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https://www.readbyqxmd.com/read/28938435/the-role-of-sequential-bmp-signaling-in-directing-human-embryonic-stem-cells-to-bipotential-gonadal-cells
#1
Kirsi Sepponen, Karolina Lundin, Katri Knuus, Pia Väyrynen, Taneli Raivio, Juha S Tapanainen, Timo Tuuri
Context: Human gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but due to a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed. Objective: Our objective was to establish an in vitro method for studying differentiation of bipotential gonadal progenitors using human embryonic stem cells (hESCs), and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation...
August 29, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28937990/treatment-of-opg-deficient-mice-with-wp9qy-a-rankl-binding-peptide-recovers-alveolar-bone-loss-by-suppressing-osteoclastogenesis-and-enhancing-osteoblastogenesis
#2
Yuki Ozaki, Masanori Koide, Yuriko Furuya, Tadashi Ninomiya, Hisataka Yasuda, Midori Nakamura, Yasuhiro Kobayashi, Naoyuki Takahashi, Nobuo Yoshinari, Nobuyuki Udagawa
Osteoblasts express two key molecules for osteoclast differentiation, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), a soluble decoy receptor for RANKL. RANKL induces osteoclastogenesis, while OPG inhibits it by blocking the binding of RANKL to RANK, a cellular receptor of RANKL. OPG-deficient (OPG-/-) mice exhibit severe alveolar bone loss with enhanced bone resorption. WP9QY (W9) peptide binds to RANKL and blocks RANKL-induced osteoclastogenesis. W9 is also reported to stimulate bone formation in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28931883/high-throughput-targeted-screening-in-triple-negative-breast-cancer-cells-identifies-wnt-inhibiting-activities-in-pacific-brittle-stars
#3
Artem Blagodatski, Vsevolod Cherepanov, Alexey Koval, Vladimir I Kharlamenko, Yuri S Khotimchenko, Vladimir L Katanaev
Pro-proliferative oncogenic signaling is one of the hallmarks of cancer. Specific targeting of such signaling pathways is one of the main approaches to modern anti-cancer drug discovery, as opposed to more traditional search for general cytotoxic agents. Natural products, especially from marine sources, represent a largely untapped source of chemical diversity, which so far have mostly been screened for cytotoxicity. Here we present a pioneering pipeline of high-throughput screening of marine-based activities targeted against the Wnt signaling pathway, which is one of the key factors in oncogenic transformation, growth and metastasis in different cancers, including the devastating triple-negative breast cancer (TNBC) currently lacking any targeted therapies...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931847/excessive-activation-of-tlr4-nf-%C3%AE%C2%BAb-interactively-suppresses-the-canonical-wnt-%C3%AE-catenin-pathway-and-induces-sanfh-in-sd-rats
#4
Junpeng Pei, Lihong Fan, Kai Nan, Jia Li, Zhibin Shi, Xiaoqian Dang, Kunzheng Wang
Nuclear factor-kappa B (NF-κB) interactively affects the Wnt/β-catenin pathway and is closely related to different diseases. However, such crosstalk effect in steroid-associated necrosis of femoral head (SANFH) has not been fully explored and evaluated. In this study, early-stage SANFH was induced by two doses of lipopolysaccharide (LPS, 2 mg/kg/day) and three doses of methylprednisolone (MPS, 40 mg/kg/day). LPS and pyrrolidine dithiocarbamate (PDTC) were administered to activate the TLR4/NF-κB pathway and selectively block the activation of NF-κB, respectively...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28930145/to-wnt-or-lose-the-missing-non-coding-linc-in-colorectal-cancer
#5
REVIEW
Peng Shen, Martin Pichler, Meng Chen, George A Calin, Hui Ling
Colorectal cancer (CRC) is the third most frequent cancer and one of the leading causes for cancer-related mortality. Aberrant activation of the Wnt signaling is an essential initiating factor in colon carcinogenesis, and a driving force of CRC progression. Recently, long non-coding RNAs (lncRNAs) have emerged as significant players in CRC pathogenesis through diversified mechanisms. Although both Wnt signaling and lncRNAs represent interesting research areas for CRC, an effort of directly connecting these two areas is lacking...
September 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28929374/inhibition-of-gsk-3%C3%AE-activation-protects-sd-rat-retina-against-n-methyl-n-nitrosourea-induced-degeneration-by-modulating-the-wnt-%C3%AE-catenin-signaling-pathway
#6
Baoying Wang, Chenghu Hu, Xiaobei Yang, Fangying Du, Yan Feng, Hongbo Li, Chunhui Zhu, Xiaorui Yu
Retinal degenerative diseases are characterized by photoreceptor cell loss. Photoreceptor cell loss leading to retinal degeneration can be induced by N-methyl-N-nitrosourea (MNU), which was widely used to mimic the pathology. However, the mechanism by which MNU induces photoreceptor cell loss is still largely unknown. The purpose of the present study was to investigate whether phosphorylation of glycogen synthase kinase-3β (p-GSK-3β) is a potent mediator of MNU-induced retinal degeneration and how p-GSK-3β affects the process...
September 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28928248/carbonic-anhydrase-iii-protects-osteocytes-from-oxidative-stress
#7
Chao Shi, Yuhei Uda, Christopher Dedic, Ehab Azab, Ningyuan Sun, Amira I Hussein, Christopher A Petty, Keertik Fulzele, Maria C Mitterberger-Vogt, Werner Zwerschke, Renata Pereira, Kunzheng Wang, Paola Divieti Pajevic
Osteocytes are master orchestrators of bone remodeling; they control osteoblast and osteoclast activities both directly via cell-to-cell communication and indirectly via secreted factors, and they are the main postnatal source of sclerostin and RANKL (receptor activator of NF-kB ligand), two regulators of osteoblast and osteoclast function. Despite progress in understanding osteocyte biology and function, much remains to be elucidated. Recently developed osteocytic cell lines-together with new genome editing tools-has allowed a closer look at the biology and molecular makeup of these cells...
September 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28926938/integrin-activation-contributes-to-lower-cisplatin-sensitivity-in-mv3-melanoma-cells-by-inducing-the-wnt-signalling-pathway
#8
Maria B R Piva, Bastian Jakubzig, Gerd Bendas
BACKGROUND: integrins have been associated with the development of chemotherapy resistant tumour cells, mostly those of hematopoietic origin, by mediating the binding to the extracellular matrix. The relevance for solid tumour cells and the underlying mechanisms remain elusive. METHODS: using MTT assays, we detected the loss in cisplatin sensitivity of human MV3 melanoma cells upon integrin activation. Underlying cellular pathways were evaluated by flow cytometry...
September 16, 2017: Cancers
https://www.readbyqxmd.com/read/28926590/fluoxetine-ameliorates-cartilage-degradation-in-osteoarthritis-by-inhibiting-wnt-%C3%AE-catenin-signaling
#9
Kentaro Miyamoto, Bisei Ohkawara, Mikako Ito, Akio Masuda, Akihiro Hirakawa, Tadahiro Sakai, Hideki Hiraiwa, Takashi Hamada, Naoki Ishiguro, Kinji Ohno
Abnormal activation of the Wnt/β-catenin signaling is implicated in the osteoarthritis (OA) pathology. We searched for a pre-approved drug that suppresses abnormally activated Wnt/β-catenin signaling and has a potency to reduce joint pathology in OA. We introduced the TOPFlash reporter plasmid into HCS-2/8 human chondrosarcoma cells to estimate the Wnt/β-catenin activity in the presence of 10 μM each compound in a panel of pre-approved drugs. We found that fluoxetine, an antidepressant in the class of selective serotonin reuptake inhibitors (SSRI), down-regulated Wnt/β-catenin signaling in human chondrosarcoma cells...
2017: PloS One
https://www.readbyqxmd.com/read/28926578/tet-mediated-dna-hydroxymethylation-regulates-retinal-neurogenesis-by-modulating-cell-extrinsic-signaling-pathways
#10
Pawat Seritrakul, Jeffrey M Gross
DNA hydroxymethylation has recently been shown to play critical roles in regulating gene expression and terminal differentiation events in a variety of developmental contexts. However, little is known about its function during eye development. Methylcytosine dioxygenases of the Tet family convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an epigenetic mark thought to serve as a precursor for DNA demethylation and as a stable mark in neurons. Here, we report a requirement for Tet activity during zebrafish retinal neurogenesis...
September 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28926092/key-genes-regulating-the-liposecretion-process-of-mature-adipocytes
#11
Giulia Maurizi, Tiina Petäistö, Angela Maurizi, Lucio Della Guardia
White mature adipocytes (MAs) are plastic cells able to reversibly transdifferentiate toward fibroblast-like cells maintaining stem cell gene signatures. The main morphologic aspect of this transdifferentiation process, called liposecretion, is the secretion of large lipid droplets and the development of organelles necessary for exocrine secretion. There is a considerable interest in the adipocyte plastic properties involving liposecretion process, but the molecular details are incompletely explored. This review analyzes the gene expression of MAs isolated from human subcutaneous fat tissue with respect to bone marrow (BM)-derived mesenchymal stem cells (MSC) focusing on gene regulatory pathways involved into cellular morphology changes, cellular proliferation and transports of molecules through the membrane, suggesting potential ways to guide liposecretion...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28926089/long-non-coding-rna-linc00968-acts-as-oncogene-in-nsclc-by-activating-the-wnt-signaling-pathway
#12
Yíng Wang, Jun Zhou, Yu-Jun Xu, Hai-Bo Hu
Long non-coding RNAs (lncRNAs) have played critical roles in a variety of cancers, including non-small cell lung cancer (NSCLC). In our study, we focused on the biological function and clinical significance of lncRNA LINC00968 in NSCLC. It was indicated that LINC00968 was significantly increased in LUAD tissues, LUSC tissues and NSCLC cells compared to their corresponding controls. Inhibition of LINC00968 was able to repress NSCLC growth, migration and invasion in vitro while upregulation of LINC00968 reversed this process...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28923859/upregulation-of-cystathionine-%C3%AE-synthase-in-colonic-epithelia-reprograms-metabolism-and-promotes-carcinogenesis
#13
Ches'Nique M Phillips, John Zatarain, Michael E Nicholls, Craig Porter, Steve G Widen, Ketan Thanki, Paul Johnson, Muhammad U Jawad, Mary Pat Moyer, James W Randall, Judith L Hellmich, Manjit Maskey, Suimin Qiu, Thomas Wood, Nadiya Druzhyna, Bartosz Szczesny, Katalin Modis, Csaba Szabo, Celia Chao, Mark R Hellmich
The transsulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923827/mutant-ctnnb1-and-histological-heterogeneity-define-metabolic-subtypes-of-hepatoblastoma
#14
Stefania Crippa, Pierre-Benoit Ancey, Jessica Vazquez, Paolo Angelino, Anne-Laure Rougemont, Catherine Guettier, Vincent Zoete, Mauro Delorenzi, Olivier Michielin, Etienne Meylan
Hepatoblastoma is the most common malignant pediatric liver cancer. Histological evaluation of tumor biopsies is used to distinguish among the different subtypes of hepatoblastoma, with fetal and embryonal representing the two main epithelial components. With frequent CTNNB1 mutations, hepatoblastoma is a Wnt/β-catenin-driven malignancy. Considering that Wnt activation has been associated with tumor metabolic reprogramming, we characterized the metabolic profile of cells from hepatoblastoma and compared it to cells from hepatocellular carcinoma...
September 18, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28923486/retinoic-acid-is-required-and-fgf-wnt-and-bmp-signaling-inhibit-posterior-lateral-line-placode-induction-in-zebrafish
#15
Masataka Nikaido, Joaquin Navajas Acedo, Kohei Hatta, Tatjana Piotrowski
The lateral line system is a mechanosensory systems present in aquatic animals. The anterior and posterior lateral lines develop from anterior and posterior lateral line placodes (aLLp and pLLp), respectively. Although signaling molecules required for the induction of other cranial placodes have been well studied, the molecular mechanisms underlying formation of the lateral line placodes are unknown. In this study we tested the requirement of multiple signaling pathways, such as Wnt, Bmp Fgf, and Retinoic Acid for aLLp and pLLp induction...
September 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28922975/bioengineered-submucosal-organoids-for-in-vitro-modeling-of-colorectal-cancer
#16
Mahesh Devarasetty, Aleksander Skardal, Kyle Cowdrick, Frank Marini, Shay Soker
The physical nature of the tumor microenvironment significantly impacts tumor growth, invasion and response to drugs. Most in vitro tumor models are designed to study the effects of extracellular matrix (ECM) stiffness on tumor cells, while not addressing the effects of ECM's specific topography. In this study we bioengineered submucosal organoids, using primary smooth muscle cells (SMCs) embedded in collagen I (Col I) hydrogel, which produce aligned and parallel fiber topography similar to those found in vivo...
September 19, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28922151/dickkopf-3-dkk3-improves-amyloid-%C3%AE-pathology-cognitive-dysfunction-and-cerebral-glucose-metabolism-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#17
Li Zhang, Caixian Sun, Yaxi Jin, Kai Gao, Xudong Shi, Wenying Qiu, Chao Ma, Lianfeng Zhang
Dysfunctional Wnt signaling is associated with Alzheimer's disease (AD), and activation of the Wnt signaling pathway inhibits AD development. Dickkopf 3 (Dkk3) is a modulator of the Wnt signaling pathway and is physiologically expressed in the brain. The role of Dkk3 in the pathogenesis of AD has not been evaluated. In the present study, we determined that Dkk3 expression was significantly decreased in brain tissue from AD patients and the AD transgenic mouse model APPswe/PS1dE9 (AD mice). Transgenic mice with brain tissue-specific Dkk3 expression were generated or crossed with AD mice to study the effects of Dkk3 on AD...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28921929/tumor-suppressive-mir-145-co-repressed-by-tcf4-%C3%AE-catenin-and-prc2-complexes-forms-double-negative-regulation-loops-with-its-negative-regulators-in-colorectal-cancer
#18
Wei Wang, Xin Xiao, Xu Chen, Yi Huo, Wen-Jin Xi, Zhi-Feng Lin, Dan Zhang, Yu-Fang Li, Fan Yang, Wei-Hong Wen, An-Gang Yang, Tao Wang
The frequently dysregulated Wnt/β-catenin signaling in different malignancies, by activation of its own or orchestration with other co-factors, regulates various oncogenic or tumor-suppressive genes. Among these genes, miRNAs, which are negative posttranscriptional regulators, are also embedded in the Wnt signaling network. Different from the Wnt-induced oncogenic miRNAs, the specific mechanism underlying the Wnt-repressed tumor-suppressive miRNAs is much less understood. In the present study, firstly by analyzing a ChIP-seq dataset against TCF4, the core transcription factor for initiation of Wnt signaling in colorectal cancer (CRC) cells, we screened out several tumor-suppressive miRNAs potentially regulated by Wnt signaling...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28921615/plasticizer-di-2-ethylhexyl-phthalate-interferes-with-osteoblastogenesis-and-adipogenesis-in-a-mouse-model
#19
Chen-Yuan Chiu, Shih-Chun Sun, Chih-Kang Chiang, Ching-Chia Wang, Ding-Cheng Chan, Huang-Jen Chen, Shing-Hwa Liu, Rong-Sen Yang
Plasticizer di(2-ethylhexyl)phthalate (DEHP) can leach from medical devices such as blood storage bags and the tubing. Recently, epidemiological studies showed that phthalate metabolites levels in the urine are associated with low bone mineral density (BMD) in older women. The detailed effect and mechanism of DEHP on osteoblastogenesis and adipogenesis and bone loss remain to be clarified. Here, we investigated the effect and mechanism of DEHP and its active metabolite mono(2 -ethylhexyl)phthalate (MEHP) on osteoblastogenesis and adipogenesis...
September 16, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28920943/expression-function-and-regulation-of-the-embryonic-transcription-factor-tbx1-in-parathyroid-tumors
#20
Chiara Verdelli, Laura Avagliano, Vito Guarnieri, Filomena Cetani, Stefano Ferrero, Leonardo Vicentini, Edoardo Beretta, Alfredo Scillitani, Pasquale Creo, Gaetano Pietro Bulfamante, Valentina Vaira, Sabrina Corbetta
Transcription factors active in embryonic parathyroid cells can be maintained in adult parathyroids and be involved in tumorigenesis. TBX1, the candidate gene of 22q11.2-DiGeorge syndrome, which includes congenital hypoparathyroidism, is involved in parathyroid embryogenesis. The study aimed to investigate expression, function, and regulation of the parathyroid embryonic transcription factor TBX1 in human parathyroid adult normal and tumor tissues. TBX1 transcripts were detected in normal parathyroids and were deregulated in parathyroid tumors...
September 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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