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Simon Schimmack, Sarah Kneller, Nigora Dadabaeva, Frank Bergmann, Andrew Taylor, Thilo Hackert, Jens Werner, Oliver Strobel
BACKGROUND: The Hedgehog (HH) pathway is a mediator in pancreatic ductal adenocarcinoma (PDAC). Surprisingly, previous studies suggested that primary cilia (PC), the essential organelles for HH signal transduction, were lost in PDAC. The aim of this study was to determine the presence of PC in human normal pancreas, chronic pancreatitis, and during carcinogenesis to PDAC with focus on both epithelia and stroma. METHODS: PC were analyzed in paraffin sections from normal pancreas, chronic pancreatitis, intraductal papillary-mucinous neoplasia, and PDAC, as well as in primary human pancreatic stellate cells (PSC) and pancreatic cancer cell lines by double immunofluorescence staining for acetylated α-tubuline and γ-tubuline...
2016: PloS One
Eva C Thoma, Tobias Heckel, David Keller, Nicolas Giroud, Brian Leonard, Klaus Christensen, Adrian Roth, Cristina Bertinetti-Lapatki, Martin Graf, Christoph Patsch
Due to their broad differentiation potential, pluripotent stem cells (PSCs) offer a promising approach for generating relevant cellular models for various applications. While human PSC-based cellular models are already advanced, similar systems for non-human primates (NHPs) are still lacking. However, as NHPs are the most appropriate animals for evaluating the safety of many novel pharmaceuticals, the availability of in vitro systems would be extremely useful to bridge the gap between cellular and animal models...
October 25, 2016: Scientific Reports
Sawanta S Mali, Hyungjin Kim, Sang Eun Shim, Chang Kook Hong
Here we report a solution processed nanostructured NiO as a hole transport layer (HTL) for efficient inverted MAPb(I1-xBrx)3 (x = 0.3) perovskite solar cells (PSCs). The best performing p-i-n PSC exhibits 15.35% power conversion efficiency with a current density (JSC) of 19.85 mA cm(-2), an open circuit voltage (VOC) of 1.056 V and a fill factor (FF) of 0.73. The developed method is simple and cost effective.
October 25, 2016: Nanoscale
Richard Baumgartner, William Cho, Alexandre Coimbra, Christopher Chen, Zaiqi Wang, Arie Struyk, Narayanaswamy Venketasubramanian, May Low, Cindy Gargano, Fuqiang Zhao, Donald Williams, Torsten Reese, Stephanie Seah, Dai Feng, Sonya Apreleva, Esben Petersen, Jeffrey L Evelhoch
PURPOSE: To present the testretest and contrast dose effect results of cerebral blood volume (CBV) functional MRI (fMRI) in healthy human volunteers using ferumoxytol (Feraheme), an ultrasmall-superparamagnetic iron oxide (USPIO) nanoparticle. MATERIALS AND METHODS: This was an open-label, two-period, fixed-sequence study in healthy young volunteers. In eight subjects, using a 3 Tesla field strength system, blood oxygen level dependent (BOLD) and CBV fMRI were acquired in response to a visual black-and-white checkboard stimulation paradigm using an escalating ferumoxytol dose design (250, 350, and 510 mg iron)...
October 24, 2016: Journal of Magnetic Resonance Imaging: JMRI
Hung-Yi Liu, Tanja Greene, Tsai-Yu Lin, Camron S Dawes, Murray Korc, Chien-Chi Lin
: The complex network of biochemical and biophysical cues in the pancreatic desmoplasia not only presents challenges to the fundamental understanding of tumor progression, but also hinders the development of therapeutic strategies against pancreatic cancer. Residing in the desmoplasia, pancreatic stellate cells (PSCs) are the major stromal cells affecting the growth and metastasis of pancreatic cancer cells by means of paracrine effects and extracellular matrix protein deposition. PSCs remain in a quiescent/dormant state until they are 'activated' by various environmental cues...
October 18, 2016: Acta Biomaterialia
B Eksteen, J Heatherington, J Oshiomogo, R Panaccione, G Kaplan, S Ghosh
This article has been retracted: please see Elsevier Policy on Article Withdrawal ( The abstract authors and presenters of PS124 - EFFICACY AND SAFETY OF INDUCTION DOSING OF VEDOLIZUMAB FOR REDUCING BILIARY INFLAMMATION IN PRIMARY SCLEROSING CHOLANGITIS (PSC) IN INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE submitted and presented at ILC 2016 have raised concerns that the source data in some cases are inconsistent and requires further evaluation to determine the true magnitude of effect...
2016: Journal of Hepatology
Ido Sagi, Dieter Egli, Nissim Benvenisty
Haploid human pluripotent stem cells (PSCs) integrate haploidy and pluripotency, providing a novel system for functional genomics and developmental research in humans. We have recently derived haploid human embryonic stem cells (ESCs) by parthenogenesis and demonstrated their wide differentiation potential and applicability for genetic screening. Because haploid cells can spontaneously become diploid, their enrichment at an early passage is key for successful derivation. In this protocol, we describe two methodologies, namely metaphase spread analysis and cell sorting, for the identification of haploid human cells within parthenogenetic ESC lines...
November 2016: Nature Protocols
Leonardo Romorini, Ximena Garate, Gabriel Neiman, Carlos Luzzani, Verónica Alejandra Furmento, Alejandra Sonia Guberman, Gustavo Emilio Sevlever, María Elida Scassa, Santiago Gabriel Miriuka
Human embryonic and induced pluripotent stem cells are self-renewing pluripotent stem cells (PSC) that can differentiate into a wide range of specialized cells. Basic fibroblast growth factor is essential for PSC survival, stemness and self-renewal. PI3K/AKT pathway regulates cell viability and apoptosis in many cell types. Although it has been demonstrated that PI3K/AKT activation by bFGF is relevant for PSC stemness maintenance its role on PSC survival remains elusive. In this study we explored the molecular mechanisms involved in the regulation of PSC survival by AKT...
October 20, 2016: Scientific Reports
Jacqueline Jossen, Rachel Annunziato, Hee-Sung Kim, Jaime Chu, Ronen Arnon
OBJECTIVES: Autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are progressive immune-mediated inflammatory diseases that may require liver transplant (LT). Outcomes in children undergoing LT for these diseases are poorly studied in the Pediatric End Stage Liver Disease (PELD) era. We aimed to characterize the outcome of LT in children with AIH and PSC. METHODS: Children ≤18 years with PSC or AIH who had a first, isolated LT from 2002-2012 were identified from the UNOS database...
October 13, 2016: Journal of Pediatric Gastroenterology and Nutrition
Ashwani K Singal, Xiao Fang, Mohamed Kaif, Mohsen Hasanin, Brendan M Mcguire, Yong-Fang Kuo, Russell H Wiesner
MAIN PROBLEM: Patients with primary sclerosing cholangitis (PSC) have frequent episodes of cholangitis with potential for high mortality while waiting for liver transplantation. However, data on wait-list mortality specific to liver disease etiology are limited. RESULTS: Using UNOS database (2002-2013), of 81,592 listed patients, 11284 (13.8%) died waiting for transplant. Primary biliary cirrhosis (PBC) patients (N=3491) compared to PSC (N=4905) differed for age (56 vs...
October 18, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Yuan Seng Wu, Ivy Chung, Won Fen Wong, Atsushi Masamune, Maw Shin Sim, Chung Yeng Looi
BACKGROUND: We previously showed that pancreatic stellate cells (PSC) secreted interleukin (IL)-6 and promoted pancreatic ductal adenocarcinoma (PDAC) cell proliferation via nuclear factor erythroid 2 (Nrf2)-mediated metabolic reprogramming. Epithelial-mesenchymal transition (EMT) is a key process for the metastatic cascade. To study the mechanism of PDAC progression to metastasis, we investigated the role of PSC-secreted IL-6 in activating EMT and the involvement of Nrf2 in this process...
October 14, 2016: Biochimica et Biophysica Acta
Anne M Boonstra, Roy E Stewart, Albère J A Köke, René F A Oosterwijk, Jeannette L Swaan, Karlein M G Schreurs, Henrica R Schiphorst Preuper
Objectives: The 0-10 Numeric Rating Scale (NRS) is often used in pain management. The aims of our study were to determine the cut-off points for mild, moderate, and severe pain in terms of pain-related interference with functioning in patients with chronic musculoskeletal pain, to measure the variability of the optimal cut-off points, and to determine the influence of patients' catastrophizing and their sex on these cut-off points. Methods: 2854 patients were included. Pain was assessed by the NRS, functioning by the Pain Disability Index (PDI) and catastrophizing by the Pain Catastrophizing Scale (PCS)...
2016: Frontiers in Psychology
Thomas V Kodankandath, Paul Wright, Paul M Power, Marcella De Geronimo, Richard B Libman, Thomas Kwiatkowski, Jeffrey M Katz
BACKGROUND AND OBJECTIVE: The transfer of acute ischemic stroke (AIS) patients to a comprehensive stroke center (CSC) must be rapid. Delays pose an obstacle to time-sensitive stroke treatments and, therefore, increase the likelihood of exclusion from endovascular stroke therapy. This study aims to evaluate the impact of the Stroke Rescue Program, with its goal of minimizing interfacility transfer delays and increasing the number of transport times completed within 60 minutes. METHODS: The Stroke Rescue Program was initiated to facilitate the rapid transfer of AIS patients from regional primary stroke centers (PSCs) to the network's CSC...
October 12, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Cynthia Buness, Keith D Lindor, Tamir Miloh
Primary sclerosing cholangitis (PSC), a rare progressive liver disease characterized by cholestasis and bile duct fibrosis, has no accepted, effective therapy known to delay or arrest its progression. We report a 15 year old female patient diagnosed with PSC and moderate chronic active ulcerative colitis (UC) who achieved normalization of her liver enzymes and bile ducts, and resolution of her UC symptoms with colonic mucosal healing, after treatment with a single drug therapy of the antibiotic oral vancomycin...
September 2016: Pediatric Gastroenterology, Hepatology & Nutrition
Shi Wun Tong, Janardhan Balapanuru, Deyi Fu, Kian Ping Loh
In the short time since its discovery, perovskite solar cells (PSCs) have attained high power conversion efficiency but their lack of thermal stability remains a barrier to commercialization. Among the experimentally accessible parameter space for optimizing performance, identifying an electron transport layer (ETL) that forms a thermally stable interface with perovskite and which is solution-processible at low-temperature will certainly be advantageous. Herein, we developed a mesoporous graphene/polymer composite with these advantages when used as ETL in CH3NH3PbI3 PSCs, and a high efficiency of 13...
October 12, 2016: ACS Applied Materials & Interfaces
Rodrigo Liberal, Charlotte R Grant
Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues...
October 8, 2016: World Journal of Hepatology
Seung-Ju Cho, So-Yeon Kim, Soon-Jung Park, Naree Song, Haw-Young Kwon, Nam-Young Kang, Sung-Hwan Moon, Young-Tae Chang, Hyuk-Jin Cha
Pluripotent stem cells (PSC) are promising resources for regeneration therapy, but teratoma formation is one of the critical problems for safe clinical application. After differentiation, the precise detection and subsequent elimination of undifferentiated PSC is essential for teratoma-free stem cell therapy, but a practical procedure is yet to be developed. CDy1, a PSC specific fluorescent probe, was investigated for the generation of reactive oxygen species (ROS) and demonstrated to induce selective death of PSC upon visible light irradiation...
September 28, 2016: ACS Central Science
Hanno Ehlken, Raluca Wroblewski, Christophe Corpechot, Lionel Arrivé, Tim Rieger, Johannes Hartl, Susanne Lezius, Peter Hübener, Kornelius Schulze, Roman Zenouzi, Marcial Sebode, Moritz Peiseler, Ulrike W Denzer, Alexander Quaas, Christina Weiler-Normann, Ansgar W Lohse, Olivier Chazouilleres, Christoph Schramm
BACKGROUND: Patients with primary sclerosing cholangitis (PSC) develop progressive liver fibrosis and end-stage liver disease. Non-invasive and widely available parameters are urgently needed to assess disease stage and the risk of clinical progression. Transient elastography (TE) has been reported to predict fibrosis stage and disease progression. However, these results have not been confirmed in an independent cohort and comparison of TE measurement to other non-invasive means is missing...
2016: PloS One
T Kastinen, M Niskanen, C Risko, O Cramariuc, T I Hukka
Here, we investigate the effects of both tuning the range-separation parameter of long-range corrected (LRC) density functionals and including dispersion corrections on describing the local optoelectronic properties of polymer-fullerene interfaces that are critical to the performance of polymer solar cells (PSCs). Focusing on recently studied (Chen, et al., Chem. Mater., 2012, 24, 4766-4772) PSC active layers derived from poly(benzodithiophene-co-quinoxaline) and substituted fullerene PC71BM, we compare the performance of global hybrid functionals (B3LYP and B3LYP-D) alongside two LRC functionals (ωB97X and ωB97X-D) and their optimally tuned (OT) analogs (OT-ωB97X and OT-ωB97X-D)...
October 5, 2016: Physical Chemistry Chemical Physics: PCCP
Melani Sooriyaarachchi, Graham N George, Ingrid J Pickering, Aru Narendran, Jürgen Gailer
Numerous in vivo studies have shown that the severe toxic side-effects of intravenously administered cisplatin can be significantly reduced by the co-administration of sulfur-containing 'chemoprotective agents'. Using a metallomics approach, a likely biochemical basis for these potentially useful observations was only recently uncovered and appears to involve the reaction of chemoprotective agents with cisplatin-derived Pt-species in human plasma to form novel platinum-sulfur complexes (PSC's). We here reveal aspects of the structure of two PSC's and establish the identification of an optimal chemoprotective agent to ameliorate the toxic side-effects of cisplatin, while leaving its antineoplastic activity largely intact, as a feasible research strategy to transform cisplatin into a safer and more effective anticancer drug...
October 10, 2016: Metallomics: Integrated Biometal Science
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