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https://www.readbyqxmd.com/read/29142904/kras-g12d-upregulates-notch-signaling-to-induce-gallbladder-tumorigenesis-in-mice
#1
Wen-Cheng Chung, Junqing Wang, Yunyun Zhou, Keli Xu
Background: Kras mutations and increased Notch activation occur frequently in gallbladder cancer. However, their roles in gallbladder carcinogenesis have not been defined. This study was aimed at determining whether expression of mutant Kras was sufficient to induce gallbladder carcinoma and whether Notch deregulation played a role in this context. Methods: We determined Cre recombination activity of Pdx1-Cre in the gallbladder using a reporter strain and examined gallbladder tumor development in the Kras(LSL- G12D/+);Pdx1-Cre mice...
September 2017: Oncoscience
https://www.readbyqxmd.com/read/29101237/human-notch4-is-a-key-target-of-runx1-in-megakaryocytic-differentiation
#2
Yueying Li, Chen Jin, Hao Bai, Yongxing Gao, Shu Sun, Lei Chen, Lei Qin, Paul P Liu, Linzhao Cheng, Qian-Fei Wang
Megakaryocytes (MKs) in adult marrow produce platelets that play important roles in blood coagulation and hemostasis. Monoallelic mutations of the master transcription factor gene RUNX1 lead to familial platelet disorder (FPD) characterized by defective MK and platelet development. However, the molecular mechanisms of FPD remain unclear. Previously, we generated human induced pluripotent stem cells (iPSCs) from patients with FPD containing a RUNX1 nonsense mutation. Production of MKs from the FPD-iPSCs was reduced, and targeted correction of the RUNX1 mutation restored MK production...
November 3, 2017: Blood
https://www.readbyqxmd.com/read/29069725/notch4-and-mhc-class-ii-polymorphisms-are-associated-with-hcv-related-benign-and-malignant-lymphoproliferative-diseases
#3
Laura Gragnani, Elisa Fognani, Valli De Re, Massimo Libra, Adriana Garozzo, Patrizio Caini, Guia Cerretelli, Andrea Giovannelli, Serena Lorini, Monica Monti, Silvia Bagnoli, Irene Piaceri, Anna Linda Zignego
Mixed cryoglobulinemia (MC), is a HCV-related, clinically benign, lymphoproliferative disorder (LPD) that may evolve into a non Hodgkin's lymphoma (NHL). Significant associations were found between two single nucleotide polymorphisms near NOTCH4 (rs2071286) and the HLA class II (rs9461776) genes and HCV-related MC syndrome (MCS). We analyzed NOTCH4 rs2071286 and HLA-II rs9461776 in 3 HCV-related LPD groups (asymptomatic MC, MCS, NHL) with HCV infection without lymphoproliferative disorders. We found a positive relationship between NOTCH4 rs207186 T minor allele frequency (MAF) and patients with HCV-related LPDs at risk of NHL (Chi-square test for trend = 14...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29058285/notch4-inhibition-suppresses-invasion-and-vasculogenic-mimicry-formation-of-hepatocellular-carcinoma-cells
#4
Rui Cheng, Xin-Ran Cai, Kun Ke, Yan-Ling Chen
Vasculogenic mimicry (VM) is a process by which aggressive tumor cells generate non-endothelial cell-lined channels in malignant tumors including hepatocellular carcinoma (HCC). It has provided new insights into tumor behavior and has surfaced as a potential target for drug therapy. The molecular events underlying the process of VM formation are still poorly understood. In this study, we attempted to elucidate the relationship between Notch4 and VM formation in HCC. An effective siRNA lentiviral vector targeting Notch4 was constructed and transfected into Bel7402, a HCC cell line...
October 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/29054964/gene-expression-profiling-of-the-notch-ahr-il22-axis-at-homeostasis-and-in-response-to-tissue-injury
#5
Marc Weidenbusch, Severin Rodler, Shangqing Song, Simone Romoli, Julian A Marschner, Franziska Kraft, Alexander Holderied, Santosh Kumar, Shrikant R Mulay, Mohsen Honarpisheh, Satish Kumar Devarapu, Maciej Lech, Hans-Joachim Anders
Notch and Interleukin-22 signaling are known to regulate tissue homeostasis and response to injury in humans and mice, and the induction of endogenous arylhydrocarbon receptor ligands through Notch links the two pathways in a hierarchical fashion. However, in adults the species-, organ- and injury-specific gene expression of the Notch-AhR-IL22 axis components is unknown. We therefore performed gene expression profiling of DLL1, DLL3, DLL4, DLK1, DLK2, JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, ADAM17/TACE, PSEN1, BSG/CD147, RBP-J, HES1, HES5, HEY1, HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL22, IL22RA1, IL22RA2, IL10RB, and STAT3 under homeostatic conditions in 10 mature murine and human organs...
October 20, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29052507/metabolic-shift-in-density-dependent-stem-cell-differentiation
#6
Simar J Singh, William Turner, Drew E Glaser, Kara E McCloskey, Fabian V Filipp
BACKGROUND: Vascular progenitor cells (VPCs) derived from embryonic stem cells (ESCs) are a valuable source for cell- and tissue-based therapeutic strategies. During the optimization of endothelial cell (EC) inductions from mouse ESCs using our staged and chemically-defined induction methods, we found that cell seeding density but not VEGF treatment between 10 ng/mL and 40 ng/mL was a significant variable directing ESCs into FLK1(+) VPCs during stage 1 induction. Here, we examine potential contributions from cell-to-cell signaling or cellular metabolism in the production of VPCs from ESCs seeded at different cell densities...
October 20, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29042932/cardioprotective-effect-of-notch-signaling-on-the-development-of-myocardial-infarction-complicated-by-diabetes-mellitus
#7
Fang Wu, Bo Yu, Xu Zhang, Yuelan Zhang
The present study aimed to elucidate the role of Notch signaling in the development of myocardial infarction (MI) concomitant with diabetes in vivo and in vitro and evaluated the therapeutic effect of the Notch signaling in vitro. Streptozotocin-induced diabetic rats were subjected to 25 min of ischemia and 2 h of reperfusion. Cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) isoenzyme levels were detected. Infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining. Myocardial apoptosis and fibrosis were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Masson Trichrome staining, respectively...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29036275/porcupine-dependent-wnt-activity-within-the-uterine-epithelium-is-essential-for-fertility
#8
Omar Farah, Steffen Biechele, Janet Rossant, Daniel Dufort
The secretion of mammalian Wnt ligands within the cell is dependent on the activity of Porcupine, a gene located on the X-chromosome that encodes for a membrane bound o-acyl transferase. Here, we report that post-natal ablation of Porcupine in the uterine luminal epithelium alone results in the decrease in endometrial gland number. Despite having uterine glands, mutant females are completely infertile. Epithelial ablation of Porcupine causes defects in timely apposition of the lumen, along with failure to respond to artificial decidual induction...
October 4, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28871079/sirt6-deficiency-exacerbates-podocyte-injury-and-proteinuria-through-targeting-notch-signaling
#9
Min Liu, Kaili Liang, Junhui Zhen, Meng Zhou, Xiaojie Wang, Ziying Wang, Xinbing Wei, Yan Zhang, Yu Sun, Zhuanli Zhou, Hua Su, Chun Zhang, Ningjun Li, Chengjiang Gao, Jun Peng, Fan Yi
Podocyte injury is a major determinant of proteinuric kidney disease and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. Sirt6 is downregulated in renal biopsies from patients with podocytopathies and its expression correlates with glomerular filtration rate. Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models, diabetic nephropathy, and adriamycin-induced nephropathy...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28862627/analysis-of-the-microvascular-morphology-and-hemodynamics-of-breast-cancer-in-mice-using-spring-8-synchrotron-radiation-microangiography
#10
Masae Torii, Toshifumi Fukui, Masashi Inoue, Shotaro Kanao, Keiji Umetani, Mikiyasu Shirai, Tadakatsu Inagaki, Hirotsugu Tsuchimochi, James T Pearson, Masakazu Toi
Tumor vasculature is characterized by morphological and functional abnormalities. However, analysis of the dynamics in blood flow is still challenging because of limited spatial and temporal resolution. Synchrotron radiation (SR) microangiography above the K-edge of the iodine contrast agent can provide high-contrast imaging of microvessels in time orders of milliseconds. In this study, mice bearing the human breast cancer cell lines MDAMB231 and NOTCH4 overexpression in MDAMB231 (MDAMB231(NOTCH4+)) and normal mice were assessed using SR microangiography...
September 1, 2017: Journal of Synchrotron Radiation
https://www.readbyqxmd.com/read/28676722/the-role-of-the-notch-signal-pathway-in-mucosal-cell-metaplasia-in-mouse-acute-otitis-media
#11
Xiang Liu, Ning Cong, Xiang Cheng, Rui Ma, Jing Wang, Yi-Bo Huang, Meng Zhao, Xin-Wei Wang, Fang-Lu Chi, Dong-Dong Ren
Otitis media (OM) is a major cause of morbidity in pediatric and adult patients. This inflammatory condition is characterized by mucous cell hyperplasia that is thought to produce mucins from the middle ear mucosa. We are interested in the role of Notch signalling pathway in this inflammatory process. Using an acute otitis media (AOM) mouse model through injection of Streptococcus Pneumoniae into the middle ear, histopathologic examination and quantitative RT-PCR, acute inflammation with the thickness of mucosa, Goblet cell hyperplasia, and cilia loss were determined and gene expression related to the Notch signaling pathway were evaluated...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28624953/genome-wide-analysis-of-differential-dna-methylation-in-silver-russell-syndrome
#12
Di Wu, Chunxiu Gong, Chang Su
Silver-Russell Syndrome (SRS) is clinically heterogeneous disorder characterized by low birth weight, postnatal growth restriction, and variable dysmorphic features. Current evidence strongly implicates imprinted genes as an important etiology of SRS. Although almost half of the patients showed DNA hypomethylation at the H19/IGF2 imprinted domain, and approximately 7%-10% of SRS patients have maternal uniparental disomy of chromosome 7 (UPD (7) mat); the rest of the SRS patients shows unknown etiology. In this study, we investigate whether there are further DNA methylation defects in SRS patients...
July 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28623973/dynamic-maternal-and-fetal-notch-activity-and-expression-in-placentation
#13
Heather I Levin, Chantae S Sullivan-Pyke, Virginia E Papaioannou, Ronald J Wapner, Jan K Kitajewski, Carrie J Shawber, Nataki C Douglas
INTRODUCTION: Murine placentation requires trophoblast Notch2, while the Notch ligand, JAGGED1, is reduced in invasive trophoblasts from women with preeclampsia. However, the placental cells with active Notch signaling and expression of other Notch proteins and ligands in placentation have yet to be defined. We sought to identify endothelial cell and trophoblast subtypes with canonical Notch signaling in the decidua and placenta and correlate this to expression of Notch proteins and ligands...
July 2017: Placenta
https://www.readbyqxmd.com/read/28617548/bioinformatic-analysis-of-prognostic-value-of-arap3-in-breast-cancer-and-the-associated-signaling-pathways
#14
J-J Han, B-R Du, C-H Zhang
OBJECTIVE: In this study, we tried to pool previous annotated genomic data to assess the association between ARAP3 expression and metastatic relapse (MR) risk in patients with breast cancer. Moreover, we also investigated the signaling pathways in which ARAP3 might be involved in breast cancer. MATERIALS AND METHODS: The raw microarray data (GDS5666) that compared gene transcriptional profiles of 4T1 derived lung-aggressive explant and primary tumor explant were reanalyzed to identify the dysregulated genes...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28587423/notch4-signaling-pathway-in-a-kawasaki-disease-mouse-model-induced-by-lactobacillus-casei-cell-wall-extract
#15
Lichao Gao, Songling Fu, Wei Wang, Chunhong Xie, Yiying Zhang, Fangqi Gong
The present study aimed to explore the role of the Notch4 signaling pathway in a mouse model of Kawasaki disease (KD) induced by Lactobacillus casei cell wall extract (LCWE). BALB/c male mice (4-6 weeks old) were intraperitoneally injected with 500 µg LCWE in phosphate-buffered saline (PBS) or PBS alone (control group). At days 3, 7, 14 and 28, the numbers of circulating endothelial progenitor cells (EPCs) in the peripheral blood and the expression of Notch4 on the surface of EPCs were detected. In addition, the levels of vascular cell adhesion molecule 1 (VCAM-1) and P-selectin in the roots of coronary arteries were evaluated...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28568708/prognostic-value-of-notch-receptors-in-postsurgical-patients-with-hepatitis-b-virus-related-hepatocellular-carcinoma
#16
Tingdong Yu, Chuangye Han, Guangzhi Zhu, Xiwen Liao, Wei Qin, Chengkun Yang, Zhen Liu, Hao Su, Xiaoguang Liu, Long Yu, Zhengtao Liu, Sicong Lu, Zhiwei Chen, Yu Liang, Jianlu Huang, Xue Qin, Ying Gui, Jiaquan Li, Tao Peng
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and a major cause of cancer involved death worldwide. Prognosis remains poor because of high recurrence rates and lack of effective relapse prevention strategies. Notch pathway plays an important role in tumor progression and metastasis, and it is associated with the prognosis of cancer. A total of 465 hepatitis B virus (HBV)-related HCC patients who underwent surgery were enrolled. Single nucleotide polymorphisms (SNP) of Notch pathway receptors were genotyped using Sanger DNA sequencing...
July 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28560257/generating-testable-hypotheses-for-schizophrenia-and-rheumatoid-arthritis-pathogenesis-by-integrating-epidemiological-genomic-and-protein-interaction-data
#17
Tulsi A Malavia, Srilakshmi Chaparala, Joel Wood, Kodavali Chowdari, Konasale M Prasad, Lora McClain, Anil G Jegga, Madhavi K Ganapathiraju, Vishwajit L Nimgaonkar
Patients with schizophrenia and their relatives have reduced prevalence of rheumatoid arthritis. Schizophrenia and rheumatoid arthritis genome-wide association studies also indicate negative genetic correlations, suggesting that there may be shared pathogenesis at the DNA level or downstream. A portion of the inverse prevalence could be attributed to pleiotropy, i.e., variants of a single nucleotide polymorphism that could confer differential risk for these disorders. To study the basis for such an interrelationship, we initially compared lists of single nucleotide polymorphisms with significant genetic associations (p < 1(e-8)) for schizophrenia or rheumatoid arthritis, evaluating patterns of linkage disequilibrium and apparent pleiotropic risk profiles...
2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28538208/notch4-and-mhc%C3%A2-class-ii-polymorphisms-are-associated-with%C3%A2-hcv-related-benign-and-malignant-lymphoproliferative-diseases
#18
Laura Gragnani, Elisa Fognani, Valli De Re, Massimo Libra, Adriana Garozzo, Patrizio Caini, Guia Cerretelli, Andrea Giovannelli, Serena Lorini, Monica Monti, Silvia Bagnoli, Irene Piaceri, Anna Linda Zignego
Mixed cryoglobulinemia (MC), is a HCV-related, clinically benign, lymphoproliferative disorder (LPD) that may evolve into a non Hodgkin's lymphoma (NHL). Significant associations were found between two single nucleotide polymorphisms near NOTCH4 (rs2071286) and the HLA class II (rs9461776) genes and HCV-related MC syndrome (MCS). We analyzed NOTCH4 rs2071286 and HLA-II rs9461776 in 3 HCV-related LPD groups (asymptomatic MC, MCS, NHL) with HCV infection without lymphoproliferative disorders.We found a positive relationship between NOTCH4 rs207186 T minor allele frequency (MAF) and patients with HCV-related LPDs at risk of NHL (Chi-square test for trend = 14...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28482141/notch-pathway-is-active-during-osteogenic-differentiation-of-human-bone-marrow-mesenchymal-stem-cells-induced-by-pulsed-electromagnetic-fields
#19
Leila Bagheri, Agnese Pellati, Paola Rizzo, Giorgio Aquila, Leo Massari, Monica De Mattei, Alessia Ongaro
Pulsed electromagnetic fields (PEMFs) have been used to treat bone diseases, particularly non-union healing. Although it is known that PEMFs promote the osteogenic differentiation of human mesenchymal stem cells (hMSCs), to date PEMF molecular mechanisms remain not clearly elucidated. The Notch signaling is a highly conserved pathway which regulates cell fate decisions and skeletal development. The aim of this study was to investigate if the known PEMF-induced osteogenic effects may involve the modulation of the Notch pathway...
May 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28415574/prognostic-roles-of-notch-receptor-mrna-expression-in-human-ovarian-cancer
#20
Chuan Chen, Xiaojiao Wang, Shunping Huang, Lin Wang, Lili Han, Songtao Yu
Aberrant activation of Notch signaling pathway has been correlated with high grade ovarian carcinoma and carcinogenesis. However, the predictive and prognostic values of Notch signaling pathway in ovarian cancer patients remains unclear. We utilize "The Kaplan-Meier plotter" (KM plotter) background database to access the prognostic values including overall survival (OS), progression-free survival (PFS), as well as post-progression survival (PPS) of four Notch receptor mRNA expression in ovarian cancer patients...
May 16, 2017: Oncotarget
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