a consequence, these channels have engendered very high interest as future drug targets. Detailed electrophysiological characterization of intracellular ion channels is lacking, mainly because standard methods to analyze plasma membrane ion channels, such as the patch-clamp technique, are not readily applicable to intracellular organelles...
August 2017: Nature Protocols
https://www.readbyqxmd.com/read/28726801/accumbens-mechanisms-for-cued-sucrose-seeking
#14
Ana-Clara Bobadilla, Constanza Garcia-Keller, Jasper A Heinsbroek, Michael Scofield, Victoria Chareunsouk, Cara Monforton, Peter W Kalivas
Many studies support a perspective that addictive drugs usurp brain circuits used by natural rewards, especially for the dopamine-dependent reinforcing qualities of both drugs and natural rewards. Reinstated drug seeking in animal models of relapse relies on glutamate spillover from cortical terminals synapsing in the nucleus accumbens core (NAcore) to stimulate metabotropic glutamate receptor5 (mGluR5) on neuronal nitric oxide synthase (nNOS) interneurons. Contrasting the release of dopamine that is shared by sucrose and drugs of abuse, reinstated sucrose seeking does not induce glutamate spillover...
July 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28726349/aspherical-nanostructured-microparticles-for-targeted-gene-delivery-to-alveolar-macrophages
#15
Michael Möhwald, Shashank Reddy Pinnapireddy, Bodo Wonnenberg, Marcel Pourasghar, Marijas Jurisic, Andrea Jung, Claudia Fink-Straube, Thomas Tschernig, Udo Bakowsky, Marc Schneider
Introducing novel shapes to particulate carrier systems adds unique features to modern drug and gene delivery. Depending on the route of administration, particle geometry can influence deposition and fate within biological environments. In this work, a template-assisted engineering technique is applied, providing full control of size and shape in the preparation of aspherical, nanostructured microparticles. Based on the interconnection of nanoparticles, stabilized by a functional layer-by-layer (LbL) coating, the resulting cylindrical micrometer architecture is especially qualified for pulmonary delivery...
July 20, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28726099/lipoxygenases-modulate-the-effect-of-glutoxim-on-na-transport-in-the-frog-skin-epithelium
#16
Z I Krutetskaya, A V Melnitskaya, V G Antonov, A D Nozdrachev
Using voltage-clamp technique, the involvement of lipoxygenases in the effect of immunomodulatory drug glutoxim on Na(+) transport in frog skin was investigated. It was shown for the first time that preincubation of the skin with lipoxygenase inhibitors caffeic acid, baicalein, and nordihydroguaiaretic acid significantly decreases the stimulatory effect of glutoxim on Na(+) transport. The data suggest the involvement of lipoxygenase oxidation pathway of arachidonic acid metabolism in the glutoxim effect on Na(+) transport in frog skin epithelium...
May 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28725901/zinc-binding-sites-in-pra1-a-zincophore-from-candida-albicans
#17
Dorota Łoboda, Magdalena Rowińska-Żyrek
The aim of this work is to understand the interactions of Zn(ii) with Pra1, a zincophore from Candida albicans, one of the most common causes of serious fungal infections in humans. Pra1 is a 299 amino acid protein, secreted from the fungus to specifically bind Zn(ii) and deliver it to a transmembrane zinc transporter, Zrt1. We take the first step towards understanding the bioinorganic chemistry of this process, by pointing out the Zn(ii) binding sites in Pra1 and understanding the thermodynamics of such interactions...
July 20, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28725634/ip3-receptor-mediated-calcium-signaling-and-its-role-in-autophagy-in-cancer
#18
REVIEW
Elzbieta Kania, Gemma Roest, Tim Vervliet, Jan B Parys, Geert Bultynck
Calcium ions (Ca(2+)) play a complex role in orchestrating diverse cellular processes, including cell death and survival. To trigger signaling cascades, intracellular Ca(2+) is shuffled between the cytoplasm and the major Ca(2+) stores, the endoplasmic reticulum (ER), the mitochondria, and the lysosomes. A key role in the control of Ca(2+) signals is attributed to the inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), the main Ca(2+)-release channels in the ER. IP3Rs can transfer Ca(2+) to the mitochondria, thereby not only stimulating core metabolic pathways but also increasing apoptosis sensitivity and inhibiting basal autophagy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28725218/all-new-faces-of-diatoms-potential-source-of-nanomaterials-and-beyond
#19
REVIEW
Meerambika Mishra, Ananta P Arukha, Tufail Bashir, Dhananjay Yadav, G B K S Prasad
Nature's silicon marvel, the diatoms have lately astounded the scientific community with its intricate designs and lasting durability. Diatoms are a major group of phytoplanktons involved in the biogeochemical cycling of silica and are virtually inherent in every environment ranging from water to ice to soil. The usage of diatoms has proved prudently cost effective and its handling neither requires costly materials nor sophisticated instruments. Diatoms can easily be acquired from the environment, their culture requires ambient condition and does not involve any costly media or expensive instruments, besides, they can be transported in small quantities and proliferated to a desirable confluence from that scratch, thus are excellent cost effective industrial raw material...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28724771/intracellular-colocalization-of-influenza-viral-rna-and-rab11a-is-dependent-upon-microtubule-filaments
#20
Eric Nturibi, Amar R Bhagwat, Stefanie Coburn, Mike M Myerburg, Seema S Lakdawala
Influenza A virus (IAV) consists of eight viral RNA (vRNA) segments that are replicated in the host cell nucleus and transported to the plasma membrane for packaging into progeny virions. We have previously proposed a model where sub-complexes of vRNA export from the nucleus and assemble en route to the plasma membrane. However, the role of host cytoskeletal proteins in the cytoplasmic assembly of IAV vRNA segments remains unknown. Previous studies have suggested that IAV vRNA segments transport via Rab11A-containing recycling endosomes (RE) and use both microtubules (MT) and actin...
July 19, 2017: Journal of Virology
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