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https://www.readbyqxmd.com/read/28088772/thrombospondin-immune-regulation-and-the-kidney
#1
Claudio Ponticelli, Hans-Joachim Anders
Most therapeutic attempts to prevent the progression of kidney diseases have been based on interventions to inhibit the production of transforming growth factor-β (TGF-β). Thrombospondins (TSPs) play an important role in activating TGF-β. In the healthy kidney, two TSPs are expressed, TSP1 and TSP2, which exert contrasting effects. While TSP1 is a major activator of TGF-β in renal cells and exerts pro-inflammatory effects both in vitro and in vivo, TSP2 lacks the ability for TGF-β activation but regulates matrix remodeling and inflammation in experimental kidney disease...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28088735/long-non-coding-rna-ccat1-promotes-human-retinoblastoma-so-rb50-and-y79-cells-through-negative-regulation-of-mir-218-5p
#2
Hongxu Zhang, Jianguang Zhong, Zhenyu Bian, Xiang Fang, You Peng, Yongping Hu
OBJECTIVE: To investigate the regulatory role and potential mechanism of long non-coding RNAs (lncRNA) in human retinoblastoma (RB). METHODS: The lncRNA profile in RB tissues were analyzed by microarray and quantitative reverse transcription PCR (qRT-PCR). One of the identified lncRNAs (LncRNA CCAT1) was selected for further experiments. SO-RB50 and Y79 cells were transfected with negative control, siRNA targeting lncRNA CCAT1 (si-CCAT1) and si-CCAT1+miR218-5p inhibitor, respectively...
January 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28088637/multi-scale-control-influences-sense-of-agency-investigating-intentional-binding-using-event-control-approach
#3
Devpriya Kumar, Narayanan Srinivasan
Control exercised by humans through interactions with the environment is critical for sense of agency. Here, we investigate how control at multiple levels influence implicit sense of agency measured using intentional binding. Participants are asked to hit a moving target using a joystick with noisy control followed by an intentional binding task initiated by the target hitting action. Perceptual-motor level control was manipulated through noise in the joystick controller (experiment 1) and goal-level control in terms of feedback about successful hit (experiments 2a and 2b)...
January 12, 2017: Consciousness and Cognition
https://www.readbyqxmd.com/read/28088635/mucoadhesive-amorphous-solid-dispersions-for-sustained-release-of-poorly-water-soluble-drugs
#4
Justin S LaFountaine, Leena Kumari Prasad, Dave A Miller, James W McGinity, Robert O Williams
The oral delivery of mucoadhesive patches has been shown to enhance the absorption of large molecules such as peptides. We hypothesized that this mechanism could have utility for poorly soluble small molecules by utilizing a mucoadhesive polymer as the matrix for an amorphous solid dispersion. Binary dispersions of itraconazole and carbomer (Carbopol 71G) were prepared utilizing a thermokinetic mixing process (KinetiSol Dispersing) and the physicochemical properties were investigated by powder x-ray diffraction, calorimetry, and liquid chromatography...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28088612/alterations-in-cytokine-gene-expression-profile-in-colon-mucosa-of-inflammatory-bowel-disease-patients-on-different-therapeutic-regimens
#5
Tsvetelina Velikova, Dobroslav Kyurkchiev, Zoya Spassova, Iliya Karakolev, Ekaterina Ivanova-Todorova, Iskra Altankova, Spaska Stanilova
Inflammatory bowel disease (IBD) is assumed to be caused by genetic and environmental factors that interact together in promoting intestinal immune dysregulation where cytokines have validated role. However, the underlying intimate mechanisms in the human IBD involving cytokines still needs to be supplemented especially in the clinical context. The aim of this study was to investigate the expression of some inflammatory and regulatory cytokines (IL-17A, IL-23, IL-6, TGFβ1, and IL-10) as well as of the transcription factor FoxP3 in mucosal samples of IBD and non-IBD patients...
January 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28088550/novel-involvement-of-mir-522-3p-in-high-mobility-group-box-1-induced-prostaglandin-reductase-1-expression-and-reduction-of-phagocytosis
#6
Gyeoung-Jin Kang, Hye-Ja Lee, Hyun Jung Byun, Eun Ji Kim, Hyun Ji Kim, Mi Kyung Park, Chang-Hoon Lee
Resolution of inflammation is important for physiological homeostasis. Chronic inflammatory diseases may be caused by abnormal resolution of inflammation. However, what causes a failure of inflammatory resolution is unclear. Here we investigated the involvement of high mobility group box 1 (HMGB1) protein in the control of inflammatory resolution as a 'anti-resolution factor'. We first confirmed the increased expression of HMGB1 and prostaglandin reductase 1 (PTGR1) in inflammatory conditions and HMGB1-mediated regulation of the expression of PTGR1...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088518/s100a8-protein-attenuates-airway-hyperresponsiveness-by-suppressing-the-contraction-of-airway-smooth-muscle
#7
Yu-Dong Xu, Yu Wang, Lei-Miao Yin, Gyoung-Hee Park, Luis Ulloa, Yong-Qing Yang
Airway hyperresponsiveness (AHR) is a major clinical problem in allergic asthma mainly caused by the hypercontractility of airway smooth muscles (ASM). S100A8 is an important member of the S100 calcium-binding protein family with a potential to regulate cell contractility. Here, we analyze the potential of S100A8 to regulate allergen-induced AHR and ASM contraction. Treatment with recombinant S100A8 (rS100A8) diminished airway hyperresponsiveness in OVA-sensitized rats. ASM contraction assays showed that rS100A8 reduced hypercontractility in both isolated tracheal rings and primary ASM cells treated by acetylcholine...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28088487/adenosine-receptors-and-caffeine-in-retinopathy-of-prematurity
#8
REVIEW
Jiang-Fan Chen, Shuya Zhang, Rong Zhou, Zhenlang Lin, Xiaohong Cai, Jing Lin, Yuqin Huo, Xiaoling Liu
Retinopathy of prematurity (ROP) is a major cause of childhood blindness in the world and is caused by oxygen-induced damage to the developing retinal vasculature, resulting in hyperoxia-induced vaso-obliteration and subsequent delayed retinal vascularization and hypoxia-induced pathological neovascularization driven by vascular endothelial growth factor (VEGF) signaling pathway in retina. Current anti-VEGF therapy has shown some effective in a clinical trial, but is associated with the unintended effects on delayed eye growth and retinal vasculature development of preterm infants...
January 11, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28088361/purification-and-characterisation-of-dsrna-using-ion-pair-reverse-phase-chromatography-and-mass-spectrometry
#9
Alison O Nwokeoji, An-Wen Kung, Peter M Kilby, David E Portwood, Mark J Dickman
RNA interference has provided valuable insight into a wide range of biological systems and is a powerful tool for the analysis of gene function. The exploitation of this pathway to block the expression of specific gene targets holds considerable promise for the development of novel RNAi-based insect management strategies. In addition, there are a wide number of future potential applications of RNAi to control agricultural insect pests as well as its use for prevention of diseases in beneficial insects. The potential to synthesise large quantities of dsRNA by in-vitro transcription or in bacterial systems for RNA interference applications has generated significant demand for the development and application of high throughput analytical tools for the rapid extraction, purification and analysis of dsRNA...
December 21, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28088355/kir-genes-and-hla-class-i-ligands-in-a-caucasian-brazilian-population-with-colorectal-cancer
#10
Pâmela Portela, Joice Merzoni, Juliana D Lindenau, Daniel C Damin, Timothy John Wilson, Rafael Roesler, Gilberto Schwartsmann, Luiz Mariana Fernando Jobim Jobim
Colorectal cancer (CRC) can occur anywhere in the colon or rectum and represents the third most common cancer in the world in both sexes. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA ligands in patients with colorectal cancer and healthy controls. We examined the polymorphism of 16 KIR genes and their HLA ligands in 154 caucasoid CRC patients and 216 controls...
January 11, 2017: Human Immunology
https://www.readbyqxmd.com/read/28088233/successful-recovery-from-a-subclavicular-ulcer-caused-by-lenvatinib-for-thyroid-cancer-a-case-report
#11
Morimasa Kitamura, Tomomasa Hayashi, Chiaki Suzuki, Shigeru Hirano, Ichiro Tateya, Yo Kishimoto, Koichi Omori
BACKGROUND: There are currently no effective therapeutic methods for locally recurrent, metastatic, or progressive radioactive iodine (RAI)-refractory differentiated thyroid cancer. However, multitargeted tyrosine kinase inhibitors (TKIs) such as lenvatinib or sorafenib have been approved for patients with RAI-refractory differentiated thyroid cancer as a second targeted therapy, and these agents can prolong patient survival. However, several cases have been reported that TKIs have caused fatal complications such as fistula formation or bleeding...
January 14, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28088015/transferrin-gated-mesoporous-silica-nanoparticles-for-redox-responsive-and-targeted-drug-delivery
#12
Xiaolu Chen, Hui Sun, Jun Hu, Xia Han, Honglai Liu, Ying Hu
This work reports on a targeted and controlled drug delivery system based on protein decorated mesoporous silica nanoparticles (MSNs). In this system, transferrin (Tf), a naturally existing protein, is grafted on the surfaces of MSNs via redox-cleavable disulfide bonds, serving as both a capping agent and a targeting ligand simultaneously. The uniform particles with ordered mesoporous structures and the successful construction of the Tf/MSN hybrid nanocarriers can be confirmed through combined techniques. It is found that the model anticancer drug doxorubicin (DOX) can be efficiently encapsulated in the MSNs in the absence of glutathione (GSH), and a burst release of DOX is observed when the system is exposed to GSH, indicating good capping efficiency of Tf and redox-responsive release of DOX...
January 8, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28087825/incidence-and-predictors-of-epilepsy-after-pediatric-arterial-ischemic-stroke
#13
Lori L Billinghurst, Lauren A Beslow, Nicholas S Abend, Michael Uohara, Laura Jastrzab, Daniel J Licht, Rebecca N Ichord
OBJECTIVE: To determine the cumulative incidence and clinical predictors of remote symptomatic seizures and epilepsy after pediatric arterial ischemic stroke (AIS). METHODS: We performed a retrospective analysis of 218 participants with neonatal AIS (NAIS), presumed perinatal AIS (PPAIS), and childhood AIS (CAIS) from a single-center prospective consecutive cohort enrolled from 2006 to 2014. Medical records were reviewed for timing, semiology, and treatment of acute symptomatic seizures, remote symptomatic seizures (RSS), and epilepsy...
January 13, 2017: Neurology
https://www.readbyqxmd.com/read/28087810/akt1-lkb1-and-yap1-revealed-as-myc-interactors-with-nanoluc-based-protein-fragment-complementation-assay
#14
Xiu-Lei Mo, Qi Qi, Andrei A Ivanov, Qiankun Niu, Yin Luo, Jonathan Havel, Russell Goetze, Sydney Bell, Carlos S Moreno, Lee A D Cooper, Margaret A Johns, Fadlo R Khuri, Yuhong Du, Haian Fu
The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. Here we report the development of a NanoLuc®-based protein-fragment complementation assay (NanoPCA) and mapping of the MYC protein interaction hub in live mammalian cells. The NanoPCA system was configured to enable detection of protein-protein interactions (PPI) at the endogenous level, as shown with PRAS40 dimerization, and detection of weak interactions, such as PINCH1-NCK2...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28087767/trial-by-trial-motor-cortical-correlates-of-a-rapidly-adapting-visuomotor-internal-model
#15
Sergey D Stavisky, Jonathan C Kao, Stephen I Ryu, Krishna V Shenoy
: Accurate motor control is mediated by internal models of how neural activity generates movement. We examined neural correlates of an adapting internal model of visuomotor gain in motor cortex while two macaques performed a reaching task in which the gain scaling between the hand and a presented cursor was varied. Previous studies of cortical changes during visuomotor adaptation focused on preparatory and peri-movement epochs and analyzed trial-averaged neural data. Here, we recorded simultaneous neural population activity using multielectrode arrays and focused our analysis on neural differences in the period before the target appeared...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28087766/control-of-amygdala-circuits-by-5-ht-neurons-via-5-ht-and-glutamate-co-transmission
#16
Ayesha Sengupta, Marco Bocchio, David M Bannerman, Trevor Sharp, Marco Capogna
: The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Thus, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin (ChR2) genetically targeted to 5-HT neurons...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28087752/deficient-retinoid-driven-angiogenesis-may-contribute-to-failure-of-adult-human-lung-regeneration-in-emphysema
#17
John-Poul Ng-Blichfeldt, Joana Alçada, M Angeles Montero, Charlotte H Dean, Uta Griesenbach, Mark J Griffiths, Matthew Hind
BACKGROUND: Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. OBJECTIVES: To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema...
January 13, 2017: Thorax
https://www.readbyqxmd.com/read/28087735/relationships-linking-emotional-motor-cognitive-and-gabaergic-dysfunctions-in-dystrophin-deficient-mdx-mice
#18
Cyrille Vaillend, Rémi Chaussenot
Alterations in the Duchenne muscular dystrophy (DMD) gene have been associated with enhanced stress reactivity in vertebrate species, suggesting a role for brain dystrophin in fear-related behavioral and cognitive processes. Because the loss of dystrophin (Dp427) reduces clustering of central GABAA receptors, it is suspected that local inhibitory tuning and modulation of neuronal excitability are perturbed in a distributed brain circuit that normally controls such critical behavioral functions. In this study we undertook a large-scale behavioral study to evaluate fear-related behavioral disturbances in dystrophin-deficient mdx mice...
January 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28087725/neurodevelopmental-outcomes-of-extremely-low-birthweight-infants-randomised-to-different-pco2-targets-the-phelbi-follow-up-study
#19
Ulrich H Thome, Orsolya Genzel-Boroviczeny, Bettina Bohnhorst, Manuel Schmid, Hans Fuchs, Oliver Rohde, Stefan Avenarius, Hans-Georg Topf, Andrea Zimmermann, Dirk Faas, Katharina Timme, Barbara Kleinlein, Horst Buxmann, Wilfried Schenk, Hugo Segerer, Norbert Teig, Annett Bläser, Roland Hentschel, Matthias Heckmann, Rolf Schlösser, Jochen Peters, Rainer Rossi, Wolfgang Rascher, Ralf Böttger, Jürgen Seidenberg, Gesine Hansen, Maria Zernickel, Harald Bode, Jens Dreyhaupt, Rainer Muche, Helmut D Hummler
BACKGROUND: Tolerating higher partial pressures of carbon dioxide (PCO2) in mechanically ventilated extremely low birthweight infants to reduce ventilator-induced lung injury may have long-term neurodevelopmental side effects. This study analyses the results of neurodevelopmental follow-up of infants enrolled in a randomised multicentre trial. METHODS: Infants (n=359) between 400 and 1000 g birth weight and 23 0/7-28 6/7 weeks gestational age who required endotracheal intubation and mechanical ventilation within 24 hours of birth were randomly assigned to high PCO2 or to a control group with mildly elevated PCO2 targets...
January 13, 2017: Archives of Disease in Childhood. Fetal and Neonatal Edition
https://www.readbyqxmd.com/read/28087701/the-ubiquitin-ligase-nedd4l-regulates-the-na-k-2cl-co-transporter-nkcc1-slc12a2-in-the-colon
#20
Chong Jiang, Hiroshi Kawabe, Daniela Rotin
The ubiquitin ligase Nedd4-like (Nedd4L, or Nedd4-2) binds to and regulates stability of the epithelial Na+ channel (ENaC) in salt absorbing epithelia in the kidney, lung, and other tissues. Its role in the distal colon, which also absorbs salt and fluid and expresses ENaC, is unknown. Using conditional knockout approach to knockout Nedd4L in mice intestinal epithelium (Nedd4Lf/f;Vil-CreERT2) we show here that Nedd4L depletion leads to a higher steady-state short circuit current (Isc) in mouse distal colon tissue relative to controls...
January 13, 2017: Journal of Biological Chemistry
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