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Kouichi Sakamoto, Ngin Cin Khai, Yuqing Wang, Rie Irie, Hideo Takamatsu, Hiroshi Matsufuji, Ken-Ichiro Kosai
In contrast to hepatocyte growth factor (HGF), the therapeutic potential and pathophysiologic roles of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in liver diseases remain relatively unknown. To address the lack of effective pharmacologic treatments for cholestatic liver injuries, as well as to clarify the biologic features of these growth factors, we explored the effects of HB-EGF and HGF in mice with cholestatic liver injury induced by bile duct ligation (BDL). The mice were assessed 3, 5 and/or 14 days after BDL (acute, subacute and/or chronic phases, respectively) and intravenous injection of adenoviral vector expressing LacZ (control), HB-EGF, HGF, or HB-EGF and HGF...
October 20, 2016: International Journal of Molecular Medicine
Ygal Rotenstreich, Adi Tzameret, Sapir E Kalish, Ettel Bubis, Michael Belkin, Iris Moroz, Mordechai Rosner, Itay Levy, Shlomo Margel, Ifat Sher
PURPOSE: To investigate the feasibility and safety of a novel minimally invasive adjustable-depth blunt injector for pharmaceuticals delivery into the posterior segment. METHODS: Indocyanine green (ICG), sodium fluorescein and iron oxide nanoparticles (IONPs) were injected using the new injector into the extravascular spaces of the choroid (EVSC) compartment of rabbits and cadaver pig eyes. Spectral domain optical coherence tomography (SD-OCT), fundus imaging and histology analysis were performed for assessment of injection safety and efficacy...
October 25, 2016: Acta Ophthalmologica
Patrick Antonietti, Benedikt Linder, Stephanie Hehlgans, Iris C Mildenberger, Michael C Burger, Simone Fulda, Joachim P Steinbach, Florian Gessler, Franz Rodel, Michel Mittelbronn, Donat Kogel
Malignant gliomas exhibit a high intrinsic resistance against stimuli triggering apoptotic cell death. HSF1 (heat shock factor 1) acts as transcription factor upstream of HSP70 and the HSP70 co-chaperone BAG3 that is overexpressed in glioblastoma. To specifically target this resistance mechanism, we applied the selective HSF1 inhibitor KRIBB11 and the HSP70/BAG3 interaction inhibitor YM-1 in combination with the pan-Bcl-2 inhibitor AT-101. Here we demonstrate that lentiviral BAG3 silencing significantly enhances AT-101-induced cell death and reactivates effector caspase-mediated apoptosis in U251 glioma cells with high BAG3 expression, while these sensitizing effects were less pronounced in U343 cells expressing lower BAG3 levels...
October 24, 2016: Molecular Cancer Therapeutics
Ann Meulders, Michel Meulders, Iris Stouten, Jozef De Bie, Johan W S Vlaeyen
: Fear learning deficiencies might contribute to the development and maintenance of chronic pain disability. Fear is often not restricted to movements (conditioned stimulus=CS+) originally associated with pain (unconditioned stimulus=US), but expands to similar movements (generalization stimuli=GSs). This spreading of fear becomes dysfunctional when overgeneralization to safe stimuli occurs. More importantly, persistence of pain-related fear to GSs despite corrective feedback might even be more debilitating and maintain long-term chronic pain disability...
October 21, 2016: Journal of Pain: Official Journal of the American Pain Society
Pham Thi Kim Lien, Keiichi Izumikawa, Kei Muroi, Kaoru Irie, Yasuyuki Suda, Kenji Irie
Scd6, a yeast homologue of human RAP55, is a component of messenger ribonucleoproteins (mRNPs) that repress translation by binding to translation initiation factors, and also is a decapping activator along with the binding partners Edc3 and Dhh1. Herein, we report that Scd6 is a substrate of the intrinsic protein arginine methyltransferase, Hmt1, in budding yeast Saccharomyces cerevisiae. Mass spectrometric analysis revealed that several arginine residues within the Scd6 RGG motif, which is important for mRNA binding, were methylated in Hmt1 dependent manner...
2016: PloS One
Alessandra Imbrogno, Jennifer Biscarat, Andrea Iris Schäfer
BACKGROUND: Estrogens and their synthetic analogues are widely used as pharmaceuticals. Upon oral administration these drugs are eventually excreted via urine. The persistence of these pharmaceuticals and inefficient removal by water treatment lead to accumulation in surface water and effluents with negative effects for aquatic life and human health. METHODS: In this study, the uptake of estradiol by a combined magnetic ion exchange resin - ultrafiltration process (MIEX-UF) was investigated...
October 21, 2016: Current Pharmaceutical Design
Dayna Cenin, Peter O'Leary, Iris Lansdorp-Vogelaar, David Preen, Mark Jenkins, Eric Moses
No abstract text is available yet for this article.
October 23, 2016: Australian and New Zealand Journal of Public Health
Xia Wang, Xianghong Shan, Cheryl Y Gregory-Evans
The Pax6 transcription factor is essential for development of the brain, eye, olfactory and endocrine systems. Haploinsufficiency of PAX6 in humans and mice causes the congenital condition aniridia, with defects in each of these organs and systems. Identification of the PAX6 transcription networks driving normal development is therefore critical in understanding the pathophysiology observed with loss-of-function defects. Here we have focused on identification of the downstream targets for Pax6 in the developing iris and ciliary body, where we used laser capture microdissection in mouse eyes from E12...
October 20, 2016: Biochimica et Biophysica Acta
Cynthia Van Landingham, Kenneth A Mundt, Bruce C Allen, P Robinan Gentry
Reproducibility and transparency in scientific reporting is paramount to advancing science and providing the foundation required for sound regulation. Recent examples demonstrate that pivotal scientific findings cannot be replicated, due to poor documentation or methodological bias, sparking debate across scientific and regulatory communities. However, there is general agreement that improvements in communicating and documenting research and risk assessment methods are needed. In the case of formaldehyde, the peer-review conducted by a National Academy of Sciences (NAS) Committee questioned the approaches used by the Integrated Risk Information System (IRIS) in developing draft unit risk values...
October 19, 2016: Regulatory Toxicology and Pharmacology: RTP
Iris Navarro-Millán, Erika Darrah, Andrew O Westfall, Ted R Mikuls, Richard J Reynolds, Maria I Danila, Jeffrey R Curtis, Antony Rosen, S Louis Bridges
BACKGROUND: Evidence suggests that the presence of peptidyl arginine deiminase type 4 (PAD4) antibodies is associated with radiographic-severity rheumatoid arthritis (RA) among Caucasian patients. The presence of anti-PAD4 antibodies that were cross-reactivity against PAD3 was associated with more aggressive erosive disease (compared with the presence of anti-PAD4 antibodies without anti-PAD3 crossreactivity) in Caucasian RA patients. The objectives of this study were to determine the prevalence of serum anti-PAD4 and anti-PAD4/PAD3 cross-reactive autoantibodies in African Americans with RA and whether these antibodies associate with radiographic severity and radiographic progression...
October 22, 2016: Arthritis Research & Therapy
Yanin Suwan, Sunpong Jiamsawad, Wasu Supakontanasan, Chaiwat Teekhasaenee
BACKGROUND: To evaluate the mechanisms of acute angle-closure (AAC) other than the pupillary block using ultrasound biomicroscopy DESIGN: Retrospective chart review. PARTICIPANTS: All patients who were diagnosed with AAC in Ramathibodi Hospital, Bangkok, Thailand, between June 2011 and February 2015 were enrolled. METHODS: 72 patients who were diagnosed with AAC underwent a detailed ocular examination. The diagnosed mechanism of AAC was confirmed by UBM and ocular biometry...
October 22, 2016: Clinical & Experimental Ophthalmology
Auke B C Otten, Alphons P M Stassen, Michiel Adriaens, Mike Gerards, Richard G J Dohmen, Adriana J Timmer, Sabina J V Vanherle, Rick Kamps, Iris B W Boesten, Jo M Vanoevelen, Marc Muller, Bert Smeets
Of all pathogenic mitochondrial DNA (mtDNA) mutations in humans, ~25% is de novo, although the occurrence in oocytes has never been directly assessed. We used next generation sequencing to detect point mutations directly in the mtDNA of 3-15 individual mature oocytes and three somatic tissues from eight zebrafish females. Various statistical and biological filters allowed reliable detection of de novo variants with heteroplasmy ≥1.5%. In total, we detected 38 de novo base substitutions, but no insertions or deletions...
October 21, 2016: Genetics
George L Malcolm, Iris I A Groen, Chris I Baker
To interact with the world, we have to make sense of the continuous sensory input conveying information about our environment. A recent surge of studies has investigated the processes enabling scene understanding, using increasingly complex stimuli and sophisticated analyses to highlight the visual features and brain regions involved. However, there are two major challenges to producing a comprehensive framework for scene understanding. First, scene perception is highly dynamic, subserving multiple behavioral goals...
October 11, 2016: Trends in Cognitive Sciences
Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
October 20, 2016: JAMA Oncology
Benoît Roubinet, Mariano L Bossi, Philipp Alt, Marcel Leutenegger, Heydar Shojaei, Sebastian Schnorrenberg, Shamil Nizamov, Masahiro Irie, Vladimir N Belov, Stefan W Hell
Reversibly photoswitchable 1,2-bis(2-ethyl-6-phenyl-1-benzothiophene-1,1-dioxide-3-yl)perfluorocyclopentenes (EBT) having fluorescent "closed" forms were decorated with four or eight carboxylic groups and attached to antibodies. Low aggregation, efficient photoswitching in aqueous buffers, specific staining of cellular structures, and good photophysical properties were demonstrated. Alternating light pulses of UV and blue light induce numerous reversible photochemical transformations between two stables states with distinct structures...
October 21, 2016: Angewandte Chemie
Anne M Murray, Fang-Chi Hsu, Jeff D Williamson, R Nick Bryan, Hertzel C Gerstein, Mark D Sullivan, Michael E Miller, Iris Leng, Laura L Lovato, Lenore J Launer
AIMS/HYPOTHESIS: The Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, a double 2x2 factorial parallel-group randomised clinical trial, tested whether intensive compared with standard management of hyperglycaemia, BP or lipid levels reduced cognitive decline and brain atrophy in 2977 people with type 2 diabetes. We describe the results of the observational extension study, ACCORDION MIND ( registration no. NCT00182910), which aimed to measure the long-term effects of the three ACCORD interventions on cognitive and brain structure outcomes approximately 4 years after the trial ended...
October 20, 2016: Diabetologia
David G Cox, Elsa Curtit, Gilles Romieu, Pierre Fumoleau, Maria Rios, Hervé Bonnefoi, Thomas Bachelot, Patrick Soulié, Christelle Jouannaud, Hugues Bourgeois, Thierry Petit, Isabelle Tennevet, David Assouline, Marie-Christine Mathieu, Jean-Philippe Jacquin, Sandrine Lavau-Denes, Ariane Darut-Jouve, Jean-Marc Ferrero, Carole Tarpin, Christelle Lévy, Valérie Delecroix, Véronique Trillet-Lenoir, Oana Cojocarasu, Jérôme Meunier, Jean-Yves Pierga, Céline Faure-Mercier, Hélène Blanché, Mourad Sahbatou, Anne Boland, Delphine Bacq, Céline Besse, Jean-François Deleuze, Iris Pauporté, Gilles Thomas, Xavier Pivot
Genetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1...
October 14, 2016: Oncotarget
Xiaohong Liu, Hehua Ye, Qi Zhang, Xuan Cai, Wenjing Yu, Siyi Yu, Tianyu Wang, Wuyi Lu, Xiang Li, Peiquan Zhao
BACKGROUND: Myopia subjects usually have long axial lengths and are predisposed to deep anterior chamber depths and open angles. Jiangning eye study is a randomized, population based study in Shanghai to determine whether myopia has an effect on the prevalence of occludable angles. METHODS: A total of 2478 residents aged 50 years and over were randomly selected, and 2044 (82.5%) individuals of them participated in ophthalmic examinations between November 2012 and February 2013...
2016: PloS One
Felix Ulbrich, Kai B Kaufmann, Alexander Meske, Wolf A Lagrèze, Michael Augustynik, Hartmut Buerkle, Carlos C Ramao, Julia Biermann, Ulrich Goebel
PURPOSE: Ischemia and reperfusion injury may induce apoptosis and lead to sustained tissue damage and loss of function, especially in neuronal organs. While carbon monoxide is known to exert protective effects after various harmful events, the mechanism of carbon monoxide releasing molecules in neuronal tissue has not been investigated yet. We hypothesize that the carbon monoxide releasing molecule (CORM) ALF-186, administered after neuronal ischemia-reperfusion injury (IRI), counteracts retinal apoptosis and its involved signaling pathways and consecutively reduces neuronal tissue damage...
2016: PloS One
Luciana Nahar Dos Santos, Pedro Henrique Lopes da Silva, Iris Maria Peixoto Alvim, José Augusto da Costa Nery, Flávio Alves Lara, Euzenir Nunes Sarno, Danuza Esquenazi
In spite of hyporesponsivity to Mycobacterium leprae, borderline lepromatous (BL) patients show clinical and immunological instability, and undergo frequent acute inflammatory episodes such as type 1 reaction (T1R), which may cause nerve damages. This work focused on the participation of T cell subsets from blood and skin at T1R onset. We observed a significantly increased ex vivo frequency of both effector and memory CD4+ and CD8+ T cells in T1R group. Besides, ex vivo frequency of T cell homing receptor, the Cutaneous Leukocyte-associated Antigen (CLA) was significantly increased in T cells from T1R patients...
2016: PloS One
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