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https://www.readbyqxmd.com/read/28214518/potentiating-slc-transporter-activity-emerging-drug-discovery-opportunities
#1
REVIEW
Marie-Laure Rives, Jonathan A Javitch, Alan D Wickenden
Maintaining the integrity of cellular membranes is critical to protecting metabolic activities and genetic information from the environment. Regulation of transport across membranes of essential chemicals, including water, nutrients, hormones and many drugs, is therefore key to cellular homeostasis and physiological processes. The two main transporter superfamilies are ATP-binding cassette (ABC) transporters that primarily function as efflux transporters, and the solute carrier (SLC) transporters. SLC transporters encompass 52 gene families with almost 400 different human transporter genes...
February 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28212401/preload-based-starling-like-control-of-rotary-blood-pumps-an-in-vitro-evaluation
#2
Mahdi Mansouri, Shaun D Gregory, Robert F Salamonsen, Nigel H Lovell, Michael C Stevens, Jo P Pauls, Rini Akmeliawati, Einly Lim
Due to a shortage of donor hearts, rotary left ventricular assist devices (LVADs) are used to provide mechanical circulatory support. To address the preload insensitivity of the constant speed controller (CSC) used in conventional LVADs, we developed a preload-based Starling-like controller (SLC). The SLC emulates the Starling law of the heart to maintain mean pump flow ([Formula: see text]) with respect to mean left ventricular end diastolic pressure (PLVEDm) as the feedback signal. The SLC and CSC were compared using a mock circulation loop to assess their capacity to increase cardiac output during mild exercise while avoiding ventricular suction (marked by a negative PLVEDm) and maintaining circulatory stability during blood loss and severe reductions in left ventricular contractility (LVC)...
2017: PloS One
https://www.readbyqxmd.com/read/28188910/expression-and-splicing-of-abc-and-slc-transporters-in-the-human-blood-brain-barrier-measured-with-rnaseq
#3
Adam M Suhy, Amy Webb, Audrey C Papp, Ethan G Geier, Wolfgang Sadee
The blood-brain barrier (BBB) expresses numerous membrane transporters that supply needed nutrients to the central nervous system (CNS), consisting mostly of solute carriers (SLC transporters), or remove unwanted substrates via extrusion pumps through the action of ATP binding cassette (ABC) transporters. Previous work has identified many BBB transporters using hybridization arrays or qRT-PCR, using targeted probes. Here we have performed next-generation sequencing of the transcriptome (RNAseq) extracted from cerebral cortex tissues and brain microvessel endothelial cells (BMEC) obtained from two donors...
February 7, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28178198/zinc-transporter-3-znt3-in-the-enteric-nervous-system-of-the-porcine-ileum-in-physiological-conditions-and-during-experimental-inflammation
#4
Sławomir Gonkowski, Maciej Rowniak, Joanna Wojtkiewicz
Zinc transporter 3 (ZnT3) is a member of the solute-linked carrier 30 (SLC 30) zinc transporter family. It is closely linked to the nervous system, where it takes part in the transport of zinc ions from the cytoplasm to the synaptic vesicles. ZnT3 has also been observed in the enteric nervous system (ENS), but its reactions in response to pathological factors remain unknown. This study, based on the triple immunofluorescence technique, describes changes in ZnT3-like immunoreactive (ZnT3-LI) enteric neurons in the porcine ileum, caused by chemically-induced inflammation...
February 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28176814/eunag-a-new-ligand-inducible-fluorescent-reporter-to-detect-drug-transporter-activity-in-live-cells
#5
Johannes T-H Yeh, Kwangho Nam, Joshua T-H Yeh, Norbert Perrimon
The absorption, distribution, metabolism and excretion (ADME) of metabolites and toxic organic solutes are orchestrated by the ATP-binding cassette (ABC) transporters and the organic solute carrier family (SLC) proteins. A large number of ABC and SLC transpoters exist; however, only a small number have been well characterized. To facilitate the analysis of these transporters, which is important for drug safety and physiological studies, we developed a sensitive genetically encoded bilirubin (BR)-inducible fluorescence sensor (eUnaG) to detect transporter-coupled influx/efflux of organic compounds...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174690/the-gene-expression-of-numerous-slc-transporters-is-altered-in-the-immortalized-hypothalamic-cell-line-n25-2-following-amino-acid-starvation
#6
Sofie V Hellsten, Emilia Lekholm, Tauseef Ahmad, Robert Fredriksson
Amino acids are known to play a key role in gene expression regulation, and in mammalian cells, amino acid signaling is mainly mediated via two pathways, the mammalian target of rapamycin complex 1 (mTORC1) pathway and the amino acid responsive (AAR) pathway. It is vital for cells to have a system to sense amino acid levels, in order to control protein and amino acid synthesis and catabolism. Amino acid transporters are crucial in these pathways, due to both their sensing and transport functions. In this large-scale study, an immortalized mouse hypothalamic cell line (N25/2) was used to study the gene expression changes following 1, 2, 3, 5 or 16 h of amino acid starvation...
February 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28153036/biomechanical-comparison-of-multilevel-lateral-interbody-fusion-with-and-without-supplementary-instrumentation-a-three-dimensional-finite-element-study
#7
Xilin Liu, Jun Ma, Paul Park, Xiaodong Huang, Ning Xie, Xiaojian Ye
BACKGROUND: Lateral lumbar interbody fusion (LLIF) is a popular, minimally invasive technique that is used to address challenging multilevel degenerative spinal diseases. It remains controversial whether supplemental instrumentation should be added for multilevel LLIF. In this study, we compared the kinematic stability afforded by stand-alone lateral cages with those supplemented by bilateral pedicle screws and rods (PSR), unilateral PSR, or lateral plate (LP) fixation using a finite-element (FE) model of a multi-level LLIF construct with simulated osteoporosis...
February 2, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28113872/quantum-ensemble-classification-a-sampling-based-learning-control-approach
#8
Chunlin Chen, Daoyi Dong, Bo Qi, Ian R Petersen, Herschel Rabitz
Quantum ensemble classification (QEC) has significant applications in discrimination of atoms (or molecules), separation of isotopes, and quantum information extraction. However, quantum mechanics forbids deterministic discrimination among nonorthogonal states. The classification of inhomogeneous quantum ensembles is very challenging, since there exist variations in the parameters characterizing the members within different classes. In this paper, we recast QEC as a supervised quantum learning problem. A systematic classification methodology is presented by using a sampling-based learning control (SLC) approach for quantum discrimination...
March 23, 2016: IEEE Transactions on Neural Networks and Learning Systems
https://www.readbyqxmd.com/read/28112518/lc-ms-ms-based-quantitation-of-abc-and-slc-transporter-proteins-in-plasma-membranes-of-cultured-primary-human-retinal-pigment-epithelium-cells-and-immortalized-arpe19-cell-line
#9
Laura Pelkonen, Kazuki Sato, Mika Reinisalo, Heidi Kidron, Masanori Tachikawa, Michitoshi Watanabe, Yasuo Uchida, Arto Urtti, Tetsuya Terasaki
The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier between neural retina and choroid. The RPE has several important vision supporting functions, such as transport mechanisms that may also modify pharmacokinetics in the posterior eye segment. Expression of plasma membrane transporters in the RPE cells has not been quantitated. The aim of this study was to characterize and compare transporter protein expression in the ARPE19 cell line and hfRPE (human fetal RPE) cells by using quantitative targeted absolute proteomics (QTAP)...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28112423/comparison-of-salivary-cortisol-and-%C3%AE-amylase-levels-and-psychological-profiles-in-patients-with-burning-mouth-syndrome
#10
Tahereh Nosratzehi, Saeedeh Salimi, Azadeh Parvaee
PURPOSE: The aim of the study was to compare salivary cortisol and α-amylase levels and psychological profiles in patients with burning mouth syndrome (BMS) and healthy subjects. METHODS AND MATERIALS: Spitting method was used to collect unstimulated salivary. Salivary cortisol and α-amylase levels were determined using ELISA and the Caraway starch-iodine technique. SLC-90 questionnaire was used to determine the psychological profiles. RESULTS: The difference between mean of salivary cortisol levels in patients with BMS and in healthy subjects was not significant (4...
January 23, 2017: Special Care in Dentistry
https://www.readbyqxmd.com/read/28099443/inhibition-of-human-drug-transporter-activities-by-the-pyrethroid-pesticides-allethrin-and-tetramethrin
#11
Lisa Chedik, Arnaud Bruyere, Marc Le Vee, Bruno Stieger, Claire Denizot, Yannick Parmentier, Sophie Potin, Olivier Fardel
Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulatory effects of these pesticides towards activities of main ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, using transporter-overexpressing cells...
2017: PloS One
https://www.readbyqxmd.com/read/28093031/the-inhibitory-effects-of-five-alkaloids-on-the-substrate-transport-mediated-through-human-organic-anion-and-cation-transporters
#12
Tahiatul Shams, Xiaoxi Lu, Ling Zhu, Fanfan Zhou
1. Human solute carrier transporters (SLCs) are important membrane proteins mediate the cellular transport of many endogenous and exogenous substances. Organic anion/cation transporters (OATs/OCTs) and organic anion transporting polypeptides (OATPs) are essential SLCs involved in drug influx. Drug-drug/herb interactions through competing for specific SLCs often lead to unsatisfied therapeutic outcomes and/or unwanted side effects. In this study, we comprehensively investigated the inhibitory effects of five clinically relevant alkaloids (dendrobine, matrine, oxymatrine, tryptanthrin and chelerythrine) on the substrate transport through several OATs/OCTs and OATPs...
February 1, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28091567/quantifying-the-relative-contributions-of-different-solute-carriers-to-aggregate-substrate-transport
#13
Mehdi Taslimifar, Lalita Oparija, Francois Verrey, Vartan Kurtcuoglu, Ufuk Olgac, Victoria Makrides
Determining the contributions of different transporter species to overall cellular transport is fundamental for understanding the physiological regulation of solutes. We calculated the relative activities of Solute Carrier (SLC) transporters using the Michaelis-Menten equation and global fitting to estimate the normalized maximum transport rate for each transporter (Vmax). Data input were the normalized measured uptake of the essential neutral amino acid (AA) L-leucine (Leu) from concentration-dependence assays performed using Xenopus laevis oocytes...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090714/transplantation-of-cd51-stem-leydig-cells-a-new-strategy-for-the-treatment-of-testosterone-deficiency
#14
Zhi Jun Zang, Jiancheng Wang, Zhihong Chen, Yan Zhang, Yong Gao, Zhijian Su, Ying Tuo, Yan Liao, Min Zhang, Qunfang Yuan, Chunhua Deng, Mei Hua Jiang, Andy Peng Xiang
Stem Leydig cell (SLC) transplantation could provide a new strategy for treating the testosterone deficiency. Our previous study demonstrated that CD51 (also called integrin αv) might be a putative cell surface marker for SLCs, but the physiological function and efficacy of CD51(+) SLCs treatment remain unclear. Here, we explore the potential therapeutic benefits of CD51(+) SLCs transplantation and whether these transplanted cells can be regulated by the hypothalamic-pituitary-gonadal (HPG) axis. CD51(+) cells were isolated from the testes of 12-weeks-old C57BL/6 mice, and we showed that such cells expressed SLC markers and that they were capable of self-renewal, extensive proliferation, and differentiation into multiple mesenchymal cell lineages and LCs in vitro...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28062543/multiple-slc-and-abc-transporters-contribute-to-the-placental-transfer-of-entecavir
#15
Zhiyuan Ma, Xi Yang, Ting Jiang, Mengru Bai, Caihong Zheng, Su Zeng, Dongli Sun, Huidi Jiang
Entecavir (ETV), a nucleoside analogue with high efficacy against hepatitis B virus, is recommended as a first-line antiviral drug for the treatment of chronic hepatitis B. However, scant information is available on the use of ETV in pregnancy. To better understand the safety of ETV in pregnant women, we aimed to demonstrate whether ETV could permeate placental barrier and the underlying mechanism. Our study showed that small amount of ETV could permeate across placenta in mice. ETV accumulation in activated or non-activated BeWo cells (treated with or without forskolin) was sharply reduced in the presence of 100 μM of adenosine, cytidine and in Na+ free medium, indicating that nucleoside transporters possibly mediate the uptake of ETV...
January 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28057955/summaries-of-safety-labeling-changes-approved-by-the-fda-boxed-warnings-highlights-july-september-2016
#16
Teresa Rubio
The FDA's MedWatch program safety labeling changes for boxed warnings are compiled quarterly for drugs and therapeutic biologics where important changes have been made to the safety information. Search of Drug Safety Labeling Changes (SLC) database was conducted on October 10, 2016 for date range "7/1/2016-9/30/2016", labeling section "Boxed Warning". These and other label changes are searchable in the Drug Safety Labeling Changes (SLC) database, where data are available to the public in downloadable and searchable formats...
December 2016: Hospital Pharmacy
https://www.readbyqxmd.com/read/28048675/tu-fg-209-07-medical-physics-1-0-versus-medical-physics-2-0-a-case-study
#17
D Carver, C Willis, P Stauduhar, T Nishino, J Wells, E Samei
PURPOSE: To illustrate how performance analytics can identify performance decrement in digital radiography systems. METHODS: Subsequent to a radiologist's image quality complaint, four different advanced methods contributed to root cause analysis. Our system was a GE Revolution XQi digital radiography unit. Initially, we reviewed weekly GE Quality Assurance Procedures (QAP) results in a database dating from 2001. Next, we evaluated objective image quality metrics of individual PA Chest radiographs acquired...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28041944/large-scale-identification-of-differentially-expressed-genes-during-pupa-development-reveals-solute-carrier-gene-is-essential-for-pupal-pigmentation-in-chilo-suppressalis
#18
Yang Sun, Shuijin Huang, Shuping Wang, Dianhao Guo, Chang Ge, Huamei Xiao, Wencai Jie, Qiupu Yang, Xiaolu Teng, Fei Li
Insects undergo metamorphosis, involving an abrupt change in body structure through cell growth and differentiation. Rice stem stripped borer (SSB), Chilo suppressalis, is one of the most destructive rice pests. However, little is known about the regulation mechanism of metamorphosis development in this notorious insect pest. Here, we studied the expression of 22,197 SSB genes at seven time points during pupa development with a customized microarray, identifying 622 differentially expressed genes (DEG) during pupa development...
December 29, 2016: Journal of Insect Physiology
https://www.readbyqxmd.com/read/28025785/significance-of-oct1-expression-in-acute-myeloid-leukemia
#19
Ewa Stefanko, Justyna Rybka, Bożena Jaźwiec, Olga Haus, Sylwia Stąpor, Kazimierz Kuliczkowski, Tomasz Wróbel
Organic cation transporter 1 (OCT1) is one of the membrane proteins in the large solute carrier (SLC) family. It participates in the transport of organic cations, i.e. nutrients, neurotransmitters, metabolites or drugs in an electrogenic manner and translocate various cationic cytostatics. Knowledge concerning the expression of drug transporters in tumor cells may help to develop cytotoxic agents that are targeted to specific tumors. OCT1 expression and its relationship to the proliferation of cancer cells, development of metastases and resistance to chemotherapy has been observed in solid tumors...
December 26, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28001028/preparation-of-a-thermally-light-transmittance-controllable-film-from-a-coexistent-system-of-polymer-dispersed-and-polymer-stabilized-liquid-crystals
#20
Shu-Meng Guo, Xiao Liang, Cui-Hong Zhang, Mei Chen, Chen Shen, Lan-Ying Zhang, Xiao Yuan, Bao-Feng He, Huai Yang
Polymer-dispersed liquid crystal (PDLC) and polymer-stabilized liquid crystal (PSLC) systems are the two primary distinct systems in the field of liquid crystal (LC) technology, and they are differentiated by their unique microstructures. Here, we present a novel coexistent system of polymer-dispersed and polymer-stabilized liquid crystals (PD&SLCs), which forms a homeotropically aligned polymer network (HAPN) within the LC droplets after a microphase separation between the LC and polymer matrix and combines the advantages of both the PDLC and PSLC systems...
January 11, 2017: ACS Applied Materials & Interfaces
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