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https://www.readbyqxmd.com/read/27913625/absence-of-mir-146a-in-podocytes-increases-risk-of-diabetic-glomerulopathy-via-upregulation-of-erbb4-and-notch-1
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/27904680/enhancement-of-early-cardiac-differentiation-of-dedifferentiated-fat-cells-by-dimethyloxalylglycine-via-notch-signaling-pathway
#11
Fuhai Li, Zongzhuang Li, Zhi Jiang, Ye Tian, Zhi Wang, Wei Yi, Chenyun Zhang
Background: Hypoxia has been reported to possess the ability to induce mature lipid-filled adipocytes to differentiate into fibroblast-like multipotent dedifferentiated fat (DFAT) cells and stem cells such as iPSCs (interstitial pluripotent stem cells) and ESCs (embryonic stem cells) and then to differentiate into cardiomyocytes. However, the effect of hypoxia on cardiac differentiation of DFAT cells and its underlying molecular mechanism remains to be investigated. Objective: To investigate the role of hypoxia in early cardiac differentiation of DFAT cells and the underlying molecular mechanism...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27902974/na-h-exchanger-1-has-tumor-suppressive-activity-and-prognostic-value-in-esophageal-squamous-cell-carcinoma
#12
Yosuke Ariyoshi, Atsushi Shiozaki, Daisuke Ichikawa, Hiroki Shimizu, Toshiyuki Kosuga, Hirotaka Konishi, Shuhei Komatsu, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Yoshinori Marunaka, Eigo Otsuji
Na+/H+ exchanger 1 (NHE1) is a plasma membrane transporter that controls intracellular pH and regulates apoptosis and invasion in various cancer cells. However, the function of NHE1 in esophageal squamous cell carcinoma (ESCC) cells and the relationship between the expression of NHE1 and prognosis of ESCC remain unclear. We found that the knockdown of NHE1 in ESCC cells inhibited apoptosis and promoted cell proliferation, migration, and invasion and showed increases in Snail, β-catenin, and activation of PI3K-AKT signaling, which was consistent with the results obtained from microarrays...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901093/macrophage-dependent-tumor-cell-transendothelial-migration-is-mediated-by-notch1-mena-inv-initiated-invadopodium-formation
#13
Jeanine Pignatelli, Jose Javier Bravo-Cordero, Minna Roh-Johnson, Saumil J Gandhi, Yarong Wang, Xiaoming Chen, Robert J Eddy, Alice Xue, Robert H Singer, Louis Hodgson, Maja H Oktay, John S Condeelis
The process of intravasation involving transendothelial migration is a key step in metastatic spread. How the triple cell complex composed of a macrophage, Mena over-expressing tumor cell and endothelial cell, called the tumor microenvironment of metastasis (TMEM), facilitates tumor cell transendothelial migration is not completely understood. Previous work has shown that the physical contact between a macrophage and tumor cell results in the formation of invadopodia, actin-rich matrix degrading protrusions, important for tumor cell invasion and transendothelial migration and tumor cell dissemination...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27901073/thd-module-extractor-an-application-for-cen-module-extraction-and-interesting-gene-identification-for-alzheimer-s-disease
#14
Tulika Kakati, Hirak Kashyap, Dhruba K Bhattacharyya
There exist many tools and methods for construction of co-expression network from gene expression data and for extraction of densely connected gene modules. In this paper, a method is introduced to construct co-expression network and to extract co-expressed modules having high biological significance. The proposed method has been validated on several well known microarray datasets extracted from a diverse set of species, using statistical measures, such as p and q values. The modules obtained in these studies are found to be biologically significant based on Gene Ontology enrichment analysis, pathway analysis, and KEGG enrichment analysis...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900706/anatomical-variations-of-the-trochlear-notch-angle-mri-analysis-of-78-elbows
#15
G Giannicola, M Scacchi, P Sedati, S Gumina
BACKGROUND: Little is known about the anatomical variations of the trochlear notch angle, nor do we know whether the cartilaginous layer modifies the trochlear bony contour. Our aim was to assess the variability of the bony and cartilaginous trochlear notch angles. MATERIALS AND METHODS: We assessed 78 healthy elbows (39 patients, 19 females and 20 males) with a mean age of 28 years (range 21-32). High-definition MRI coronal scans at the level of the flexion-extension axis were performed...
December 2016: Musculoskeletal Surgery
https://www.readbyqxmd.com/read/27900677/downregulation-of-the-long-non-coding-rna-meg3-promotes-angiogenesis-after-ischemic-brain-injury-by-activating-notch-signaling
#16
Juan Liu, Qing Li, Kun-Shan Zhang, Bin Hu, Xin Niu, Shu-Min Zhou, Si-Guang Li, Yu-Ping Luo, Yang Wang, Zhi-Feng Deng
Angiogenesis after ischemic brain injury contributes to the restoration of blood supply in the ischemic zone. Strategies to improve angiogenesis may facilitate the function recovery after stroke. Recent researches have demonstrated that dysfunction of long non-coding RNAs are associated with angiogenesis. We have previously reported that long non-coding RNAs (lncRNAs) are aberrantly expressed in ischemic stroke. However, little is known about long non-coding RNAs and theirs role in angiogenesis after stroke...
November 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27900345/new-insight-into-lsd1-function-in-human-cortical-neurogenesis
#17
Kazumi Hirano, Masakazu Namihira
The cerebral cortex of primates has evolved massively and intricately in comparison to that of other species. Accumulating evidence indicates that this is caused by changes in cell biological features of neural stem cells (NSCs), which differentiate into neurons and glial cells during development. The fate of NSCs during rodent cortical development is stringently regulated by epigenetic factors, such as histone modification enzymes, but the role of these factors in human corticogenesis is largely unknown. We have recently discovered that a lysine-specific demethylase 1 (LSD1), which catalyzes the demethylation of methyl groups in the histone tail, plays a unique role in human fetal NSCs (hfNSCs)...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27900295/diagnostic-performance-of-volume-and-limited-oblique-mri-of-the-anterior-cruciate-ligament-compared-to-knee-arthroscopy
#18
Paula J Richards, Iain McCall, Alexandra Kraus, Mary Jones, Gayle Maffulli, Stephen Bridgman, Nicola Maffulli
BACKGROUND: Many strategies have been used to improve the visualisation of the ACL including sagittal, coronal oblique sequences, and 3D volume imaging. Nevertheless, the ACL may not always be visualised. METHODS: Two hundred and thirty-one consecutive patients (77 females; 154 males; average age 43.5, range 18 to 82 years; 205 with chronic, 20 acute, and 6 acute on chronic symptoms) underwent knee arthroscopy for mechanical symptoms within a week of MRI. After routine orthogonal sequences, if general MRI radiographers, with over four years experience, were not able to identify the presence of the ACL, then two 3D volume sequences and 2D limited sagittal oblique T1 sequences were performed...
April 2016: Muscles, Ligaments and Tendons Journal
https://www.readbyqxmd.com/read/27900271/prosthetic-design-of-reverse-shoulder-arthroplasty-contributes-to-scapular-notching-and-instability
#19
Gazi Huri, Filippo Familiari, Nima Salari, Steve A Petersen, Mahmut Nedim Doral, Edward G McFarland
AIM: To evaluate whether implant design, glenoid positioning, and other factors influenced instability and scapular notching in reverse total shoulder arthroplasty. METHODS: We retrospectively reviewed records of patients who had undergone reverse total shoulder arthroplasty by the senior author from July 2004 through October 2011 and who had at least 24 mo of follow-up. The 58 patients who met the criteria had 65 arthroplasties: 18 with a Grammont-type prosthesis (Grammont group) and 47 with a lateral-based prosthesis (lateral-design group)...
November 18, 2016: World Journal of Orthopedics
https://www.readbyqxmd.com/read/27900056/inhibition-of-cell-proliferation-and-tumor-growth-of-colorectal-cancer-by-inhibitors-of-wnt-and-notch-signaling-pathways
#20
Yuliang Xiao, Xiaojing Yang, Yinglei Miao, Xikun He, Ming Wang, Weihong Sha
Understanding the role and mechanism of signaling pathways including Notch and Wnt in colorectal carcinogenesis is critical to the development of novel therapeutics. In the present study, we analyzed the cell proliferation, migration, G2/M percentage and the expression of molecules of signaling pathways in HCT-116 cells through the inhibition of Wnt and Notch pathways, and also investigated the effect of inhibitors of Wnt and Notch pathways on tumor growth in a transplantation tumor model. We observed that rDDK-1 (an inhibitor of the Wnt signaling pathway) and LY374973 (an inhibitor of the Notch signaling pathway) synergistically inhibited the proliferation, migration and G2/M percentage of HCT-116 cell lines, and could further synergistically inhibit the tumor volume and weight in the transplantation tumor model...
November 2016: Oncology Letters
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