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https://www.readbyqxmd.com/read/28932899/voluntary-running-enhanced-synaptic-plasticity-learning-and-memory-are-mediated-by-notch1-signal-pathway-in-c57bl-mice
#1
Xiaochen Zhang, Chunxiao Yang, Jing Gao, Hongqiang Yin, Hui Zhang, Tao Zhang, Zhuo Yang
It is well known that voluntary running can enhance synaptic plasticity and improve learning and memory abilities. The Notch1 receptor is also reported to be associated with these processes, but its role in running-induced alterations is unclear. In this study, we aimed to investigate whether the Notch1 signalling pathway was involved in voluntary running-induced enhancement of synaptic plasticity, learning and memory. Notch1 heterozygous deficient (Notch1(+/-)) mice and wildtype (WT) C57BL littermates were randomly divided into runner group and non-runner group...
September 20, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28931948/abnormal-arterial-venous-fusions-and-fate-specification-in-mouse-embryos-lacking-blood-flow
#2
Jennifer J Hwa, Nathan Beckouche, Lawrence Huang, Yoseph Kram, Henrik Lindskog, Rong A Wang
The functions of blood flow in the morphogenesis of mammalian arteries and veins are not well understood. We examined the development of the dorsal aorta (DA) and the cardinal vein (CV) in Ncx1 (-/-) mutants, which lack blood flow due to a deficiency in a sodium calcium ion exchanger expressed specifically in the heart. The mutant DA and CV were abnormally connected. The endothelium of the Ncx1 (-/-) mutant DA lacked normal expression of the arterial markers ephrin-B2 and Connexin-40. Notch1 activation, known to promote arterial specification, was decreased in mutant DA endothelial cells (ECs), which ectopically expressed the venous marker Coup-TFII...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931897/identification-and-characterization-of-a-novel-sso7d-scaffold-based-binder-against-notch1
#3
Tenzin Gocha, Balaji M Rao, Ramanuj DasGupta
Notch signaling has important functions in regulating cell growth and development, misregulation of which has been implicated in various cancers. Monoclonal antibodies (mAbs) targeting Notch protein activity have already moved into clinical trials. However due to the limitations associated with cost and productivity of mAbs, there has been a surge in the development of complementary approaches that are based on non-antibody scaffolds. Non-antibody scaffolds are small proteins that are stable and can be engineered to develop high-affinity binders against specific targets of interest...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28927121/the-role-of-jagged1-notch-pathway-mediated-angiogenesis-of-hepatocarcinoma-cells-in-vitro-and-the-effects-of-the-spleen-invigorating-and-blood-stasis-removing-recipe
#4
Juze Lin, Yongxin Lin, Le Su, Qiao Su, Wei Guo, Xuhui Huang, Changjun Wang, Lizhu Lin
The objective of this study was to observe the effect of Jagged1/Notch pathway-mediated angiogenesis on the in vitro proliferation of hepatocellular carcinoma cells, and the effect and possible mechanism of the spleen-invigorating and blood stasis-removing recipe. Spleen-invigorating and blood stasis-removing recipe serum from SPF grade nude mice was prepared, and the fingerprint of the drugs of the spleen-invigorating and blood stasis-removing recipe and drug serum were identified by HPLC. SMMC-7721 human hepatocellular carcinoma cells were divided into the normal control group, DAPT inhibitor control group, and drug serum group according to the different treatments...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925785/risk-adjusted-therapy-in-chronic-lymphocytic-leukemia-a-phase-ii-cancer-trials-ireland-ctrial-ie-icorg-07-01-study-of-fludarabine-cyclophosphamide-and-rituximab-therapy-evaluating-response-adapted-abbreviated-frontline-therapy-with-fcr-in-non-del-17p-cll
#5
Niamh Appleby, David O'Brien, Fiona M Quinn, Liam Smyth, Johanna Kelly, Imelda Parker, Kathleen Scott, Mary R Cahill, Gerard Crotty, Helen Enright, Brian Hennessy, Andrew Hodgson, Maeve Leahy, Hilary O'Leary, Michael O'Dwyer, Amjad Hayat, Elisabeth A Vandenberghe
Minimal residual disease negative complete response (MRD-negative CR) provides an early marker for time to treatment failure (TTF) in CLL treated with fludarabine, cyclophosphamide, and rituximab (FCR). MRD was assessed after four FCR cycles (FCR4); MRD-negative CR patients discontinued treatment. Fifty-two patients (35M; 17F) were enrolled. Eighteen (18/52; 34.6%) patients reached MRD-negative CR after FCR4 and 29/52 (55.8%) were MRD-negative CR at end of treatment (EOT). Median TTF was 71.1 months (95% CI 61...
September 19, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28924218/uncontrolled-angiogenic-precursor-expansion-causes-coronary-artery-anomalies-in-mice-lacking-pofut1
#6
Yidong Wang, Bingruo Wu, Pengfei Lu, Donghong Zhang, Brian Wu, Shweta Varshney, Gonzalo Del Monte-Nieto, Zhenwu Zhuang, Rabab Charafeddine, Adam H Kramer, Nicolas E Sibinga, Nikolaos G Frangogiannis, Richard N Kitsis, Ralf H Adams, Kari Alitalo, David J Sharp, Richard P Harvey, Pamela Stanley, Bin Zhou
Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure...
September 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28923385/targeting-breast-cancer-stem-cells-by-novel-hdac3-selective-inhibitors
#7
Hao-Yu Hsieh, Hsiao-Ching Chuang, Fang-Hsiu Shen, Kinjal Detroja, Ling-Wei Hsin, Ching-Shih Chen
Although histone deacetylase (HDAC) inhibitors have been known to suppress the cancer stem cell (CSC) population in multiple types of cancer cells, it remains unclear which HDAC isoforms and corresponding mechanisms contribute to this anti-CSC activity. Pursuant to our previous finding that HDAC8 regulates CSCs in triple-negative breast cancer (TNBC) cells by targeting Notch1 stability, we investigated related pathways and found HDAC3 to be mechanistically linked to CSC homeostasis by increasing β-catenin expression through the Akt/GSK3β pathway...
September 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28923203/epigenetic-silencing-of-mirna-34a-in-human-cholangiocarcinoma-via-ezh2-and-dna-methylation-impact-on-regulation-of-notch-pathway
#8
Hyunjoo Kwon, Kyoungsub Song, Chang Han, Jinqiang Zhang, Lu Lu, Weina Chen, Tong Wu
Aberrant expression and regulation of miRNAs have been implicated in multiple stages of tumorigenic processes. The current study was designed to explore the biological function and epigenetic regulation of miR-34a in human cholangiocarcinoma (CCA). Our data show that the expression of miR-34a is decreased significantly in CCA cells compared with non-neoplastic biliary epithelial cells. Forced overexpression of miR-34a in CCA cells inhibited their proliferation and clonogenic capacity in vitro, and suppressed tumor xenograft growth in severe combined immunodeficiency mice...
October 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28920078/notch1-activation-depletes-the-pool-of-side-population-stem-cells-in-atl
#9
Xue Tao Bai, Chien-Hung Yeh, Christophe Nicot
BACKGROUND: HTLV-I infection is associated with the development of adult T-cell leukemia (ATL), a malignancy characterized by a high rate of disease relapse and poor survival. Previous studies reported the existence of side population (SP) cells in HTLV-I Tax transgenic mouse models. These studies showed that these ATL-like derived SP cells have both self-renewal and leukemia renewal capacity and represent Cancer Stem Cells (CSC)/Leukemia-Initiating Cells (LIC). Since CSC/LIC are resistant to conventional therapies, a better characterization is needed...
June 2017: Journal of Cancer Sciences
https://www.readbyqxmd.com/read/28916710/apc-sets-the-wnt-tone-necessary-for-cerebral-cortical-progenitor-development
#10
Naoki Nakagawa, Jingjun Li, Keiko Yabuno-Nakagawa, Tae-Yeon Eom, Martis Cowles, Tavien Mapp, Robin Taylor, E S Anton
Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex...
September 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28915655/notch-system-is-differentially-expressed-and-activated-in-pituitary-adenomas-of-distinct-histotype-tumor-cell-lines-and-normal-pituitaries
#11
Sofia Perrone, Lautaro Zubeldia-Brenner, Elias Gazza, Gianina Demarchi, Leticia Baccarini, Agustin Baricalla, Freya Mertens, Guillermina Luque, Hugo Vankelecom, Silvia Berner, Damasia Becu-Villalobos, Carolina Cristina
Pituitary adenomas are among the most frequent intracranial neoplasms and treatment depends on tumor subtype and clinical features. Unfortunately, non responder cases occur, then new molecular targets are needed. Notch system component expression and activation data are scarce in pituitary tumorigenesis, we therefore aimed to characterize Notch system in pituitary tumors of different histotype. In human pituitary adenomas we showed NOTCH1-4 receptors, JAGGED1 ligand and HES1 target gene expression with positive correlations between NOTCH1,2,4 and HES1, and NOTCH3 and JAGGED1 denoting Notch system activation in a subset of tumors...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914715/diffuse-staining-for-activated-notch1-correlates-with-notch1-mutation-status-and-is-associated-with-worse-outcome-in-adenoid-cystic-carcinoma
#12
Dipti P Sajed, William C Faquin, Chris Carey, Eric A Severson, Amir H Afrogheh, Carl A Johnson, Stephen C Blacklow, Nicole G Chau, Derrick T Lin, Jeffrey F Krane, Vickie Y Jo, Joaquín J Garcia, Lynette M Sholl, Jon C Aster
NOTCH1 is frequently mutated in adenoid cystic carcinoma (ACC). To test the idea that immunohistochemical (IHC) staining can identify ACCs with NOTCH1 mutations, we performed IHC for activated NOTCH1 (NICD1) in 197 cases diagnosed as ACC from 173 patients. NICD1 staining was positive in 194 cases (98%) in 2 major patterns: subset positivity, which correlated with tubular/cribriform histology; and diffuse positivity, which correlated with a solid histology. To determine the relationship between NICD1 staining and NOTCH1 mutational status, targeted exome sequencing data were obtained on 14 diffusely NICD1-positive ACC specimens from 11 patients and 15 subset NICD1-positive ACC specimens from 15 patients...
September 13, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28914259/epigenetic-targeting-of-notch1-driven-transcription-using-the-hdaci-panobinostat-is-a-potential-therapy-against-t-cell-acute-lymphoblastic-leukemia
#13
M Waibel, S J Vervoort, I Y Kong, S Heinzel, K M Ramsbottom, B P Martin, E D Hawkins, R W Johnstone
Leukemia accepted article preview online, 15 September 2017. doi:10.1038/leu.2017.282.
September 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28913955/controlled-jagged1-delivery-induces-human-embryonic-palate-mesenchymal-cells-to-form-osteoblasts
#14
Jean De La Croix Ndong, Stephenson Yvonne, Michael E Davis, Andrés J García, Steven Goudy
Osteoblast commitment and differentiation are controlled by multiple growth factors including members of the Notch signaling pathway. JAGGED1 is a cell surface ligand of the Notch pathway that is necessary for murine bone formation. The delivery of JAGGED1 to induce bone formation is complicated by its need to be presented in a bound form to allow for proper Notch receptor signaling. In this study we investigate whether the sustained release of JAGGED1 stimulates human mesenchymal cells to commit to osteoblast cell fate using polyethylene glycol malemeide (PEG-MAL) hydrogel delivery system...
September 15, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28910158/interaction-between-rare-variants-in-notch1-and-betel-quid-chewing-in-oral-squamous-cell-carcinoma
#15
Chia-Min Chung, Chien-Hung Lee, Mu-Kuan Chen, Ming-Hsui Tsai, Ying-Chin Ko
BACKGROUND: In this study, we investigated rare variants of the NOTCH1 gene located near somatic mutations as surrogate markers, as well as the relationship of these rare variants with betel quid (BQ) chewing and the occurrence of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: A total of 410 patients diagnosed with OSCC and 282 unrelated, healthy subjects without cancer were recruited from two medical centers in Taiwan. Odds ratios (OR) and 95% confidence intervals (CI) were assessed by logistic regression...
September 14, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28905115/clinical-application-of-snp-array-analysis-in-fetuses-with-ventricular-septal-defects-and-normal-karyotypes
#16
Fang Fu, Qiong Deng, Ting-Ying Lei, Ru Li, Xiang-Yi Jing, Xin Yang, Can Liao
PURPOSE: The present study aims to evaluate the utility of high-resolution single-nucleotide polymorphism (SNP) arrays in fetuses with ventricular septal defects (VSDs) with or without other structural anomalies but with normal karyotypes and to investigate the outcomes of cases of prenatal VSDs via clinical follow-up. METHODS: We analyzed 144 fetuses with VSDs and normal karyotypes using Affymetrix CytoScan HD arrays and the analyses were carried out a year after birth...
September 13, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28904317/notch-signaling-partly-regulates-the-osteogenic-differentiation-of-retinoic-acid-treated-murine-induced-pluripotent-stem-cells
#17
Thanaphum Osathanon, Jeeranan Manokawinchoke, Hiroshi Egusa, Prasit Pavasant
Notch signaling is involved in osteogenic differentiation; however, its role differs depending on cell type and differentiation stage. Here, we investigated the involvement of Notch signaling in the osteogenic differentiation of retinoic acid-treated embryoid bodies derived from mouse gingival fibroblast-derived induced pluripotent stem cells (mGF-iPSCs). When cultured in osteogenic media, mGF-iPSCs showed an increase in their expression of osteogenic marker genes and deposited a mineralized matrix. Furthermore, increased levels of mRNA for Notch1, Notch2, and Hey1 were observed...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28903429/lenalidomide-restores-the-osteogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-from-multiple-myeloma-patients-via-deactivating-notch-signaling-pathway
#18
Juan Guo, Chengming Fei, Youshan Zhao, Sida Zhao, Qingqing Zheng, Jiying Su, Dong Wu, Xiao Li, Chunkang Chang
Multiple myeloma (MM) always presents osteolytic bone lesions, resulting from the abnormal osteoblastic and osteoclastic function in patients. MM patients exhibit the impairment of osteogenic differentiation of BMMSCs (bone marrow mesenchymal stem cells) and osteoblast deficiency. Effects of the drug, lenalidomide on the osteoblastic functions and the involved mechanisms remain unexplored. In the present study, it is observed that the osteogenic differentiation of BMMSCs from MM patients (MM-MSCs) is impaired and activation of Notch signaling pathway in MM-MSCs is abnormal...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901537/tetrandrine-antagonizes-acute-megakaryoblastic-leukemia-growth-by-forcing-autophagy-mediated-differentiation
#19
Ting Liu, Zhenxing Zhang, Chunjie Yu, Chang Zeng, Xiaoqing Xu, Guixian Wu, Zan Huang, Wenhua Li
BACKGROUND AND PURPOSE: The dismal prognosis of acute megakaryoblastic leukemia (AMKL) urges for development of novel therapeutic methods. Inducing megakaryoblasts to undergo terminal differentiation was recently shown to be effective as a treatment for AMKL. This encouraged us to identify a potent anti-leukemia compound to induce megakaryocyte differentiation. EXPERIMENTAL APPROACH: Expression of CD41 and morphology change were observed in AMKL cells after tetrandrine treatment...
September 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28901188/engineered-microvasculature-in-pdms-networks-using-endothelial-cells-derived-from-human-induced-pluripotent-stem-cells
#20
Amogh Sivarapatna, Mahboobe Ghaedi, Yang Xiao, Edward Han, Binod Aryal, Jing Zhou, Carlos Fernandez-Hernando, Yibing Qyang, Karen K Hirschi, Laura E Niklason
In this study, we used a polydimethylsiloxane (PDMS)-based platform for the generation of intact, perfusion-competent microvascular networks in vitro. COMSOL Multiphysics, a finite-element analysis and simulation software package, was used to obtain simulated velocity, pressure, and shear stress profiles. Transgene-free human induced pluripotent stem cells (hiPSCs) were differentiated into partially arterialized endothelial cells (hiPSC-ECs) in 5 d under completely chemically defined conditions, using the small molecule glycogen synthase kinase 3β inhibitor CHIR99021 and were thoroughly characterized for functionality and arterial-like marker expression...
August 2017: Cell Transplantation
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