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https://www.readbyqxmd.com/read/28530711/a-combinatorial-screen-of-the-cloud-uncovers-a-synergy-targeting-the-androgen-receptor
#1
Marco P Licciardello, Anna Ringler, Patrick Markt, Freya Klepsch, Charles-Hugues Lardeau, Sara Sdelci, Erika Schirghuber, André C Müller, Michael Caldera, Anja Wagner, Rebecca Herzog, Thomas Penz, Michael Schuster, Bernd Boidol, Gerhard Dürnberger, Yasin Folkvaljon, Pär Stattin, Vladimir Ivanov, Jacques Colinge, Christoph Bock, Klaus Kratochwill, Jörg Menche, Keiryn L Bennett, Stefan Kubicek
Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC)...
May 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28530706/akt-is-indispensable-for-coordinating-par-4-jnk-cross-talk-in-p21-downmodulation-during-er-stress
#2
R U Rasool, D Nayak, S Chakraborty, M M Faheem, B Rah, P Mahajan, V Gopinath, A Katoch, Z Iqra, S K Yousuf, D Mukherjee, L D Kumar, A Nargotra, A Goswami
The double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28529825/innovative-approaches-to-glaucoma-management-of-boston-keratoprosthesis-type-1
#3
Thasarat S Vajaranant, Jessica Liu, Jacob Wilensky, M Soledad Cortina, Ahmad A Aref
Glaucoma remains a prevalent disorder and visual limiting factor after Boston keratoprosthesis type 1 implantation. Patients with glaucoma have worse initial and late visual acuity outcomes after otherwise successful keratoprosthesis implantation. Management of glaucoma in the setting of a keratoprosthesis is challenging because of relatively rapid progression and an inability to accurately measure intraocular pressure (IOP). In addition, there are no standard guidelines for glaucoma surveillance and monitoring after keratoprosthesis surgery...
September 2016: Current Ophthalmology Reports
https://www.readbyqxmd.com/read/28529769/une-surstructure-de-%C3%AE-ge-type-diamant-induite-par-un-dopage-d-anti-moine
#4
Adrian Gómez Herrero, Lamia Hammoudi, Mohammed Kars, Thierry Roisnel, L Carlos Otero-Diáz
Single crystals of anti-mony-doped germanium, Ge1-x Sb x+0.01 (x ≃ 0.0625), were grown by chemical transport reaction. The alloy crystallizes as a superstructure of diamond-type α-Ge. All atoms in the asymmetric unit lie on special positions and are characterized by strong covalent bonds. The anti-mony atoms substitute for one germanium atom at full occupancy at Wyckoff position 4a (site symmetry -43m), and are also at an adjacent tetra-hedral inter-stitial site with partially occupation (16%) at position 4c (or 4d) (site symmetry -43m)...
May 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28528012/impact-of-total-pars-plana-vitrectomy-on-postoperative-complications-in-aphakic-snap-on-type-1-boston-keratoprosthesis
#5
Victor L Perez, Ella H Leung, Audina M Berrocal, Thomas A Albini, Jean Marie Parel, Guillermo Amescua, Eduardo C Alfonso, Tayyeba K Ali, Allister Gibbons
PURPOSE: To determine the impact of total pars plana vitrectomies (PPVs) with peripheral shaving of the vitreous base on the rates of postoperative complications in patients with aphakic, snap-on type I Boston keratoprostheses (KPros). DESIGN: Retrospective, consecutive case series. PARTICIPANTS: A total of 48 eyes in 46 patients with implantation of aphakic, snap-on type 1 Boston KPros performed at a tertiary care facility between January 1, 2007, and December 31, 2013, were included...
May 17, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28527958/treadmill-exercise-produces-neuroprotective-effects-in-a-murine-model-of-parkinson-s-disease-by-regulating-the-tlr2-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#6
Jung-Hoon Koo, Yong-Chul Jang, Dong-Ju Hwang, Hyun-Seob Um, Nam-Hee Lee, Jae-Hoon Jung, Joon-Yong Cho
Parkinson's disease (PD) is characterized by progressive dopamine depletion and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Treadmill exercise is a promising non-pharmacological approach for reducing the risk of PD and other neuroinflammatory disorders, such as Alzheimer's disease. The goal of this study was to investigate the effects of treadmill exercise on α-synuclein-induced neuroinflammation and neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28527614/n-o-344-salpingectomie-opportuniste-et-autres-m%C3%A3-thodes-pour-r%C3%A3-duire-le-risque-de-cancer-de-l-ovaire-de-la-trompe-de-fallope-et-du-p%C3%A3-ritoine-dans-la-population-g%C3%A3-n%C3%A3-rale
#7
Shannon Salvador, Stephanie Scott, Julie Ann Francis, Anita Agrawal, Christopher Giede
OBJECTIF: La présente directive clinique examine les avantages potentiels de la salpingectomie opportuniste pour prévenir le développement du cancer séreux de grade élevé de l'ovaire, de la trompe de Fallope et du péritoine à la lumière de données probantes actuelles selon lesquelles ce type de cancer prendrait naissance dans la trompe de Fallope. UTILISATEURS CIBLES: Gynécologues, obstétriciens, médecins de famille, infirmières autorisées, infirmières praticiennes, résidents et fournisseurs de soins de santé...
June 2017: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
https://www.readbyqxmd.com/read/28527031/choroidal-thickness-in-chronic-rhegmatogenous-retinal-detachment-before-and-after-surgery-and-comparison-with-acute-cases
#8
Isil Sayman Muslubas, Mumin Hocaoglu, Mehmet Giray Ersoz, Serra Arf, Murat Karacorlu
PURPOSE: To evaluate subfoveal choroidal thickness (SCT) in cases with chronic rhegmatogenous retinal detachment (RRD), before and after pars plana vitrectomy, and cases with acute RRD using optical coherence tomography. METHODS: This retrospective study included 24 eyes with chronic RRD and 26 eyes with recent-onset RRD. Best corrected visual acuity, intraocular pressure, and SCT were measured and compared between the two groups. Of 24 eyes with chronic RRD, 11 had primary pars plana vitrectomy...
May 19, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28527030/intravitreal-erythropoietin-injection-in-late-stage-optic-neuropathy-a-safety-study-on-human
#9
Ugur Acar, Bekir Kucuk, Mehmet Koray Sevinc, Seckin Aykas, Mesut Erdurmus, Gungor Sobaci
AIM: To evaluate the whether intravitreal erythropoietin (EPO) administration has any beneficial or adverse effect in patients with late-stage optic neuropathy (ON) or not. METHODS: The study examined 16 eyes of 16 patients who had late-stage ON and ≥1/20 best-corrected visual acuity (BCVA) in their affected eye. There were nonarteritic ischemic ON in 10 (62.5%) eyes, traumatic ON in 4 (25.0%) eyes and methanol-induced ON in 2 (12.5%) eyes. Using pars plana approach, 2000 IU/0...
May 19, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28526958/-ectopic-suprasellar-type-iia-prl-secreting-pituitary-adenoma
#10
REVIEW
Heng-Jun Zhou, De-Sheng Pan, Xiao-Qun Ba, Ren-Ya Zhan, Xiu-Jue Zheng, Yue-Hui Ma
BACKGROUND: Ectopic pituitary adenomas (EPAs) are rare, and the suprasellar cistern seems to be the most common location. At this time, no detailed original classification, diagnosis, or treatment protocols for suprasellar pituitary adenomas (SPAs) have been described. CASE DESCRIPTION: A 19-year-old man showed visual disturbances and lack of libido for 3 years, he suffered a sharp decline in vision with only light perception in the last week. Magnetic resonance imaging scans revealed a large suprasellar cystic lesion with a normal pituitary in the sella turcica...
May 19, 2017: Pituitary
https://www.readbyqxmd.com/read/28525682/secondary-sulcus-fixed-foldable-iol-implantation-with-25-g-infusion-in-patients-with-previous-ppv-after-open-globe-injury
#11
Tiangeng He, Caiyun You, Song Chen, Xiangda Meng, Yuanyuan Liu, Hua Yan
PURPOSE: To evaluate the safety and efficacy of secondary sulcus-fixed foldable intraocular lens (IOL) implantation through a clear corneal incision with 25-G infusion in patients with previous pars plana vitrectomy (PPV) after open-globe injury, and to analyze postoperative outcomes and prognostic factors of treatment. METHODS: Clinical data of 89 eyes of 89 patients with open-globe injury who underwent secondary sulcus-fixed foldable IOL implantation through a clear corneal incision with 25-G infusion after vitrectomy in our hospital between January 2008 and June 2015 were retrospectively analyzed...
May 16, 2017: European Journal of Ophthalmology
https://www.readbyqxmd.com/read/28525621/ros-induced-store-operated-ca2-entry-coupled-to-parp-1-hyperactivation-is-independent-of-parg-activity-in-necrotic-cell-death
#12
Frances M Munoz, Fengjiao Zhang, Argel Islas-Robles, Serrine S Lau, Terrence J Monks
2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of benzene and hydroquinone, generates reactive oxygen species (ROS) causing DNA strand breaks and the subsequent activation of DNA repair enzymes, including poly(ADP-ribose) polymerase (PARP)-1. Under robust oxidative DNA damage, PARP-1 is hyperactivated, resulting in the depletion of NAD+ and ATP with accompanying elevations in intracellular calcium concentrations (iCa2+), and ultimately necrotic cell death...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28524883/occurrence-rate-of-retinal-detachment-after-small-gauge-vitrectomy-for-idiopathic-epiretinal-membrane
#13
J Marie-Louise, E Philippakis, A Darugar, R Tadayoni, B Dupas
PurposeTo assess the occurrence rate of retinal detachment (RD) after small gauge vitrectomy for idiopathic epiretinal membrane (ERM).Patients and methodsRetrospective observational case series. The records of consecutive patients operated on for idiopathic ERM using small gauge pars plana vitrectomy between August 2012 and December 2014 with at least a 1-year follow-up were reviewed. All patients were contacted by phone to assess the occurrence of RD during the post-operative follow-up. The main outcome was the occurrence of RD...
May 19, 2017: Eye
https://www.readbyqxmd.com/read/28524456/endothelial-microparticles-released-by-activated-protein-c-protect-beta-cells-through-epcr-par1-and-annexin-a1-fpr2-pathways-in-islets
#14
Guillaume Kreutter, Mohamad Kassem, Ali El Habhab, Philippe Baltzinger, Malak Abbas, Julie Boisrame-Helms, Lamia Amoura, Jean Peluso, Blandine Yver, Zobairi Fatiha, Geneviève Ubeaud-Sequier, Laurence Kessler, Florence Toti
Islet transplantation is associated with early ischaemia/reperfusion, localized coagulation and redox-sensitive endothelial dysfunction. In animal models, islet cytoprotection by activated protein C (aPC) restores islet vascularization and protects graft function, suggesting that aPC triggers various lineages. aPC also prompts the release of endothelial MP that bear EPCR, its specific receptor. Microparticles (MP) are plasma membrane procoagulant vesicles, surrogate markers of stress and cellular effectors...
May 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28523947/potentiation-of-trap-6-induced-platelet-dense-granule-release-by-blockade-of-p2y12-signaling-with-mrs2395
#15
Annachiara Mitrugno, Rachel A Rigg, Nicole B Laschober, Anh T P Ngo, Jiaqing Pang, Craig D Williams, Joseph E Aslan, Owen J T McCarty
The release of ADP from platelet dense granules and its binding to platelet P2Y12 receptors is key to amplifying the initial hemostatic response and propagating thrombus formation. P2Y12 has thus emerged as a therapeutic target to safely and effectively prevent secondary thrombotic events in patients with acute coronary syndrome or a history of myocardial infarction. Pharmacological inhibition of P2Y12 receptors represents a useful approach to better understand the signaling mediated by these receptors and to elucidate the role of these receptors in a multitude of platelet hemostatic and thrombotic responses...
May 19, 2017: Platelets
https://www.readbyqxmd.com/read/28522388/trends-in-socioeconomic-costs-of-morbid-obesity-among-korean-adults-2009-2013-data-from-national-health-insurance-service
#16
Jae-Woo Lee, Young-Eun Choi, Dong-Wook Kim, Sunmi Lee, Kyung-Hee Cho
As the prevalence of morbid obesity increased in Korea, the estimation of the accurate socioeconomic costs by morbid obesity was required; we analysed national medical costs through the big data. From 2009 year to 2013 year, Direct Costs (DC) for medical costs, transit costs and nursing costs and Indirect Costs (IC) for Future Income Loss (FIL) and Productivity Loss (PL) of morbid obesity (BMI≥30) were calculated, and socioeconomic costs were estimated by applying Population Attributable Risk (PAR) proportion according to obesity related diseases...
May 15, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28521141/indirect-pathway-of-caudal-basal-ganglia-for-rejection-of-valueless-visual-objects
#17
Hyoung F Kim, Hidetoshi Amita, Okihide Hikosaka
The striatum controls behavior in two ways: facilitation and suppression through the direct and indirect pathways, respectively. However, it is still unclear what information is processed in these pathways. To address this question, we studied two pathways originating from the primate caudate tail (CDt). We found that the CDt innervated the caudal-dorsal-lateral part of the substantia nigra pars reticulata (cdlSNr), directly or indirectly through the caudal-ventral part of the globus pallidus externus (cvGPe)...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28516446/a-primary-human-lung-alveolus-on-a-chip-model-of-intravascular-thrombosis-for-assessment-of-therapeutics
#18
Abhishek Jain, Riccardo Barrile, Andries D van der Meer, Akiko Mammoto, Tadanori Mammoto, Karen De Ceunynck, Omozuanvbo Aisiku, Monicah A Otieno, Calvert S Louden, Geraldine A Hamilton, Robert Flaumenhaft, Donald E Ingber
Pulmonary thrombosis is a significant cause of patient mortality, however, there are no effective in vitro models of thrombi formation in human lung microvessels, that could also assess therapeutics and toxicology of antithrombotic drugs. Here we show that a microfluidic lung alveolus-on-a-chip lined by human primary alveolar epithelium interfaced with endothelium, and cultured under flowing whole blood can be used to perform quantitative analysis of organ-level contributions to inflammation-induced thrombosis...
May 17, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28516282/region-specific-iron-measured-by-mri-as-a-biomarker-for-parkinson-s-disease
#19
REVIEW
Xiaojun Guan, Xiaojun Xu, Minming Zhang
The identification of sensitive and specific biomarkers for Parkinson's disease (PD) poses an important clinical challenge. A potential biomarker for early diagnosis and disease monitoring of PD is region-specific iron. Iron accumulation in the substantia nigra pars compacta is considered a main characteristic of PD. However, questions remain, such as the relationship between nigral iron and clinical indices of PD (motor impairment or disease duration). Further, previous studies have suggested the influence of iron on other nuclei...
May 17, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28516119/affinity-pulldown-of-biotinylated-rna-for-detection-of-protein-rna-complexes
#20
Amaresh C Panda, Jennifer L Martindale, Myriam Gorospe
RNA-binding proteins (RBPs) have recently emerged as crucial players in the regulation of gene expression. The interactions of RBPs with target mRNAs control the levels of gene products by altering different regulatory steps, including pre-mRNA splicing and maturation, nuclear mRNA export, and mRNA stability and translation (Glisovic et al., 2008). There are several methodologies available today to identify RNAs bound to specific RBPs; some detect only recombinant molecules in vitro, others detect recombinant and endogenous molecules, while others detect only endogenous molecules...
December 20, 2016: Bio-protocol
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