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Dickkopf AND Wnt

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https://www.readbyqxmd.com/read/29131552/activation-of-the-wnt-pathway-by-small-peptides-rational-design-synthesis-and-biological-evaluation
#1
Simone Brogi, Samuele Maramai, Margherita Brindisi, Giulia Chemi, Valentina Porcari, Claudio Corallo, Luigi Gennari, Ettore Novellino, Anna Ramunno, Stefania Butini, Giuseppe Campiani, Sandra Gemma
A computational analysis of the X-ray structure of the low-density lipoprotein receptor-related protein 6 (LRP6) with Dickkopf-1 (DKK1) C-terminal fragment has allowed us to rationally design a small set of decapeptides (1a-e). These compounds behave as agonists of the canonical Wnt pathway in the micromolar range when tested on a dual luciferase Wnt functional assay in glioblastoma cells. Lack of cellular toxicity was assessed for compounds 1c and 1d in human primary osteoblasts isolated from sponge bone tissue (femoral heads or knee of old patients)...
November 13, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29131133/sulphonated-formononetin-induces-angiogenesis-through-vascular-endothelial-growth-factor-camp-response-element-binding-protein-early-growth-response-3-vascular-cell-adhesion-molecule-1-and-wnt-%C3%AE-catenin-signaling-pathway
#2
Zhaoju Dong, Yanan Shi, Huijuan Zhao, Ning Li, Liang Ye, Shuping Zhang, Haibo Zhu
BACKGROUND: Sodium formononetin-3'-sulphonate (Sul-F) is a derivative of the isoflavone formononetin. In this study, we investigated whether Sul-F can regulate angiogenesis and the potential mechanism in vitro. METHODS: We examined the effects of Sul-F on cell proliferation, cell invasion, and tube formation in the human umbilical vein endothelial cell line (HUVEC). To better understand the mechanism involved, we investigated effects of the following compounds: cAMP response element-binding protein (CREB) inhibitor 2-naphthol-AS-E-phosphate (KG-501), early growth response 3 (Egr-3) siRNA, vascular endothelial growth factor (VEGF) antagonist soluble VEGF receptor 1 (sFlt-1), VEGF receptor 2 blocker SU-1498, Wnt5a antagonist WIF-1 recombinant protein (WIF-1), and inhibitor of Wnt/β-catenin recombinant Dickkopf-1 protein (DKK-1)...
October 31, 2017: Pharmacology
https://www.readbyqxmd.com/read/29129760/the-key-role-of-proinflammatory-cytokines-matrix-proteins-rankl-opg-and-wnt-%C3%AE-catenin-in-bone-healing-of-hip-arthroplasty-patients
#3
Jean Cassuto, Agnetha Folestad, Jan Göthlin, Henrik Malchau, Johan Kärrholm
INTRODUCTION: We still lack understanding of why some implants fail while most remain stable after decades of use. Proinflammatory cytokines, matrix proteins and bone regulating cytokines of the RANKL/OPG (receptor activator of nuclear factor kappa B ligand/osteoprotegerin) and Wnt/β-catenin pathways are mandatory for normal bone repair but their spatial and temporal role in the healing of primary total hip arthroplasties (THA) has not been previously shown. MATERIALS AND METHODS: Twenty-four osteoarthritis patients with one-sided well-fixed primary THA were prospectively monitored during 18years (18Y) with repeated blood samples, clinical variables and radiographs...
November 9, 2017: Bone
https://www.readbyqxmd.com/read/29128813/effect-of-aromatase-inhibitors-on-learning-and-memory-and-modulation-of-hippocampal-dickkopf-1-and-sclerostin-in-female-mice
#4
Saima Zameer, Divya Vohora
BACKGROUND: There has been conflicting reports on the effect of third generation aromatase inhibitors on cognition in estrogen-deficient states. Since aromatase inhibitors themselves cause estrogen deprivation, the present work was designed to evaluate the comparative effect of three aromatase inhibitors on behavioral measures of learning and memory in female mice. Further, in view of the reports of estrogen and Wnt signaling pathway in cognition, the role of two Wnt signaling antagonists (dickkopf-1 and sclerostin) in mediation of cognitive effects of aromatase inhibitors was evaluated...
June 13, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29128706/consumption-of-ellagic-acid-and-dihydromyricetin-synergistically-protects-against-uv-b-induced-photoaging-possibly-by-activating-both-tgf-%C3%AE-1-and-wnt-signaling-pathways
#5
Na Rang Moon, Suna Kang, Sunmin Park
Ellagic acid (EGA) and dihydromyricetin (DHM) are both found in fruits and vegetables are used for anti-aging treatment for the skin. The anti-photoaging efficacy of EGA and DHM was investigated in UV-B irradiated skin in vivo and the involvement of transforming growth factor (TGF)-β1 and wnt signaling pathways were examined in vitro. HaCaT cells were treated with either 50μM EGA, 50μM DHM or 25μM EGA+25μM DHM before 100mJ/cm(2) UV-B exposure, and then oxidative stress and inflammation was measured. The involvement of TGF-β1 and wnt signaling was measured using their inhibitors, respectively, in HaCaT cells...
November 7, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29127399/radial-extracorporeal-shock-wave-therapy-enhances-the-proliferation-and-differentiation-of-neural-stem-cells-by-notch-pi3k-akt-and-wnt-%C3%AE-catenin-signaling
#6
Jing Zhang, Nan Kang, Xiaotong Yu, Yuewen Ma, Xining Pang
Neural stem cell (NSC) proliferation and differentiation play a pivotal role in the repair of brain function in central nervous system (CNS) diseases. Radial extracorporeal shock wave therapy (rESWT) is a non-invasive and innovative treatment for many conditions, yet little is known about the effects of this treatment on NSCs. Mouse NSCs (NE-4C) were exposed to rESWT with 1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 bar (500 impulses, and 2 Hz) in vitro. Cell viability test results indicated that rESWT, at a dose of 2...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121993/transcriptomic-analyses-reveal-the-underlying-pro-malignant-functions-of-pthr1-for-osteosarcoma-via-activation-of-wnt-and-angiogenesis-pathways
#7
Shenglong Li, Yujin Dong, Ke Wang, Zhe Wang, Xiaojing Zhang
BACKGROUND: Increasing evidence has indicated parathyroid hormone type 1 receptor (PTHR1) plays important roles for the development and progression of osteosarcoma (OS). However, its function mechanisms remain unclear. The goal of this study was to further illuminate the roles of PTHR1 in OS using microarray data. METHODS: Microarray data were available from the Gene Expression Omnibus database under the accession number GSE46861, including six tumors from mice with PTHR1 knockdown (PTHR1...
November 9, 2017: Journal of Orthopaedic Surgery and Research
https://www.readbyqxmd.com/read/29115514/polygonum-multiflorm-alleviates-glucocorticoid%C3%A2-induced-osteoporosis-and-wnt-signaling-pathway
#8
Manru Zhou, Jingkai Wu, Yongjie Yu, Yajun Yang, Jin Li, Liao Cui, Weimin Yao, Yuyu Liu
It is known that long‑term excessive administration of glucocorticoid (GC) results in osteoporosis. The present study aimed to evaluate the protective effects of Polygonum multiflorm (PM) on the bone tissue of rats with GC‑induced osteoporosis (GIO). A total of 90 6‑month‑old female Sprague Dawley rats (weight range, 190‑210 g) were randomly divided into nine groups: Control (normal saline); prednisone (GC; 6 mg·kg‑1·d‑1; Model); GC plus PMR30 (the 30% ethanol eluent fraction of PM) (H) (400 mg·kg‑1·d‑1); GC plus PMR30 (M) (200 mg·kg‑1·d‑1); GC plus PMR30 (L) (100 mg·kg‑1·d‑1); GC plus PMRF (fat‑soluble fraction of PM) (H) (400 mg·kg‑1·d‑1); GC plus PMRF (M) (200 mg·kg‑1·d‑1); GC plus PMRF (L) (100 mg·kg‑1·d‑1); GC plus calcitriol (CAL; 0...
November 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29107840/the-wnt-%C3%AE-catenin-signaling-in-endometriosis-the-expression-of-total-and-active-forms-of-%C3%AE-catenin-total-and-inactive-forms-of-glycogen-synthase-kinase-3%C3%AE-wnt7a-and-dickkopf-1
#9
Azar Pazhohan, Fardin Amidi, Firoozeh Akbari-Asbagh, Ensiyeh Seyedrezazadeh, Laya Farzadi, Mahshad Khodarahmin, Shayesteh Mehdinejadiani, Aligholi Sobhani
OBJECTIVES: The cyclical changes in proliferation and differentiation of endometrial cells are regulated by estrogen and progesterone via modulating Wnt/β-catenin signaling. Imbalance in the expression of estrogen and progesterone receptors causes progesterone resistance in endometriosis patients. The aim of this study was to investigate the expression of some main components of Wnt/β-catenin signaling including WNT7a, DKK-1, β-catenin, and GSK-3β in eutopic endometrium and peritoneal endometriotic lesions of endometriosis patients compared to healthy endometrium in the mid-secretory phase of menstrual cycle...
October 31, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/29098038/exogenous-dkk-3-reic-inhibits-wnt-%C3%AE-catenin-signaling-and-cell-proliferation-in-human-kidney-cancer-kpk1
#10
Jiaqi Xu, Takuya Sadahira, Rie Kinoshita, Shun-Ai Li, Peng Huang, Koichiro Wada, Motoo Araki, Kazuhiko Ochiai, Hirofumi Noguchi, Masakiyo Sakaguchi, Yasutomo Nasu, Masami Watanabe
The third member of the Dickkopf family (DKK-3), also known as reduced expression in immortalized cells (REIC), is a tumor suppressor present in a variety of tumor cells. Regarding the regulation of the Wnt/β-catenin signaling pathway, exogenous DKK-1 and DKK-2 are reported to inhibit Wnt signaling by binding the associated effectors. However, whether exogenous DKK-3 inhibits Wnt signaling remains unclear. A recombinant protein of human full-length DKK-3 was used to investigate the exogenous effects of the protein in vitro in KPK1 human renal cell carcinoma cells...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29073244/resveratrol-controlled-the-fate-of-porcine-pancreatic-stem-cells-through-the-wnt-%C3%AE-catenin-signaling-pathway-mediated-by-sirt1
#11
Shuanshuan Xu, Fen Sun, Lipeng Ren, Hong Yang, Na Tian, Sha Peng
Porcine pancreatic stem cells (PSCs) are considered promising transplant materials that may be used to treat diabetes, but some problems, such as insufficient cell number and low differentiation efficiency, should be solved before its clinical application. Resveratrol is a natural polyphenolic compound that can alleviate the complications of diabetes. In this study, we aimed to explore the specific effect of resveratrol on porcine PSCs. We treated porcine PSCs with 10 μM, 25 μM resveratrol to explore the effect of resveratrol on porcine PSCs...
2017: PloS One
https://www.readbyqxmd.com/read/29069652/protective-effect-of-curcumin-against-oxidative-stress-induced-injury-in-rats-with-parkinson-s-disease-through-the-wnt-%C3%AE-catenin-signaling-pathway
#12
Yun-Liang Wang, Bo Ju, Yu-Zhen Zhang, Hong-Lei Yin, Ya-Jun Liu, Shan-Shan Wang, Zhi-Lei Zeng, Xiao-Peng Yang, Hai-Tao Wang, Jin-Feng Li
BACKGROUND/AIMS: The study aimed to investigate the protective effect of curcumin against oxidative stress-induced injury of Parkinson's disease (PD) through the Wnt/β-catenin signaling pathway in rats. METHODS: The successfully established PD rat models and normal healthy rats were randomly assigned into the 6-hydroxydopamine (6-OHDA), the curcumin (Cur) and the control groups. Immunohistochemistry was used to detect the positive expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and glial fibrillary acidic protein (GFAP)...
October 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29055813/amyloid-%C3%AE-synaptotoxicity-is-wnt-pcp-dependent-and-blocked-by-fasudil
#13
Katherine J Sellers, Christina Elliott, Joshua Jackson, Anshua Ghosh, Elena Ribe, Ana I Rojo, Heledd H Jarosz-Griffiths, Iain A Watson, Weiming Xia, Mikhail Semenov, Peter Morin, Nigel M Hooper, Rod Porter, Jane Preston, Raya Al-Shawi, George Baillie, Simon Lovestone, Antonio Cuadrado, Michael Harte, Paul Simons, Deepak P Srivastava, Richard Killick
INTRODUCTION: Synapse loss is the structural correlate of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid β (Aβ) peptides aggregate to form senile plaques but as soluble peptides are toxic to synapses. We previously demonstrated that Aβ induces Dickkopf-1 (Dkk1), which in turn activates the Wnt-planar cell polarity (Wnt-PCP) pathway to drive tau pathology and neuronal death. METHODS: We compared the effects of Aβ and of Dkk1 on synapse morphology and memory impairment while inhibiting or silencing key elements of the Wnt-PCP pathway...
October 19, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29039525/the-association-between-parathyroid-hormone-1%C3%A2-34-and-the-wnt-%C3%AE-%C3%A2-catenin-signaling-pathway-in-a-rat-model-of-osteoarthritis
#14
Long Ma, Jiang Wu, Qun Hua Jin
The aim of the current study was to determine the effect of parathyroid hormone (PTH) 1‑34 on cartilage degeneration, and the association between PTH 1‑34 and factors associated with the Wnt/β‑catenin pathway following anterior cruciate ligament and medial meniscectomy‑induced osteoarthritis (OA) in rats. A total of 64 Sprague‑Dawley rats were randomly divided into the following four groups: Sham‑operated rats with normal saline (NS)‑treatment (n=16); anterior cruciate ligament transection with partial medial meniscectomy (ACLT + MMx) rats with NS‑treatment (n=16); sham‑operated rats treated with PTH 1‑34 (n=16); and ACLT + MMx rats treated with PTH 1‑34 (n=16)...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29029622/paracrine-and-autocrine-regulation-of-gene-expression-by-wnt-inhibitor-dickkopf-in-wild-type-and-mutant-hepatocytes
#15
Niklas Hartung, Uwe Benary, Jana Wolf, Bente Kofahl
BACKGROUND: Cells are able to communicate and coordinate their function within tissues via secreted factors. Aberrant secretion by cancer cells can modulate this intercellular communication, in particular in highly organised tissues such as the liver. Hepatocytes, the major cell type of the liver, secrete Dickkopf (Dkk), which inhibits Wnt/ β-catenin signalling in an autocrine and paracrine manner. Consequently, Dkk modulates the expression of Wnt/ β-catenin target genes. We present a mathematical model that describes the autocrine and paracrine regulation of hepatic gene expression by Dkk under wild-type conditions as well as in the presence of mutant cells...
October 13, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28981599/dkk4-knockdown-enhances-chemosensitivity-of-a549-dtx-cells-to-docetaxel
#16
Xueliang Yang, Yang Liu, Weina Li, Aimin Li, Quan Sun
Drug resistance greatly limits docetaxel efficiency in the treatment of non-small cell lung cancer (NSCLC). Dickkopf 4 (DKK4), a negative regulator of Wnt/β-catenin pathway, is believed to be involved in various human cancers; whereas the association of DKK4 with acquired docetaxel resistance in NSCLC remains unclear. In the present study, we investigated the involvement of DKK4 in the docetaxel-resistant human lung adenocarcinoma A549 (A549/DTX) cells. Our results showed that DKK4 expression was significantly increased in the A549/DTX cells compared with in the A549 cells, as well as in the culture supernatant of A549/DTX cells...
October 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28979801/the-role-of-dickkopf-family-in-cancers-from-bench-to-bedside
#17
REVIEW
You-Cheng Shao, Yan Wei, Jin-Fang Liu, Xiao-Yan Xu
Numerous epidemiological studies indicate that cancer will be responsible for millions of deaths in one year. Although multiple therapeutic strategies exist, and vast research efforts are being focused on developing newer and better regimens, cancer-related morbidity and mortality remain high. Metastasis and recurrence are prominent causes of treatment failure in cancers. Moreover, early diagnosis and treatment initiation are difficult to achieve in clinical practice. Fortunately, targeted therapy, which exerts its function at the molecular level, has proved to be greatly beneficial in several human diseases including cancers...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28978116/modulation-of-dkk-3-and-claudin-5-as-new-therapeutic-strategy-in-the-treatment-of-meningiomas
#18
Maria Caffo, Emanuela Esposito, Valeria Barresi, Gerardo Caruso, Salvatore M Cardali, Mariagrazia Rinaldi, Raffaella Mallamace, Michela Campolo, Giovanna Casili, Alfredo Conti, Antonino Germanò, Salvatore Cuzzocrea, Letteria Minutoli
Meningiomas are the most common tumors of the central nervous system, where the incidence is around 25% of all primary brain tumors. The optimal treatment is represented by total resection accompanied by the removal of the dura mater and bone when infiltrated by the tumor. The histological grading is the most important prognostic factor in the outcome. However, recurrences do occur in a significant proportion (10-25%) of cases, representing the most relevant clinical complication. Molecular therapies are providing to give different opportunities in the development of new treatments...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969056/suppression-of-mir-708-inhibits-the-wnt-%C3%AE-catenin-signaling-pathway-by-activating-dkk3-in-adult-b-all
#19
Yingjie Zhang, Huibo Li, Rongyi Cao, Lili Sun, Yan Wang, Shengjin Fan, Yanqiu Zhao, Desheng Kong, Lin Cui, Leilei Lin, Ke Wang, Yinghua Li, Jin Zhou
Inactivation of Dickkopf-3 (DKK3) is closely associated with a poor prognosis in various solid tumor and hematologic malignancies. Promoter hypermethylation is one potential cause of DKK3 inactivation. However, whether other mechanisms lead to DKK3 inactivation and the subsequent effects of these inactivations on cell proliferation and the Wnt signaling pathway in adult B acute lymphoblastic leukemia (B-ALL) remain unclear. In the present study, we found that low DKK3 expression levels were associated with high miR-708 expression and promoter hypermethylation in adult B-ALL...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28960195/doxycycline-induces-bone-repair-and-changes-in-wnt-signalling
#20
Kátia do Nascimento Gomes, Ana Paula Negreiros Nunes Alves, Paula Góes Pinheiro Dutra, Glauce Socorro de Barros Viana
Doxycycline (DOX) exhibits anti-inflammatory and MMP inhibitory properties. The objectives of this study were to evaluate the effects of DOX on alveolar bone repair. Controls (CTL) and DOX-treated (10 and 25 mg·kg(-1)) molars were extracted, and rats were killed 7 or 14 days later. The maxillae were processed and subjected to histological and immunohistochemical assays. Hematoxylin-eosin staining (7th day) revealed inflammation in the CTL group that was partly reversed after DOX treatment. On the 14th day, the CTL group exhibited bone neoformation, conjunctive tissue, re-epithelization and the absence of inflammatory infiltrate...
September 2017: International Journal of Oral Science
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