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Essraa M Al-Essawe, Margareta Wallgren, Manuela Wulf, Christine Aurich, Beatriz Macías-García, Ylva Sjunnesson, Jane M Morrell
Seminal plasma (SP) contains proteins that may influence cryosurvival and prevent capacitation-like changes due to freezing and thawing. The objective of this study was to investigate the effect of adding pooled SP from "good" (GF) or "bad" (BF) freezer stallions on sperm cells' fertilizing ability. "Good freezers" refers to stallions that usually produce ejaculates which can withstand cryopreservation, whilst "bad freezer" stallions produce ejaculates which cannot tolerate the freezing process...
April 26, 2018: Theriogenology
Emelie Perland, Sofie V Hellsten, Nadine Schweizer, Vasiliki Arapi, Fatemah Rezayee, Mona Bushra, Robert Fredriksson
[This corrects the article DOI: 10.1371/journal.pone.0186325.].
2018: PloS One
Jeremiah D Momper, Sanjay K Nigam
The ontogeny of drug transport and metabolism is generally studied independently in tissues, yet in the immediate postnatal period the developmental regulation of transporters and metabolizing enzymes must be coordinated. Using the Remote Sensing and Signaling Hypothesis as a framework, we describe how a systems physiology view helps to make sense of how inter-organ communication via hepatic, renal, and intestinal transporters and drug metabolizing (DMEs) enzymes is regulated from the immediate postnatal period through adulthood...
May 10, 2018: Expert Opinion on Drug Metabolism & Toxicology
Juan Chen, Qi-Biao Su, Yu-Qian Tao, Jia-Ming Qin, Yi Zhou, Shan Zhou, Hong-Liang Li, Zhuo-Jia Chen, Ya-Fang Zhou, Lie-Min Zhou, Xue-Ding Wang, Min Huang
Valproic acid (VPA), a widely used antiepileptic drug, is characterized by intensive inter-individual variability in concentration. Both efflux and influx transporters are reported to play important roles in the disposition of VPA, however, no comprehensive investigation into the association of the single nucleotide polymorphism (SNP) in ABC/SLC families with VPA concentration are reported. In the present study, we investigated the association of 12 SNPs in ABCC2, ABCC4, ABCG2, MCT1, MCT2, and OATP2B1 in 187 Chinese patients with epilepsy on VPA monotherapy with the trough concentrations of VPA...
May 1, 2018: Die Pharmazie
Weibin Zha
The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions...
April 2018: Journal of Food and Drug Analysis
Markus Grube, Paul Hagen, Gabriele Jedlitschky
Neurosteroids, comprising pregnane, androstane, and sulfated steroids can alter neuronal excitability through interaction with ligand-gated ion channels and other receptors and have therefore a therapeutic potential in several brain disorders. They can be formed in brain cells or are synthesized by an endocrine gland and reach the brain by penetrating the blood-brain barrier (BBB). Especially sulfated steroids such as pregnenolone sulfate (PregS) and dehydroepiandrosterone sulfate (DHEAS) depend on transporter proteins to cross membranes...
2018: Frontiers in Pharmacology
Hajar Al Feteisi, Zubida M Al-Majdoub, Brahim Achour, Narciso Couto, Amin Rostami-Hodjegan, Jill Barber
The blood-brain barrier (BBB) maintains brain homeostasis by tightly regulating the exchange of molecules with systemic circulation. It consists primarily of microvascular endothelial cells surrounded by astrocytic endfeet, pericytes, and microglia. Understanding the make-up of transporters in rat BBB is essential to the translation of pharmacological and toxicological observations into humans. In this study, experimental workflows are presented in which the optimization of (a) isolation of rat brain microvessels, (b) enrichment of endothelial cells, and (c) extraction and digestion of proteins were evaluated, followed by identification and quantification of BBB proteins...
April 20, 2018: Journal of Neurochemistry
Pascale Fisel, Elke Schaeffeler, Matthias Schwab
The solute carrier (SLC) SLC16 gene family comprises 14 members and encodes for monocarboxylate transporters (MCTs), which mediate the absorption and distribution of monocarboxylic compounds across plasma membranes. As the knowledge about their physiological function, activity, and regulation increases, their involvement and contribution to cancer and other diseases become increasingly evident. Moreover, promising opportunities for therapeutic interventions by directly targeting their endogenous functions or by exploiting their ability to deliver drugs to specific organ sites emerge...
April 16, 2018: Clinical and Translational Science
E N Knyazev, D V Mal'tseva, A A Zacharyants, G S Zakharova, O V Zhidkova, A A Poloznikov
Endothelial HUVEC cells used as an in vitro model of the endothelial monolayer in placental barrier were activated by TNFα in a dose of 2 ng/ml for 24 h. Significant changes in the expression of genes of the SLC family transport protein were observed: an increase in the expression of SLC7A2, SLC12A2, SLC9B2, SLC25A37, SLC16A9, and SLC41A2 and a decrease in the expression of SLC40A1. These transporters participate in the transport of iron, magnesium, sodium, potassium, and chloride ions, protons, and amino acids...
April 16, 2018: Bulletin of Experimental Biology and Medicine
E Varela, J Rey, E Plaza, P Muñoz de Propios, J M Ortiz-Rodríguez, M Álvarez, L Anel-López, L Anel, P De Paz, M C Gil, J M Morrell, C Ortega-Ferrusola
Contaminating bacteria present in stallion ejaculates may compromise sperm quality during storage. Different procedures have been used to reduce the load of microorganisms in semen and avoid bacterial growth during storage. The aims of this study were: 1) to evaluate different techniques to eliminate bacteria in semen 2) to study the relationship between total microflora load (TML) and ROS production; and 3) to determine if TML affects the functionality of cool-stored sperm. Ejaculates from 11 stallions were split and processed in 3 ways: A...
March 26, 2018: Theriogenology
Xiaoyun Bai, Trevor F Moraes, Reinhart A F Reithmeier
The human solute carriers (SLCs) comprise over 400 different transporters, organized into 65 families ( ) based on their sequence homology and transport function. SLCs are responsible for transporting extraordinarily diverse solutes across biological membranes, including inorganic ions, amino acids, lipids, sugars, neurotransmitters and drugs. Most of these membrane proteins function as coupled symporters (co-transporters) utilizing downhill ion (H+ or Na+ ) gradients as the driving force for the transport of substrate against its concentration gradient into cells...
April 13, 2018: Molecular Membrane Biology
Thanapol Nongbua, Essraa M Al-Essawe, Anders Edman, Anders Johannisson, Jane M Morrell
Variations in fertility between bulls with comparable sperm quality could be due to differences in their seminal plasma (SP). The aim of this study was to investigate the effect of adding bovine SP from bulls of known fertility to SP-free sperm samples. After removal of SP by Single Layer Centrifugation, resuspended sperm pellets were treated with SP from high or low fertility bulls at 0% (control), 1%, or 5% before freezing. Sperm quality was evaluated after thawing. Data were analyzed using Proc MIXED, SAS®...
April 5, 2018: Systems Biology in Reproductive Medicine
Ji-Eun Kim, Jaesung Choi, JooYong Park, Chulbum Park, Se Mi Lee, Seong Eun Park, Nan Song, Seokang Chung, Hyuna Sung, Wonshik Han, Jong Won Lee, Sue K Park, Mi Kyung Kim, Dong-Young Noh, Keun-Young Yoo, Daehee Kang, Ji-Yeob Choi
Membrane transporters can be major determinants of the pharmacokinetic profiles of anticancer drugs. The associations between genetic variations of ATP-binding cassette (ABC) and solute carrier (SLC) genes and cancer survival were investigated through a meta-analysis and an association study in the Seoul Breast Cancer Study (SEBCS). Including the SEBCS, the meta-analysis was conducted among 38 studies of genetic variations of transporters on various cancer survivors. The population of SEBCS consisted of 1338 breast cancer patients who had been treated with adjuvant chemotherapy...
April 4, 2018: Pharmacogenomics Journal
Erkan Yilmaz, Halil İbrahim Ulusoy, Özge Demir, Mustafa Soylak
A sensitive analytical methodology was investigated to concentrate and determine of sildenafil citrate (SLC) present at trace level in herbal supplementary products. The proposed method is based on simple and sensitive pre-concentration of SLC by using magnetic solid phase extraction with new developed magnetic nanodiamond/graphene oxide hybrid (Fe3 O4 @ND@GO) material as a sorbent. Experimental variables affecting the extraction efficiency of SLC like; pH, sample volume, eluent type and volume, extraction time and amount of adsorbent were studied and optimized in detail...
March 15, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Mousumi Majumder, Pinki Nandi, Ahmed Omar, Kingsley Chukwunonso Ugwuagbo, Peeyush K Lala
G-protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G-protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions, as well as in the pathology of many diseases, including cancer progression and metastasis...
March 29, 2018: International Journal of Molecular Sciences
Mehdi Taslimifar, Stefano Buoso, Francois Verrey, Vartan Kurtcuoglu
The homeostatic regulation of large neutral amino acid (LNAA) concentration in the brain interstitial fluid (ISF) is essential for proper brain function. LNAA passage into the brain is primarily mediated by the complex and dynamic interactions between various solute carrier (SLC) transporters expressed in the neurovascular unit (NVU), among which SLC7A5/LAT1 is considered to be the major contributor in microvascular brain endothelial cells (MBEC). The LAT1-mediated trans-endothelial transport of LNAAs, however, could not be characterized precisely by available in vitro and in vivo standard methods so far...
2018: Frontiers in Physiology
Benjamin Clémençon, Benjamin P Lüscher, Matthias A Hediger
INTRODUCTION: Membrane proteins represent roughly one third of the human proteome and many of them serve as targets of therapeutic drugs. An exception is the SLC solute carrier superfamily with only a handful of approved drugs targeting SLCs. Indeed, for many of the SLCs, the natural transport substrates are still unknown. A major limitation for SLCs has been the difficulty to thoroughly characterize these multimembrane spanning proteins. The intrinsic properties of membrane proteins with alternative hydrophobic and hydrophilic domains lead to instability, making the purification tasks even more challenging compared to soluble proteins...
March 23, 2018: Journal of Pharmacological and Toxicological Methods
Jane Falconer, Anne N Murphy, Stephen Young, Andrew R Clark, Stefano Tiziani, Monica Guma, Christopher D Buckley
Metabolomic studies of body fluids show that immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) are associated with metabolic disruption. This is likely to reflect the increased bioenergetic and biosynthetic demands of sustained inflammation and changes to nutrient and oxygen availability in damaged tissue. The synovial membrane lining layer is the principle site of inflammation in RA. Here the resident cells are the fibroblast-like synoviocytes (FLS) and the synovial tissue macrophages (STM), which are transformed toward overproduction of enzymes which degrade cartilage and bone, and cytokines which promote immune cell infiltration...
March 26, 2018: Arthritis & Rheumatology
Benjamin G Janesko, Emil Proynov, Giovanni Scalmani, Michael J Frisch
Rung 3.5 functionals are a new class of approximations for density functional theory. They provide a flexible intermediate between exact (Hartree-Fock, HF) exchange and semilocal approximations for exchange. Existing Rung 3.5 functionals inherit semilocal functionals' limitations in atomic cores and density tails. Here we address those limitations using range-separated admixture of HF exchange. We present three new functionals. LRC-ωΠLDA combines long-range HF exchange with short-range Rung 3.5 ΠLDA exchange...
March 14, 2018: Journal of Chemical Physics
Clara Malo, Elizabeth G Crichton, Jane M Morrell, Budhan S Pukazhenthi, Anders Johannisson, Rebecca Splan, Julian A Skidmore
Colloids have been successfully used in a number of species to improve sperm populations for IVF and for cryopreservation The usefulness of Single Layer Centrifugation (SLC) for freezing dromedary camel spermatozoa in two different extenders was evaluated by examining the motility, viability, acrosome status, DNA integrity, and ability of cryopreserved sperm to penetrate oocytes in vitro in a heterologus IVF system. Two ejaculates from each of five males were divided into four aliquots: two were processed by SLC (selected) while two were centrifuged without colloid (control)...
May 2018: Animal Reproduction Science
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