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https://www.readbyqxmd.com/read/27922338/pathophysiology-of-aortic-aneurysm-insights-from-human-genetics-and-mouse-models
#1
Nicole K Wilson, Russell A Gould, Elena Gallo MacFarlane, Mibava Leducq Consortium
Aneurysms are local dilations of an artery that predispose the vessel to sudden rupture. They are often asymptomatic and undiagnosed, resulting in a high mortality rate. The predisposition to develop thoracic aortic aneurysms is often genetically inherited and associated with syndromes affecting connective tissue homeostasis. This review discusses how elucidation of the genetic causes of syndromic forms of thoracic aortic aneurysm has helped identify pathways that contribute to disease progression, including those activated by TGF-β, angiotensin II and Notch ligands...
December 6, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27922122/identification-of-critical-paralog-groups-with-indispensable-roles-in-the-regulation-of-signaling-flow
#2
Dezso Modos, Johanne Brooks, David Fazekas, Eszter Ari, Tibor Vellai, Peter Csermely, Tamas Korcsmaros, Katalin Lenti
Extensive cross-talk between signaling pathways is required to integrate the myriad of extracellular signal combinations at the cellular level. Gene duplication events may lead to the emergence of novel functions, leaving groups of similar genes - termed paralogs - in the genome. To distinguish critical paralog groups (CPGs) from other paralogs in human signaling networks, we developed a signaling network-based method using cross-talk annotation and tissue-specific signaling flow analysis. 75 CPGs were found with higher degree, betweenness centrality, closeness, and 'bowtieness' when compared to other paralogs or other proteins in the signaling network...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922003/blood-flow-controls-bone-vascular-function-and-osteogenesis
#3
Saravana K Ramasamy, Anjali P Kusumbe, Maria Schiller, Dagmar Zeuschner, M Gabriele Bixel, Carlo Milia, Jaba Gamrekelashvili, Anne Limbourg, Alexander Medvinsky, Massimo M Santoro, Florian P Limbourg, Ralf H Adams
While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27922002/targeting-the-notch-regulated-non-coding-rna-tug1-for-glioma-treatment
#4
Keisuke Katsushima, Atsushi Natsume, Fumiharu Ohka, Keiko Shinjo, Akira Hatanaka, Norihisa Ichimura, Shinya Sato, Satoru Takahashi, Hiroshi Kimura, Yasushi Totoki, Tatsuhiro Shibata, Mitsuru Naito, Hyun Jin Kim, Kanjiro Miyata, Kazunori Kataoka, Yutaka Kondo
Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27918591/transcriptomic-analysis-of-mouse-cochlear-supporting-cell-maturation-reveals-large-scale-changes-in-notch-responsiveness-prior-to-the-onset-of-hearing
#5
Juan C Maass, Rende Gu, Tiantian Cai, Ying-Wooi Wan, Silvia C Cantellano, Joanna S T Asprer, Hongyuan Zhang, Hsin-I Jen, Renée K Edlund, Zhandong Liu, Andrew K Groves
Neonatal mouse cochlear supporting cells have a limited ability to divide and trans-differentiate into hair cells, but this ability declines rapidly in the two weeks after birth. This decline is concomitant with the morphological and functional maturation of the organ of Corti prior to the onset of hearing. However, despite this association between maturation and loss of regenerative potential, little is known of the molecular changes that underlie these events. To identify these changes, we used RNA-seq to generate transcriptional profiles of purified cochlear supporting cells from 1- and 6-day-old mice...
2016: PloS One
https://www.readbyqxmd.com/read/27918553/jagged-1-is-a-major-notch-ligand-along-cholangiocarcinoma-development-in-mice-and-humans
#6
L Che, B Fan, M G Pilo, Z Xu, Y Liu, A Cigliano, A Cossu, G Palmieri, R M Pascale, A Porcu, G Vidili, M Serra, F Dombrowski, S Ribback, D F Calvisi, X Chen
Intrahepatic cholangiocarcinoma (ICC) is a rare yet deadly malignancy with limited treatment options. Activation of the Notch signalling cascade has been implicated in cholangiocarcinogenesis. However, while several studies focused on the Notch receptors required for ICC development, little is known about the upstream inducers responsible for their activation. Here, we show that the Jagged 1 (Jag1) ligand is almost ubiquitously upregulated in human ICC samples when compared with corresponding non-tumorous counterparts...
December 5, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27917810/comparison-of-neck-ultrasonography-with-a-ph-meter-to-confirm-correct-position-of-nasogastric-tube
#7
Bunyamin Muslu, Rüveyda I Demircioglu, Muhammet Gözdemir, Burhanettin Usta
PURPOSE: The aim of this study was to compare pH meter and neck ultrasonograph for evaluation of nasogastric tube (NGT) position. METHODS: A total of 35 adult patients who required NGT insertion were included. The NGT was inserted by an anesthetist after endotracheal intubation, and the transducer was placed transversely on the neck, just superior to the suprasternal notch. The passage of the NGT in the esophagus was evaluated by a sonographer, and the stomach was emptied by nasogastric suction...
December 1, 2016: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/27917547/pituitary-stalk-interruption-syndrome-from-clinical-findings-to-pathogenesis
#8
REVIEW
Cheng-Zhi Wang, Ling-Ling Guo, Bai-Yu Han, Xing Su, Qing-Hua Guo, Yi-Ming Mu
Pituitary stalk interruption syndrome is a rare congenital defect manifesting with varying degrees of pituitary hormone deficiency. The signs and symptoms of PSIS during the neonatal period and infancy are often overlooked and therefore diagnosis is delayed. The typical manifestations of PSIS can be detected by magnetic resonance imaging. Several genes in Wnt, Notch and Shh signaling pathways related to hypothalamic-pituitary development, such as PIT1, PROP1, LHX3/LHX4, PROKR2, OTX2, TGIF and HESX1, have been found to be associated with PSIS...
December 5, 2016: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/27916152/volar-ulnar-approach-for-fixation-of-the-volar-lunate-facet-fragment-in-distal-radius-fractures-a-technical-tip
#9
REVIEW
Daniel Tordjman, Richard M Hinds, Omri Ayalon, S Steven Yang, John T Capo
The volar Henry approach is most commonly used for surgical fixation of distal radius fractures. However, this approach is limited in achieving adequate exposure for the fixation of the volar-ulnar portion of the distal radius, rendering it difficult for the ideal placement of the fixation construct. We propose the use of the extensile volar-ulnar approach for fixation of distal radius fracture involving a small volar-ulnar fragment. This approach allows optimal reduction of the sigmoid notch and the volar lunate facet, which anatomically reduces both the radiocarpal joint and the sigmoid notch...
December 2016: Journal of Hand Surgery
https://www.readbyqxmd.com/read/27916094/-knockdown-of-runx3-inhibits-hypoxia-induced-endothelial-to-mesenchymal-transition-of-human-cardiac-microvascular-endothelial-cells
#10
Yanhua Liu, Bingong Li, Yuqin Wang, Delong Wang, Jin Zou, Xuan Ke, Yanqin Hao
Objective To investigate the effects of Runt-related transcription factor 3 (RUNX3) knockdown on hypoxia-induced endothelial-to-mesenchymal transition (EndoMT) of human cardiac microvascular endothelial cells (HCMECs), and elucidate the underlying molecular mechanism. Methods HCMECs were cultured in hypoxic conditions and infected with RUNX3-RNAi lentivirus to knock-down the expression of RUNX3. Reverse transcription PCR was performed to detect the mRNA expressions of RUNX3 and EndoMT related genes such as CD31, vascular endothelial cadherin (VE-cadherin), α-smooth muscle actin (α-SMA) and fibroblast-specific protein-1 (FSP-1); Western blotting was used to determine the protein expressions of RUNX3, CD31, α-SMA and another molecules involved in EndoMT; and immunofluorescence cytochemistry was applied to observe the colocalization of CD31 and α-SMA...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27913625/absence-of-mir-146a-in-podocytes-increases-risk-of-diabetic-glomerulopathy-via-upregulation-of-erbb4-and-notch-1
#11
Ha Won Lee, Samia Q Khan, Shehryar Khaliqdina, Mehmet M Altintas, Florian Grahammer, Jimmy L Zhao, Kwihey Koh, Nicholas J Tardi, Mohd Hafeez Faridi, Terese Geraghty, David J Cimbaluk, Katalin Susztak, Luis F Moita, David Baltimore, Pierre-Louis Tharaux, Tobias B Huber, Matthias Kretzler, Markus Bitzer, Jochen Reiser, Vineet Gupta
Podocyte injury is an early event in diabetic kidney disease and is a hallmark of glomerulopathy. MicroRNA-146a (miR-146a) is highly expressed in many cell types under homeostatic conditions, and plays an important anti-inflammatory role in myeloid cells. However, its role in podocytes is unclear. Here, we show that miR-146a expression levels decrease in the glomeruli of patients with type 2 diabetes (T2D), which correlates with increased albuminuria and glomerular damage. MiR-146a levels are also significantly reduced in the glomeruli of albuminuric BTBR ob/ob mice, indicating its significant role in maintaining podocyte health...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913532/t-cell-acute-lymphoblastic-leukemia
#12
Elizabeth A Raetz, David T Teachey
T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913341/quantification-of-shear-wave-scattering-from-far-surface-defects-via-ultrasonic-wavefield-measurements
#13
Alexander J Dawson, Jennifer E Michaels, Joseph W Kummer, Thomas E Michaels
Nondestructive evaluation methods rely on prior knowledge of the expected interaction of ultrasonic waves with defects to inform detection and characterization decisions. Wavefield imaging, which refers to the measurement of signals originating from a spatially fixed source on a two-dimensional rectilinear grid, can be applied to visualize the effect of a subsurface scatterer on surface-measured wave motion. Here, obliquely-incident shear waves are directed at the far surface of a plate containing a through-hole using the well-known angle-beam ultrasonic inspection method...
December 1, 2016: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
https://www.readbyqxmd.com/read/27911371/development-of-stem-cell-derived-antigen-specific-regulatory-t-cells-against-autoimmunity
#14
Mohammad Haque, Kristin Fino, Praneet Sandhu, Jianxun Song
Autoimmune diseases arise due to the loss of immunological self-tolerance. Regulatory T cells (Tregs) are important mediators of immunologic self-tolerance. Tregs represent about 5 - 10% of the mature CD4(+) T cell subpopulation in mice and humans, with about 1 - 2% of those Tregs circulating in the peripheral blood. Induced pluripotent stem cells (iPSCs) can be differentiated into functional Tregs, which have a potential to be used for cell-based therapies of autoimmune diseases. Here, we present a method to develop antigen (Ag)-specific Tregs from iPSCs (i...
November 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27909729/self-renewal-molecular-mechanisms-of-colorectal-cancer-stem-cells
#15
Tianhui Pan, Jinghong Xu, Yongliang Zhu
Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal...
November 30, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27909410/mechanosensitive-molecular-networks-involved-in-transducing-resistance-exercise-signals-into-muscle-protein-accretion
#16
REVIEW
Emil Rindom, Kristian Vissing
Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise and/or the adequacy of low load resistance exercise regimens as well as underlying mechanisms. In this regard, delineation of the potentially mechanosensitive molecular mechanisms underlying muscle protein synthesis (MPS), may contribute to an understanding on how differentiated resistance exercise can transduce a mechanical signal into stimulation of muscle accretion...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27909050/notch-pathway-is-activated-via-genetic-and-epigenetic-alterations-and-is-a-therapeutic-target-in-clear-cell-renal-cancer
#17
Tushar D Bhagat, Yiyu Zou, Shizeng Huang, Jihwan Park, Matthew B Palmer, Caroline Hu, Wejuan Li, Niraj Shenoy, Orsolya Giricz, Gaurav Choudhary, Yiting Yu, Yi-An Ko, Maria C Izquierdo, Ae Seo Deok Park, Nishanth Vallumsetla, Remi Laurence, Robert Lopez, Masako Suzuki, James Pullman, Justin Kaner, Benjamin Gartrell, A Ari Hakimi, John M Greally, Bharvin Patel, Karim Benhadji, Kith Pradhan, Amit Verma, Katalin Susztak
Clear cell renal cell carcinoma (CCRCC) is an incurable malignancy in advanced stages and needs newer therapeutic targets. Transcriptomic analysis of CCRCCs and matched microdissected renal tubular controls revealed overexpression of NOTCH ligands and receptors in tumor tissues. Examination of the TCGA RNA-seq dataset also revealed widespread activation of NOTCH pathway in a large cohort of CCRCC samples. Samples with NOTCH pathway activation were also clinically distinct and were associated with better overall survival...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27908834/gamma-secretase-inhibitor-impairs-epithelial-to-mesenchymal-transition-induced-by-tgf-%C3%AE-in-ovarian-tumor-cell-lines
#18
M C Pazos, D Abramovich, A Bechis, P Accialini, F Parborell, M Tesone, G Irusta
Ovarian cancer is characterized by being highly metastatic, a feature that represents the main cause of failure of the treatment. This study investigated the effects of γ-secretase inhibition on the TGF-β-induced epithelial-mesenchymal transition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated in the presence of TGF-β showed morphological and biochemical changes related to EMT, which were blocked by co-stimulation with TGF-β and the γ-secretase inhibitor DAPT. In SKOV3 and IGROV1 cells, the co-stimulation blocked the cadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zeb1 induced by TGF-β...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27906684/phase-i-study-of-the-gamma-secretase-inhibitor-pf-03084014-in-combination-with-docetaxel-in-patients-with-advanced-triple-negative-breast-cancer
#19
Marzia A Locatelli, Philippe Aftimos, E Claire Dees, Patricia M LoRusso, Mark D Pegram, Ahmad Awada, Bo Huang, Rossano Cesari, Yuqiu Jiang, M Naveed Shaik, Kenneth A Kern, Giuseppe Curigliano
BACKGROUND: The NOTCH signaling pathway may be involved in the survival of stem cell-like tumor-initiating cells and contribute to tumor growth. In this phase Ib, open-label, multicenter study (NCT01876251), we evaluated PF-03084014, a selective gamma-secretase inhibitor in patients with advanced triple-negative breast cancer. METHODS: The dose-finding part was based on a 2×3 matrix design using the modified toxicity probability interval method. Oral PF-03084014 was administered twice daily continuously in combination with intravenous docetaxel given on day 1 of each 21-day cycle...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27904763/microrna-133a-3p-exerts-inhibitory-effects-on-gallbladder-carcinoma-via-targeting-rbpj
#20
Yuan Huang, Yaoshi Wu, Jiahong Dong, Dongdong Han, Shiwei Yang, Lin Jiang
Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with high mortality. The median survival time is 6 months, and the 5-year survival rate less than 5% for GBC patients. Thus, it is imperative to investigate the molecular mechanisms underlying the pathogenesis of GBC. miR-133a may exert anti-tumor effects on a variety of cancers. However, the role of miR-133a in the pathogenesis of GBC remains unclear. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) showed the miR-133a-3p expression markedly decreased in GBC as compared to adjacent normal tissues...
2016: American Journal of Cancer Research
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