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https://www.readbyqxmd.com/read/29331752/synthesis-of-gold-i-phosphine-complexes-containing-the-2-brc6f4pph2-ligand-evaluation-of-anticancer-activity-in-2d-and-3d-spheroidal-models-of-hela-cancer-cells
#1
T Srinivasa Reddy, Steven H Privér, Nedaossadat Mirzadeh, Suresh K Bhargava
Newly synthesised mononuclear gold complexes containing the 2-BrC6F4PPh2 ligand have been fully characterised and their anticancer activity towards five human tumor [prostate (PC3), glioblastoma (U87MG), cervical (HeLa), fibrosarcoma (HT1080), ovarian (SKOV-3)] and normal human embryonic kidney (Hek-293T) cell lines investigated. Some of the synthesised gold complexes displayed higher cytotoxicity than cisplatin towards PC-3, HeLa and U87MG cells and inhibited the thioredoxin reductase (TrxR) enzyme, which is considered a potential target for new compounds in cancer treatment...
December 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29329779/receptor-and-cellular-compartment-specific-activation-of-the-camp-pka-pathway-by-%C3%AE-1-adrenergic-and-eta-endothelin-receptors
#2
Ryan D Martin, Yalin Sun, Kyla Bourque, Nicolas Audet, Asuka Inoue, Jason C Tanny, Terence E Hébert
The signaling functions of many G protein-coupled receptors (GPCRs) expressed in the myocardium are incompletely understood. Among these are the endothelin receptor (ETR) family and α1-adrenergic receptor (α1-AR), which are thought to couple to the G protein Gαq. In this study, we used transcriptome analysis to compare the signaling networks downstream of these receptors in primary neonatal rat cardiomyocytes. This analysis indicated increased expression of target genes of cAMP responsive element modulator (CREM) after 24 h treatment with the α1-AR agonist phenylephrine, but not the ETR agonist endothelin-1, suggesting a specific role for the α1-AR in promoting cAMP production in cardiomyocytes...
January 9, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29325755/amphotericin-b-albumin-conjugates-synthesis-toxicity-and-anti-fungal-activity
#3
Sneha Gurudevan, Arul Prakash Francis, A Jayakrishnan
Amphotericin B (AmB), a hydrophobic drug with negligible aqueous solubility was conjugated to bovine serum albumin (BSA) via amide bond coupling to give 6 to 8 wt% drug payload. The resulting conjugate was characterized using SDS-PAGE and UV-visible, FTIR and CD spectroscopy. The conjugate was water-soluble to the extent of 150 mg/ml, was non-toxic to HEK 293 T cells at a concentration of 500 μg/ml (equivalent to ~30 μg AmB) and showed hemolysis of <5% at 200 μg/ml (equivalent to ~12 μg AmB) against human erythrocytes in vitro...
January 8, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29317801/is-there-a-conflict-between-general-practitioners-applying-guidelines-for-antibiotic-prescribing-and-including-their-patients-preferences
#4
Anne Em Brabers, Thamar Em Van Esch, Peter P Groenewegen, Karin Hek, Pé Mullenders, Liset Van Dijk, Judith D De Jong
Objectives: One perceived barrier to guideline adherence is the existence of conflicting patient preferences. We examined whether patient preferences influence the prescription of antibiotics in general practice, and how this affects guideline adherence. We hypothesized that preferences play a larger role in prescribing antibiotics if the guideline allows for preferences to be taken into account, ie, if prescribing antibiotics is an option which can be considered rather than a clear recommendation to prescribe or not...
2018: Patient Preference and Adherence
https://www.readbyqxmd.com/read/29317724/rfx1-and-rfx3-transcription-factors-interact-with-the-d-sequence-of-adeno-associated-virus-inverted-terminal-repeat-and-regulate-aav-transduction
#5
Laura Julien, Julie Chassagne, Cécile Peccate, Stéphanie Lorain, France Piétri-Rouxel, Olivier Danos, Sofia Benkhelifa-Ziyyat
Adeno-associated virus (AAV) transduction efficiency depends on the way in which cellular proteins process viral genomes in the nucleus. In this study, we have investigated the binding of nuclear proteins to the double stranded D (dsD) sequence of the AAV inverted terminal repeat (ITRs) by electromobility shift assay. We present here several lines of evidence that transcription factors belonging to the RFX protein family bind specifically and selectively to AAV2 and AAV1 dsD sequences. Using supershift experiments, we characterize complexes containing RFX1 homodimers and RFX1/RFX3 heterodimers...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29315258/methods-for-using-small-non-coding-rnas-to-improve-recombinant-protein-expression-in-mammalian-cells
#6
REVIEW
Sarah Inwood, Michael J Betenbaugh, Joseph Shiloach
The ability to produce recombinant proteins by utilizing different "cell factories" revolutionized the biotherapeutic and pharmaceutical industry. Chinese hamster ovary (CHO) cells are the dominant industrial producer, especially for antibodies. Human embryonic kidney cells (HEK), while not being as widely used as CHO cells, are used where CHO cells are unable to meet the needs for expression, such as growth factors. Therefore, improving recombinant protein expression from mammalian cells is a priority, and continuing effort is being devoted to this topic...
January 9, 2018: Genes
https://www.readbyqxmd.com/read/29313060/an-md2-derived-peptide-promotes-lps-aggregation-facilitates-its-internalization-in-thp-1-cells-and-inhibits-lps-induced-pro-inflammatory-responses
#7
Anshika Tandon, Munesh Kumar Harioudh, Nayab Ishrat, Amit Kumar Tripathi, Saurabh Srivastava, Jimut Kanti Ghosh
MD2, a 160-residue accessory glycoprotein, is responsible for the recognition and binding of Gram-negative bacterial membrane component, lipopolysaccharide (LPS). Internalization of pathogen inside the mononuclear phagocytes has also been attributed to MD2 which leads to the clearance of pathogens from the host. However, not much is known about the segments in MD2 that are responsible for LPS interaction or internalization of pathogen inside the defense cells. A 16-residue stretch (MD54) from MD2 protein has been identified that possesses a short heptad repeat sequence and four cationic residues enabling it to participate in both hydrophobic and electrostatic interactions with LPS...
January 8, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29311258/molecular-mechanisms-of-cutis-laxa-and-distal-renal-tubular-acidosis-causing-mutations-in-v-atpase-a-subunits-atp6v0a2-and-atp6v0a4
#8
Sally Esmail, Norbert Kartner, Yeqi Yao, Joo Wan Kim, Reinhart A F Reithmeier, Morris F Manolson
The a subunit is the largest of 15 different subunits that make up the vacuolar H+-ATPase (V-ATPase) complex, where it functions in proton translocation. In mammals, this subunit has four paralogous isoforms, a1-a4, which may encode signals for targeting assembled V-ATPases to specific intracellular locations. Despite the functional importance of the a subunit, its structure remains controversial. By studying molecular mechanisms of human disease-causing missense mutations within a subunit isoforms, we may identify domains critical for V-ATPase targeting, activity and/or regulation...
January 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29311110/long-lasting-in-vivo-effects-of-the-cannabinoid-cb1-antagonist-am6538
#9
Carol A Paronis, Girish R Chopda, Kiran Vemuri, Ani S Zakarian, Alexandros Makriyannis, Jack Bergman
AM6538 is a cannabinoid antagonist that binds CB1 receptors expressed in HEK-293 cells in a wash-resistant manner. The effects of AM6538 in live animals has not previously been established. We characterized the antagonist effects of AM6538 in male mice, using a warm-water tail-withdrawal assay, and in male squirrel monkeys trained to discriminate the CB1 agonist AM4054 from vehicle. The cannabinoid agonists WIN 55,212, Δ9-tetrahydrocannabinol (THC), and AM4054 all produced 100% maximum possible antinociceptive effects in mice following vehicle pretreatment...
January 8, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29306762/microfluidic-platform-for-single-cell-analysis-under-dynamic-spatial-and-temporal-stimulation
#10
Jiyoung Song, Hyunryul Ryu, Minhwan Chung, Youngtaek Kim, Yannick Blum, Sung Sik Lee, Olivier Pertz, Noo Li Jeon
Recent research on cellular responses is shifting from static observations recorded under static stimuli to real-time monitoring in a dynamic environment. Since cells sense and interact with their surrounding microenvironment, an experimental platform where dynamically changing cellular microenvironments should be recreated in vitro. There has been a lack of microfluidic devices to support spatial and temporal stimulations in a simple and robust manner. Here, we describe a microfluidic device that generates dynamic chemical gradients and pulses in both space and time using a single device...
December 27, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29302757/indinavir-alters-the-pharmacokinetics-of-lamivudine-partially-via-inhibition-of-multidrug-and-toxin-extrusion-protein-1-mate1
#11
Qing Li, Zhi Ye, Peng Zhu, Dong Guo, Hong Yang, Jin Huang, Wei Zhang, James E Polli, Yan Shu
PURPOSE: Lamivudine, a characterized substrate for human multidrug and toxin extrusion protein 1 (hMATE1) in vitro, was commonly used with indinavir as a therapy against human immunodeficiency virus (HIV). We aimed to investigate whether mouse MATE1 is involved in the disposition of lamivudine in vivo, and whether there is any transporter-mediated interaction between indinavir and lamivudine. METHODS: The role of MATE1 in the disposition of lamivudine was determined using Mate1 wild type (+/+) and knockout (-/-) mice...
January 4, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29290262/gcc2-alk-as-a-targetable-fusion-in-lung-adenocarcinoma-and-its-enduring-clinical-responses-to-alk-inhibitors
#12
Junhong Jiang, Xue Wu, Xiaoling Tong, Wangzhi Wei, Anan Chen, Xiaonan Wang, Yang W Shao, Jianan Huang
OBJECTIVES: ALK, RET and ROS1 fusions have been identified as treatable targets in 5%-15% of non-small-cell lung cancers, and thanks to the advanced sequencing technologies, their new partner genes have been steadily detected. Here we identified a rare fusion of ALK (GCC2-ALK) in a patient with advanced lung adenocarcinoma and monitored the treatment efficacy of ALK inhibitors on this patient. We further performed in vitro functional studies of this fusion protein for evaluating its oncogenic potential...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29286484/a-protocol-for-the-production-of-integrase-deficient-lentiviral-vectors-for-crispr-cas9-mediated-gene-knockout-in-dividing-cells
#13
Sriram Vijayraghavan, Boris Kantor
Lentiviral vectors are an ideal choice for delivering gene-editing components to cells due to their capacity for stably transducing a broad range of cells and mediating high levels of gene expression. However, their ability to integrate into the host cell genome enhances the risk of insertional mutagenicity and thus raises safety concerns and limits their usage in clinical settings. Further, the persistent expression of gene-editing components delivered by these integration-competent lentiviral vectors (ICLVs) increases the probability of promiscuous gene targeting...
December 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29280428/african-and-asian-zika-virus-isolates-display-phenotypic-differences-both-in-vitro-and-in-vivo
#14
Darci R Smith, Thomas R Sprague, Bradley S Hollidge, Stephanie M Valdez, Susana L Padilla, Stephanie A Bellanca, Joseph W Golden, Susan R Coyne, David A Kulesh, Lynn Jean Miller, Andrew D Haddow, Jeff W Koehler, Gregory D Gromowski, Richard G Jarman, Maria Theresa P Alera, In-Kyu Yoon, Rome Buathong, Robert G Lowen, Christopher D Kane, Timothy D Minogue, Sina Bavari, Robert B Tesh, Scott C Weaver, Kenneth J Linthicum, Margaret L Pitt, Farooq Nasar
Zika virus (ZIKV) is a mosquito-borne member of the genus Flavivirus that has emerged since 2007 to cause outbreaks in Africa, Asia, Oceania, and most recently, in the Americas. Here, we used an isolate history as well as genetic and phylogenetic analyses to characterize three low-passage isolates representing African (ArD 41525) and Asian (CPC-0740, SV0127-14) lineages to investigate the potential phenotypic differences in vitro and in vivo. The African isolate displayed a large plaque phenotype (∼3-4 mm) on Vero and HEK-293 cells, whereas the Asian isolates either exhibited a small plaque phenotype (∼1-2 mm) or did not produce any plaques...
December 26, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29278317/transferrin-copper-nanocluster-doxorubicin-nanoparticles-as-targeted-theranostic-cancer-nanodrug
#15
Upashi Goswami, Anushree Dutta, Asif Raza, Raghuram Kandimalla, Sanjeeb Kalita, Siddhartha Sankar Ghosh, Arun Chattopadhyay
Transferrin (Tf) templated luminescent blue copper nanoclusters (Tf-CuNCs) are synthesized. They are further formulated into spherical transferrin copper nanocluster-doxorubicin nanoparticles (Tf-CuNC-Dox-NPs) based on electrostatic interaction with doxorubicin (Dox). The as synthesized Tf-CuNC-Dox-NPs are explored for bioimaging and targeted drug delivery to delineate high therapeutic efficacy. Förster resonance energy transfer (FRET) within the Tf-CuNC-Dox-NPs exhibited striking red luminescence, wherein the blue luminescence of Tf-CuNCs (donor) is quenched due to absorption by Dox (acceptor)...
December 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29277707/the-in-vitro-metabolism-of-11%C3%AE-hydroxyprogesterone-and-11-ketoprogesterone-to-11-ketodihydrotestosterone-in-the-backdoor-pathway
#16
Desmaré van Rooyen, Rachelle Gent, Lise Barnard, Amanda C Swart
Increased circulating 11β-hydroxyprogesterone (11OHP4), biosynthesised in the human adrenal, is associated with 21-hydroxylase deficiency in congenital adrenal hyperplasia. 17α-hydroxyprogesterone levels are also increased, with the steroid's metabolism to dihydrotestosterone in the backdoor pathway contributing to hyperandrogenic clinical conditions. In this study we investigated the in vitro biosynthesis and downstream metabolism of 11OHP4. Both cytochrome P450 11β-hydroxylase and aldosterone synthase catalyse the biosynthesis of 11OHP4 from progesterone (P4) which is converted to 11-ketoprogesterone (11KP4) by 11β-hydroxysteroid dehydrogenase type 2, while type 1 readily catalysed the reverse reaction...
December 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29277637/synthesis-and-characterisation-of-arsenic-nanoparticles-and-its-interaction-with-dna-and-cytotoxic-potential-on-breast-cancer-cells
#17
A Subastri, V Arun, Preeti Sharma, E Preedia Babu, A Suyavaran, S Nithyananthan, Ghedeir M Alshammari, B Aristatile, V Dharuman, C Thirunavukkarasu
Therapeutic applications of arsenic trioxide (ATO) are limited due to their severe adverse effects. However, nanoparticles of ATO might possess inimitable biologic effects based on their structure and size which differ from their parent molecules. Based on this conception, AsNPs were synthesized from ATO and comparatively analysed for their interaction mechanism with DNA using spectroscopic & electrochemical techniques. Finally, anti-proliferative activity was assessed against different breast cancer cells (MDA-MB-231 & MCF-7) and normal non-cancerous cells (HEK-293)...
December 22, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29277457/development-of-fluorescence-imaging-probes-for-nicotinic-acetylcholine-%C3%AE-4%C3%AE-2%C3%A2-receptors
#18
Gurleen K Samra, Irakli Intskirveli, Anitha P Govind, Christopher Liang, Ronit Lazar, William N Green, Raju Metherate, Jogeshwar Mukherjee
Nicotinic acetylcholine α4β2∗ receptors (nAChRs) are implicated in various neurodegenerative diseases and smoking addiction. Imaging of brain high-affinity α4β2∗ nAChRs at the cellular and subcellular levels would greatly enhance our understanding of their functional role. Since better resolution could be achieved with fluorescent probes, using our previously developed positron emission tomography (PET) imaging agent [18F]nifrolidine, we report here design, synthesis and evaluation of two fluorescent probes, nifrodansyl and nifrofam for imaging α4β2∗ nAChRs...
December 17, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29276473/ferric-chelate-reductase-1-like-protein-frrs1l-associates-with-dynein-vesicles-and-regulates-glutamatergic-synaptic-transmission
#19
Wenyan Han, Huiqing Wang, Jun Li, Shizhong Zhang, Wei Lu
In the brain, AMPA receptors (AMPARs)-mediated excitatory synaptic transmission is critically regulated by the receptor auxiliary subunits. Recent proteomic studies have identified that Ferric Chelate Reductase 1 Like protein (FRRS1L), whose mutations in human lead to epilepsy, choreoathetosis, and cognitive deficits, is present in native AMPAR complexes in the brain. Here we have characterized FRRS1L in both heterologous cells and in mouse neurons. We found that FRRS1L interacts with both GluA1 and GluA2 subunits of AMPARs, but does not form dimers/oligomers, in HEK cells...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29274875/the-multimodal-antidepressant-vortioxetine-may-facilitate-pyramidal-cell-firing-by-inhibition-of-5-ht3-receptor-expressing-interneurons-an-in-vitro-study-in-rat-hippocampus-slices
#20
Elena Dale, Morten Grunnet, Alan L Pehrson, Kristen Frederiksen, Peter H Larsen, Jacob Nielsen, Tine B Stensbøl, Bjarke Ebert, Haolan Yin, Dunguo Lu, Huiquing Liu, Thomas N Jensen, Charles R Yang, Connie Sanchez
The multimodal antidepressant vortioxetine is thought to mediate its pharmacological effects via 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, 5-HT1D, 5-HT3, 5-HT7 receptor antagonism and 5-HT transporter inhibition. Here we studied vortioxetine's functional effects across species (canine, mouse, rat, guinea pig and human) in cellular assays with heterologous expression of 5-HT3A receptors (in Xenopus oocytes and HEK-293 cells) and in mouse neuroblastoma N1E-115 cells with endogenous expression of 5-HT3A receptors...
December 21, 2017: Brain Research
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