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https://www.readbyqxmd.com/read/27932350/role-of-noncanonical-wnts-signaling-pathway-in-human-aortic-valve-calcification
#1
Isabella Albanese, Bin Yu, Hamood Al-Kindi, Bianca Barratt, Leah Ott, Mohammad Al-Refai, Benoit de Varennes, Dominique Shum-Tim, Marta Cerruti, Ophélie Gourgas, Eric Rhéaume, Jean-Claude Tardif, Adel Schwertani
OBJECTIVE: The mechanisms underlying the pathogenesis of aortic valve calcification remain unclear. With accumulating evidence demonstrating that valve calcification recapitulates bone development, the crucial roles of noncanonical Wnt ligands WNT5a, WNT5b, and WNT11 in osteogenesis make them critical targets in the study of aortic valve calcification. APPROACH AND RESULTS: Using immunohistochemistry, RT-PCR, Western blotting, and tissue culture, we examined the tissue distribution of WNT5a, WNT5b, and WNT11 in noncalcified and calcified aortic valves and their effects on human aortic valve interstitial cells (HAVICs)...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27932247/crystal-structure-of-the-pdz-domain-of-mouse-dishevelled-1-and-its-interaction-with-cxxc5
#2
Inhwan Lee, Sooho Choi, Ji-Hye Yun, Seolhwa Seo, Sehee Choi, Kang-Yell Choi, Weontae Lee
Dishevelled (Dvl) plays a crucial role in Wnt signaling by interacting with membrane-bound receptors and downstream molecules through its PDZ domain. CXXC5 is one of the key molecules that interacts with Dvl and negatively regulates the Wnt/β-catenin pathway in osteoblast differentiation. Recently, the Dvl-CXXC5 interaction has been identified as an excellent target for osteoporosis treatment. Therefore, it is desirable to have detailed structural information for the Dvl-CXXC5 interaction. Although solution structures of the Dvl1 PDZ domain have been reported, a high-resolution crystal structure would provide detailed sidechain information that is essential for drug development...
December 5, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27930333/tet-proteins-influence-the-balance-between-neuroectodermal-and-mesodermal-fate-choice-by-inhibiting-wnt-signaling
#3
Xiang Li, Xiaojing Yue, William A Pastor, Lizhu Lin, Romain Georges, Lukas Chavez, Sylvia M Evans, Anjana Rao
TET-family dioxygenases catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and oxidized methylcytosines in DNA. Here, we show that mouse embryonic stem cells (mESCs), either lacking Tet3 alone or with triple deficiency of Tet1/2/3, displayed impaired adoption of neural cell fate and concomitantly skewed toward cardiac mesodermal fate. Conversely, ectopic expression of Tet3 enhanced neural differentiation and limited cardiac mesoderm specification. Genome-wide analyses showed that Tet3 mediates cell-fate decisions by inhibiting Wnt signaling, partly through promoter demethylation and transcriptional activation of the Wnt inhibitor secreted frizzled-related protein 4 (Sfrp4)...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27930095/multi-omics-data-integration-and-mapping-of-altered-kinases-to-pathways-reveal-gonadotropin-hormone-signaling-in-glioblastoma
#4
Savita Jayaram, Manoj Kumar Gupta, Rajesh Raju, Poonam Gautam, Ravi Sirdeshmukh
Glioblastoma multiforme (GBM) is one of the most lethal brain tumors with an inadequately understood pathophysiology. Biomarkers that guide accurate diagnosis and treatment decisions would greatly support precision medicine for GBM. Previous studies of GBM have focused on signaling pathways such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptors (PDGFRs), notch, wnt, and others, identified with single omics technology platforms (genomics, transcriptomics, or proteomics), but not with their integrated use...
December 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27927684/in-vitro-patterning-of-pluripotent-stem-cell-derived-intestine-recapitulates-in-vivo-human-development
#5
Yu-Hwai Tsai, Roy Nattiv, Priya H Dedhia, Melinda S Nagy, Alana M Chin, Matthew Thomson, Ophir Klein, Jason Spence
The intestine plays a central role in digestion, nutrient absorption and metabolism, with individual regions of the intestine having distinct functional roles. For example, the most proximal region of the small intestine, the duodenum, is associated with absorption of micronutrients such as iron and folate, whereas the more distal ileum is responsible for recycling bile salts. Many examples of region-specific gene expression in the adult intestine are known, but how intestinal regional identity is established during development is a largely open question...
December 7, 2016: Development
https://www.readbyqxmd.com/read/27927230/molecular-control-of-nitric-oxide-synthesis-through-enos-and-caveolin-1-interaction-regulates-osteogenic-differentiation-of-adipose-derived-stem-cells-by-modulation-of-wnt-%C3%AE-catenin-signaling
#6
Nadeeka Bandara, Saliya Gurusinghe, Shiang Yong Lim, Haying Chen, Shuangfeng Chen, Dawei Wang, Bryan Hilbert, Le-Xin Wang, Padraig Strappe
BACKGROUND: Nitric oxide (NO) plays a role in a number of physiological processes including stem cell differentiation and osteogenesis. Endothelial nitric oxide synthase (eNOS), one of three NO-producing enzymes, is located in a close conformation with the caveolin-1 (CAV-1(WT)) membrane protein which is inhibitory to NO production. Modification of this interaction through mutation of the caveolin scaffold domain can increase NO release. In this study, we genetically modified equine adipose-derived stem cells (eASCs) with eNOS, CAV-1(WT), and a CAV-1(F92A) (CAV-1(WT) mutant) and assessed NO-mediated osteogenic differentiation and the relationship with the Wnt signaling pathway...
December 7, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27927069/efficient-differentiation-of-tbx18-wt1-epicardial-like-cells-from-human-pluripotent-stem-cells-using-small-molecular-compounds
#7
Yue Ma, Jianmin Zhao, Henghua Cao, Luyang Tian, Weibang Huo, Kui Zhai, Pei Wang, Guangju Ji
The epicardium promotes neovascularization and cardiomyocyte regeneration by generating vascular smooth muscle cells (SMCs) and producing regenerative factors after adult heart infarction. It is therefore a potential cell resource for repair of the injured heart. However, the epicardium also participates in fibrosis and scarring of the injured heart, complicating its use in regenerative medicine. Here, we report co-expression of TBX18 and WT1 in the majority of epicardial cells during mouse embryonic epicardial development...
December 7, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27926520/inhibiting-the-mnk-eif4e-%C3%AE-catenin-axis-increases-the-responsiveness-of-aggressive-breast-cancer-cells-to-chemotherapy
#8
Zhiqiang Li, Yang Sun, Miao Qu, Hongxing Wan, Fang Cai, Peng Zhang
Advanced breast cancer (eg. stage IV) is resistant to chemotherapy. In this work, we identified potentially druggable targets that are critically involved in chemoresistance. We showed that eIF4E is highly phosphorylated at serine 209 in breast cancer patients in response to chemotherapy, which significantly correlated with poorer clinical responses and outcomes. Depletion of eIF4E enhanced the anti-proliferative and pro-apoptotic effects of chemotherapeutic drugs in breast cancer cells. Chemotherapy activated the Wnt/β-catenin signaling in an eIF4E-dependent manner...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27924063/%C3%AE-np63%C3%AE-and-micrornas-leveraging-the-epithelial-mesenchymal-transition
#9
REVIEW
Andrew J Stacy, Michael P Craig, Suraj Sakaram, Madhavi Kadakia
The epithelial-mesenchymal transition (EMT) is a cellular reprogramming mechanism that is an underlying cause of cancer metastasis. Recent investigations have uncovered an intricate network of regulation involving the TGFβ, Wnt, and Notch signaling pathways and small regulatory RNA species called microRNAs (miRNAs). The activity of a transcription factor vital to the maintenance of epithelial stemness, ΔNp63α, has been shown to modulate the activity of these EMT pathways to either repress or promote EMT...
December 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27923660/highly-expressed-lncrna-ccnd2-as1-promotes-glioma-cell-proliferation-through-wnt-%C3%AE-catenin-signaling
#10
Hua Zhang, Lin D Wei, Long Wan, Feng S Yan, Hui Yan Sun
Glioma is the most common and aggressive primary brain tumor in adults. Long-non coding RNAs (lncRNAs) have been recently shown to play important roles in regulating numerous biological processes both in physiologic and pathologic condition. However, the role of lncRNAs in glioma remains largely unknown. In this study, we firstly found that lncRNA CCND2-AS2 is significantly up regulated in malignant glioma tissues and cell lines. Both loss- and gain-functions assays show that CCND2-AS1 promotes glioma cells proliferation and growth...
December 3, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27923410/supplementation-with-brazil-nuts-and-green-tea-extract-regulates-targeted-biomarkers-related-to-colorectal-cancer-risk-in-humans
#11
Ying Hu, Graeme H McIntosh, Richard K Le Leu, Roshini Somashekar, Xing Q Meng, Geetha Gopalsamy, Libby Bambaca, Ross A McKinnon, Graeme P Young
Se and green tea have been shown in epidemiological, observational and preclinical studies to be inversely related to the risk of developing colorectal cancer (CRC). However, there are limited studies to evaluate their regulatory effects on genes/proteins that relate to CRC oncogenesis in human subjects, such as selenoproteins, WNT signalling pathway, inflammation and methylation. This study examined the effects of supplementation of Se using Brazil nuts and green tea extract (GTE) capsules, alone and in combination, on targeted biomarkers...
December 7, 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/27922964/the-effect-of-uniaxial-mechanical-stretch-on-wnt-%C3%AE-catenin-pathway-in-bone-mesenchymal-stem-cells
#12
Chuang Zhao, Yunfeng Li, Xuemei Wang, Shujuan Zou, Jing Hu, En Luo
Wnt/β-catenin signal is required in bone formation and remodling, but little is known about whether Wnt/β-catenin signal could promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) after uniaxial mechanical stretch. In this study, rat BMSCs were identified by flow cytometry and used for mechanical stretch. A custom-made uniaxial dynamic stretch apparatus was applied for rat BMSCs stretch. There were 2 groups in the study: the mechanical stretch group and the nonstretch control group...
December 5, 2016: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/27921041/signaling-crosstalk-between-tubular-epithelial-cells-and-interstitial-fibroblasts-after-kidney-injury
#13
REVIEW
Roderick J Tan, Dong Zhou, Youhua Liu
BACKGROUND: A wide variety of kidney diseases ultimately lead to tubulointerstitial damage. The initial site of injury is usually the renal tubules, with activation of fibroblasts occurring later. Self-limited disease is characterized by transient cellular activation with timed deactivation and ultimately a return to normal functioning, whereas sustained responses characterize chronic disease and the development of irreversible fibrosis. The underlying molecular and cellular mechanisms of this cascade of events remain an area of active research...
October 2016: Kidney Diseases
https://www.readbyqxmd.com/read/27920883/exogenous-secreted-frizzled-related-protein-4-modulates-steroidogenesis-of-rat-granulosa-cells-through-wnt-%C3%AE-catenin-and-pi3k-akt-signaling-pathways
#14
Ghamartaj Hossein, Manijeh Khanmohammadi, Parisa Sahranavard Fard, Yasaman Heidarian, Somaieh Kazemnejad, Mohammad Mehdi Akhondi
BACKGROUND: It has been reported that secreted frizzled-related protein-4 known as an antagonist of Wnt signaling pathway plays a role in luteinization process of rodent granulosa cells. The purpose of this study was twofold: 1) to determine whether recombinant human secreted frizzled-related protein-4 (rhSFRP-4) could directly induce terminal differentiation of rat Granulosa Cells (GCs) and 2) to understand how the modulation of β-catenin and Protein Kinase B (PKB)/AKT activity by exogenous SFRP-4 could be involved in steroidogenesis...
October 2016: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/27920664/investigation-of-snp-rs2060546-immediately-upstream-to-ntn4-in-a-danish-gilles-de-la-tourette-syndrome-cohort
#15
Shanmukha S Padmanabhuni, Rayan Houssari, Ann-Louise Esserlind, Jes Olesen, Thomas M Werge, Thomas F Hansen, Birgitte Bertelsen, Fotis Tsetsos, Peristera Paschou, Zeynep Tümer
Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. GTS is a complex disorder, with environmental factors and several genes involved. Although variations within a few genes such as AADAC, NRXN1, SLITRK1, HDC, and IMMP2L have been tentatively associated with GTS (in a small number of patients), the causative genes underlying GTS pathophysiology remain unknown. In a previous genome-wide association study (GWAS) a single nucleotide polymorphism (SNP, rs2060546) near the Netrin-4 (NTN4 - MIM 610401) gene was shown to be associated with GTS [odds ratio (OR) = 1...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27920253/bmp-induces-osteoblast-differentiation-through-both-smad4-and-mtorc1-signaling
#16
Courtney M Karner, Seung-Yon Lee, Fanxin Long
The bone morphogenetic protein (Bmp) family of secreted molecules has been extensively studied in the context of osteoblast differentiation. However, the intracellular signaling cascades mediating the osteoblastogenic function of Bmp have not been fully elucidated. By profiling mRNA expression in the bone marrow mesenchymal progenitor cell line ST2 cells, we discover that BMP2 induces not only genes commonly associated with ossification and mineralization, but also genes important for general protein synthesis...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27919787/modulation-of-post-translational-modifications-in-%C3%AE-catenin-and-lrp6-inhibits-wnt-signaling-pathway-in-pancreatic-cancer
#17
Bharti Garg, Bhuwan Giri, Kaustav Majumder, Vikas Dudeja, Sulagna Banerjee, Ashok Saluja
β-catenin/Wnt Signaling pathway is critically regulated in a normal cell by a number of post-translational modifications. In pancreatic cancer however, aberrant activation of this pathway plays a significant role in tumor progression and metastasis. Though a number of studies have focused on understanding Wnt Signaling pathway in pancreatic cancer, there has been no systematic study to evaluate molecules that may be affecting this pathway. In the current study, we used a diterepende triepoxide, triptolide, to inhibit post-translational modifications in Wnt pathway and evaluated how this compound may be affecting the intricate signaling that regulates cell proliferation in pancreatic cancer...
December 2, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27919747/h19-mediates-methotrexate-resistance-in-colorectal-cancer-through-activating-wnt-%C3%AE-catenin-pathway
#18
Ke-Feng Wu, Wei-Cheng Liang, Lu Feng, Jian-Xin Pang, Mary Miu-Yee Waye, Jin-Fang Zhang, Wei-Ming Fu
Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. As one of the earliest cytotoxic drugs, methotrexate (MTX) serves as an anti-metabolite and anti-folate chemotherapy for various cancers. Unfortunately, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the therapeutic efficacy of MTX in clinics. Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years...
December 2, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27919074/epigenetic-stress-responses-induce-muscle-stem-cell-ageing-by-hoxa9-developmental-signals
#19
Simon Schwörer, Friedrich Becker, Christian Feller, Ali H Baig, Ute Köber, Henriette Henze, Johann M Kraus, Beibei Xin, André Lechel, Daniel B Lipka, Christy S Varghese, Manuel Schmidt, Remo Rohs, Ruedi Aebersold, Kay L Medina, Hans A Kestler, Francesco Neri, Julia von Maltzahn, Stefan Tümpel, K Lenhard Rudolph
The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell function during ageing, but the nature of this process remains poorly understood. Hox genes are key regulators of stem cells and tissue patterning during embryogenesis with an unknown role in ageing. Here we show that the epigenetic stress response in muscle stem cells (also known as satellite cells) differs between aged and young mice...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27917827/the-n14-anti-afamin-antibody-fab-a-rare-vl1-cdr-glycosylation-crystallographic-re-sequencing-molecular-plasticity-and-conservative-versus-enthusiastic-modelling
#20
Andreas Naschberger, Barbara G Fürnrohr, Tihana Lenac Rovis, Suzana Malic, Klaus Scheffzek, Hans Dieplinger, Bernhard Rupp
The monoclonal antibody N14 is used as a detection antibody in ELISA kits for the human glycoprotein afamin, a member of the albumin family, which has recently gained interest in the capture and stabilization of Wnt signalling proteins, and for its role in metabolic syndrome and papillary thyroid carcinoma. As a rare occurrence, the N14 Fab is N-glycosylated at Asn26L at the onset of the VL1 antigen-binding loop, with the α-1-6 core fucosylated complex glycan facing out of the L1 complementarity-determining region...
December 1, 2016: Acta Crystallographica. Section D, Structural Biology
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