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Wnt activators

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https://www.readbyqxmd.com/read/27936013/%C3%AE-asarone-rescues-pb-induced-impairments-of-spatial-memory-and-synaptogenesis-in-rats
#1
Qian-Qian Yang, Wei-Zhen Xue, Rong-Xin Zou, Yi Xu, Yang Du, Shuang Wang, Lai Xu, Yuan-Zhi Chen, Hui-Li Wang, Xiang-Tao Chen
Chronic lead (Pb) exposure causes cognitive deficits. This study aimed to explore the neuroprotective effect and mechanism of β-asarone, an active component from Chinese Herbs Acorus tatarinowii Schott, to alleviate impairments of spatial memory and synaptogenesis in Pb-exposed rats. Both Sprague-Dawley developmental rat pups and adult rats were used in the study. Developmental rat pups were exposed to Pb throughout the lactation period and β-asarone (10, 40mg kg-1, respectively) was given intraperitoneally from postnatal day 14 to 21...
2016: PloS One
https://www.readbyqxmd.com/read/27934856/bulk-cell-density-and-wnt-tgfbeta-signalling-regulate-mesendodermal-patterning-of-human-pluripotent-stem-cells
#2
Henning Kempf, Ruth Olmer, Alexandra Haase, Annika Franke, Emiliano Bolesani, Kristin Schwanke, Diana Robles-Diaz, Michelle Coffee, Gudrun Göhring, Gerald Dräger, Oliver Pötz, Thomas Joos, Erik Martinez-Hackert, Axel Haverich, Falk F R Buettner, Ulrich Martin, Robert Zweigerdt
In vitro differentiation of human pluripotent stem cells (hPSCs) recapitulates early aspects of human embryogenesis, but the underlying processes are poorly understood and controlled. Here we show that modulating the bulk cell density (BCD: cell number per culture volume) deterministically alters anteroposterior patterning of primitive streak (PS)-like priming. The BCD in conjunction with the chemical WNT pathway activator CHIR99021 results in distinct paracrine microenvironments codifying hPSCs towards definitive endoderm, precardiac or presomitic mesoderm within the first 24 h of differentiation, respectively...
December 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27932350/role-of-noncanonical-wnts-signaling-pathway-in-human-aortic-valve-calcification
#3
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/27930333/tet-proteins-influence-the-balance-between-neuroectodermal-and-mesodermal-fate-choice-by-inhibiting-wnt-signaling
#4
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/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/27926520/inhibiting-the-mnk-eif4e-%C3%AE-catenin-axis-increases-the-responsiveness-of-aggressive-breast-cancer-cells-to-chemotherapy
#7
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/27926488/blocking-ezh2-methylation-transferase-activity-by-gsk126-decreases-stem-cell-like-myeloma-cells
#8
Delong Zeng, Maoxing Liu, Jingxuan Pan
EZH2 is a critical epigenetic regulator that is deregulated in various types of cancers including multiple myeloma (MM). In the present study, we hypothesized that targeting EZH2 might induce apoptosis in myeloma cells including stem cell-like cells (CSCs). We investigated the effect of EZH2 inhibition on MM cells using a potent inhibitor (GSK126). The results showed that GSK126 effectively abrogated the methylated histone 3 (H3K27me3) level in MM.1S and LP1 cells, and inhibited the number of live cells and colony formation in soft agar of six MM cell lines...
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/27922964/the-effect-of-uniaxial-mechanical-stretch-on-wnt-%C3%AE-catenin-pathway-in-bone-mesenchymal-stem-cells
#10
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
#11
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
#12
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/27920253/bmp-induces-osteoblast-differentiation-through-both-smad4-and-mtorc1-signaling
#13
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
#14
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
#15
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
#16
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/27916087/-the-regulatory-role-of-wnt-signaling-pathway-in-the-proliferation-and-activation-of-memory-t-cells
#17
Lei Luo, Guangheng Luo, Qian Fang, Shan Huang, Hui Chen
Objective To study the regulatory effect of Wnt signaling pathway on the activation and proliferation of memory T cells (TMs). Methods We established the mouse model of skin allograft transplantation (BALB/c-C57BL/6), and then we sorted and cultured immature dendritic cells (imDCs), mature dendritic cells (mDCs) and TMs from the C57BL/6 mice by immunomagnetic bead cell sorting. The imDCs or mDCs loading antigens from BALB/c mice were co-cultured with TMs in a 96-well plate or Transwell(TM) plate (MLR). The (3)H-TdR was used to detect the proliferation of TMs...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27914902/ppar%C3%AE-%C3%AE-a-master-regulator-of-mesenchymal-stem-cell-functions
#18
Farida Djouad, Natacha Ipseiz, Patricia Luz-Crawford, Carina Scholtysek, Gerhard Krönke, Christian Jorgensen
Peroxisome proliferator-activated receptors (PPARs) have emerged as key regulators of physiological and immunological processes. Recently, one of their members PPARβ/δ has been identified as major player in the maintenance of bone homeostasis, by promoting Wnt signalling activity in osteoblast and mesenchymal stem cells (MSC). PPARβ/δ not only controls the fate of MSC but also regulates their immunosuppressive properties by directly modulating their NF-κB activity. In this review, we discuss how the regulation of PPARβ/δ provides an innovative strategy for an optimisation of MSC-based therapy...
November 30, 2016: Biochimie
https://www.readbyqxmd.com/read/27914862/neurotensin-regulation-induces-overexpression-and-activation-of-egfr-in-hcc-and-restores-response-to-erlotinib-and-sorafenib
#19
Zherui Wu, Antoine Galmiche, Jin Liu, Nicolas Stadler, Dominique Wendum, Evelyne Segal-Bendirdjian, Valerie Paradis, Patricia Forgez
Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer due to the combination of late diagnosis and a lack of curative treatments. The identification of factors which promote tumor aggressiveness, and those that predict treatment responses, are a means to optimize the management of HCC patients. The complex of Neurotensin (NTS) and its high affinity receptor (NTSR1) has been shown to induce tumor growth and metastasis process in various cancers. In this paper, we propose that NTS and NTSR1 can assist in the management of HCC...
November 30, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27914705/pigment-epithelium-derived-factor-a-noninhibitory-serine-protease-inhibitor-is-renoprotective-by-inhibiting-the-wnt-pathway
#20
Xuemin He, Rui Cheng, Kyoungmin Park, Siribhinya Benyajati, Gennadiy Moiseyev, Chengyi Sun, Lorin E Olson, Yanhui Yang, Bonnie K Eby, Kai Lau, Jian-Xing Ma
Pigment epithelium-derived factor (PEDF) expression is downregulated in the kidneys of diabetic rats, and delivery of PEDF suppressed renal fibrotic factors in these animals. PEDF has multiple functions including anti-angiogenic, anti-inflammatory and antifibrotic activities. Since the mechanism underlying its antifibrotic effect remains unclear, we studied this in several murine models of renal disease. Renal PEDF levels were significantly reduced in genetic models of type 1 and type 2 diabetes (Akita and db/db, respectively), negatively correlating with Wnt signaling activity in the kidneys...
November 30, 2016: Kidney International
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