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Wnt activators

Lei Fang, Dedi Kong, Wei Xu
BACKGROUND: Thyroid cancer is the most common malignancy in human endocrine system. This study aimed to investigate the effects of microRNA-625-3p (miR-625-3p) on thyroid cancer cell proliferation, migration, invasion and apoptosis, as well as underlying potential mechanism. METHODS: The relative expressions of miR-625-3p in tumor tissues and adjacent normal tissues of 20 patients with papillary thyroid cancer (PTC) were assessed using qRT-PCR. Cell transfection was used to up-regulate or down-regulate the expressions of miR-625-3p in thyroid cancer SW579 and TPC-1 cells...
March 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Cuijun Deng, Huiying Zhu, Jiayi Li, Chun Feng, Qingqiang Yao, Liming Wang, Jiang Chang, Chengtie Wu
The cartilage lesion resulting from osteoarthritis (OA) always extends into subchondral bone. It is of great importance for simultaneous regeneration of two tissues of cartilage and subchondral bone. 3D-printed Sr5 (PO4 )2 SiO4 (SPS) bioactive ceramic scaffolds may achieve the aim of regenerating both of cartilage and subchondral bone. We hypothesized that strontium (Sr) and silicon (Si) ions released from SPS scaffolds play a crucial role in osteochondral defect reconstruction. Methods: SPS bioactive ceramic scaffolds were fabricated by a 3D-printing method...
2018: Theranostics
Zhejia Zhang, Xinying Li, Qian Xiao, Zhiming Wang
Thyroid cancer is the most frequently occurring type of endocrine tumor, with a rapidly increasing incidence rate. MicroRNA (miR)-574-5p is a candidate oncogene in various types of cancer. The present study identified that miR-574-5p affected the cell cycle distribution and apoptosis of BCPAP and FTC133 thyroid cancer cells via β-catenin/Wnt signaling by targeting Quaking proteins (QKIs). An MTT assay demonstrated that the knockdown of miR-574-5p suppressed the proliferation of the thyroid cancer cells. Fluorescence-activated cell sorting analysis demonstrated that the inhibition of miR-574-5p induced the G1 /S phase arrest and apoptosis of the cells...
April 2018: Oncology Letters
Yilin Jiang, Junjie Miao, Dongliang Wang, Jingru Zhou, Bo Liu, Feng Jiao, Jiangfeng Liang, Yangshuo Wang, Cungang Fan, Qingjun Zhang
Significant antitumor activity of Momordica anti-human immunodeficiency virus protein of 30 kDa (MAP30) purified from Momordica charantia has been the subject of previous research. However, the effective mechanism of MAP30 on malignant glioma cells has not yet been clarified. The aim of the present study was to investigate the effects and mechanism of MAP30 on U87 and U251 cell lines. A Cell Counting Kit-8 assay, wound healing assay and Transwell assay were used to detect the effects on U87 and U251 cells treated with different concentrations of MAP30 (0...
April 2018: Oncology Letters
Shweta Patel, Sarmita Jana, Rajlakshmi Chetty, Sonal Thakore, Man Singh, Ranjitsinh Devkar
Titanium dioxide nanoparticles (TiO2 NPs) are among abundantly used metal oxide NPs but their interactions with biomolecules and subsequent embryonic toxicity in higher vertebrates is not extensively reported. Physicochemical interactions of TiO2 NPs with egg albumen reveals that lower doses of TiO2 NPs (10 and 25 µg/ml) accounted for higher friccohesity and activation energy but an increment in molecular radii was recorded at higher doses (50 and 100 µg/ml). FTIR analysis revealed conformational changes in secondary structure of egg albumen as a result of electrostratic interactions between egg albumen and TiO2 NPs...
March 19, 2018: Scientific Reports
Jérome Chal, Ziad Al Tanoury, Masayuki Oginuma, Philippe Moncuquet, Bénédicte Gobert, Ayako Miyanari, Olivier Tassy, Getzabel Guevara, Alexis Hubaud, Agata Bera, Olga Sumara, Jean-Marie Garnier, Leif Kennedy, Marie Knockaert, Barbara Gayraud-Morel, Shahragim Tajbakhsh, Olivier Pourquié
Body skeletal muscles derive from the paraxial mesoderm, which forms in the posterior region of the embryo. Using microarrays, we characterize novel mouse presomitic mesoderm (PSM) markers and show that, unlike the abrupt transcriptome reorganization of the PSM, neural tube differentiation is accompanied by progressive transcriptome changes. The early paraxial mesoderm differentiation stages can be efficiently recapitulated in vitro using mouse and human pluripotent stem cells. While Wnt activation alone can induce posterior PSM markers, acquisition of a committed PSM fate and efficient differentiation into anterior PSM Pax3+ identity further requires BMP inhibition to prevent progenitors from drifting to a lateral plate mesoderm fate...
March 19, 2018: Development
Xiping Cheng, Sun Y Kim, Haruka Okamoto, Yurong Xin, George D Yancopoulos, Andrew J Murphy, Jesper Gromada
Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal function. Wnt/β-catenin signaling controls metabolic zonation by activating genes in the perivenous hepatocytes, while suppressing genes in the periportal counterparts. We now demonstrate that glucagon opposes the actions of Wnt/β-catenin signaling on gene expression and metabolic zonation pattern. The effects were more pronounced in the periportal hepatocytes where 28% of all genes were activated by glucagon and inhibited by Wnt/β-catenin...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
E Scarpa, A A Janeczek, A Hailes, M C de Andrés, A De Grazia, Roc Oreffo, T A Newman, N D Evans
Spatiotemporal control of drug delivery is important for a number of medical applications which may be achieved using polymersome nanoparticles (PMs). Wnt signalling is a molecular pathway activated in various physiological processes, including bone repair, that requires precise control of activation. Here, we hypothesise that PMs can be stably loaded with a small molecule Wnt agonist, 6-bromoindirubin-3'-oxime (BIO), and activate Wnt signalling promoting the osteogenic differentiation in human primary bone marrow stromal cells (BMSCs)...
March 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Jaesung Seo, Hyun Jung Kee, Hae-Ji Choi, Jae Eun Lee, Soo-Yeon Park, Seung-Hyun Lee, Mi-Hyeon Jeong, Garam Guk, SooYeon Lee, Kyung-Chul Choi, Yoon Young Choi, Hyunki Kim, Sung Hoon Noh, Ho-Geun Yoon, Jae-Ho Cheong
Wntless/GPR177 functions as WNT ligand carrier protein and activator of WNT/β-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n=184; GSE66229, n=300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n=909)...
March 20, 2018: BMB Reports
Gwang Hun Park, Hun Min Song, Su Bin Park, Ho-Jun Son, Yurry Um, Hyun-Seok Kim, Jin Boo Jeong
BACKGROUND: Because twigs of Cinnamomum cassia (TC) have been reported to exert anti-cancer activity, the mechanistic study for TC's anti-cancer activity is required. Thus, we elucidated the potential molecular mechanism of TC's anti-proliferative effect and the induction of apoptosis in human colorectal cancer cells. METHODS: How water extracts form TC (TC-HW) was used in this study. Anti-cell proliferative effect of TC-HW was evaluated by MTT assay. The change of protein or mRNA level by TC-HW was evaluated by Western blot and RT-RCR, respectively...
January 25, 2018: BMC Complementary and Alternative Medicine
Patrick J Atkinson, Yaodong Dong, Shuping Gu, Wenwen Liu, Elvis Huarcaya Najarro, Tomokatsu Udagawa, Alan G Cheng
During development, Sox2 is indispensable for cell division and differentiation, yet its roles in regenerating tissues are less clear. Here, we used combinations of transgenic mouse models to reveal that Sox2 haploinsufficiency (Sox2haplo) increases rather than impairs cochlear regeneration in vivo. Sox2haplo cochleae had delayed terminal mitosis and ectopic sensory cells, yet normal auditory function. Sox2haplo amplified and expanded domains of damage-induced Atoh1+ transitional cell formation in neonatal cochlea...
March 19, 2018: Journal of Clinical Investigation
Toshiaki Teratani, Kengo Tomita, Takahiro Suzuki, Hirotaka Furuhashi, Rie Irie, Makoto Nishikawa, Junji Yamamoto, Toshifumi Hibi, Soichiro Miura, Tohru Minamino, Yuichi Oike, Ryota Hokari, Takanori Kanai
Incidence of nonalcoholic steatohepatitis (NASH), which is considered a hepatic manifestation of metabolic syndrome, has been increasing worldwide with the rise in obesity; however, its pathological mechanism is poorly understood. Here, we demonstrate that the hepatic expression of aortic carboxypeptidase-like protein (ACLP), a glycosylated, secreted protein, increases in NASH in humans and mice. Furthermore, we elucidate that ACLP is a ligand, unrelated to WNT proteins, that activates the canonical WNT pathway and exacerbates NASH pathology...
March 19, 2018: Journal of Clinical Investigation
Ya-Ping Xiao, Jie Zeng, Lin-Na Jiao, Xiao-Yu Xu
The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
QiangYue Jiang, Lingyan Ma, RuiChao Li, JianHai Sun
The occurrence and development of colon cancer is closely related to inflammation. Therefore, this study was conducted a current retrospective research to study the effect of IL-35 (interleukin 35), a newly identified anti-infective factor, on colon cancer development. The expression of IL-35 in colon cancer samples and their adjacent normal mucosa by real-time PCR, ELISA (enzyme-linked immunosorbent assay). The effect of IL-35 on patient survival, colon cancer progression, and its effect on Wnt/β-catenine signaling pathway was also assessed...
February 23, 2018: Oncotarget
Fang Xu, Yingjie Zhu, Yuhong Lu, Zhi Yu, Jun Zhong, Yangqiu Li, Jingxuan Pan
Multiple myeloma (MM) is a malignancy of the bone marrow. The median survival time of patients with MM is only 5 years, with patients frequently experiencing relapse. Currently, there is no effective therapy for recurrent MM. The results of the present study indicated that pyrvinium pamoate (PP), a US Food and Drug Administration-approved oral anthelmintic drug, exhibited potent antitumor activity in MM cells in vitro . It is demonstrated that PP inhibited MM cell proliferation and mediated apoptosis. Notably, PP markedly promoted the degradation of β-catenin and abrogated its phosphorylation...
April 2018: Oncology Letters
Cheng-Fu Cai, Li-Man Liu, Han-Jing Shangguan, Cun-Shan Liu, Xian-Yang Luo, Yi-Meng Li
The Wnt/β-catenin pathway serves important roles in cancer development. The expression and function of Chibby (Cby), as a direct antagonist of β-catenin, in nasopharyngeal carcinoma (NPC) has not been fully investigated. The present study revealed that the mRNA and protein expression of Cby was significantly lower in NPC tissue than in the adjacent normal tissue. Low expression of Cby was significantly associated with the tumor and the clinical staging. Furthermore, Cby overexpression inhibited the proliferation of human NPC SUNE1 cells and induced cell cycle arrest...
April 2018: Oncology Letters
Concetta Saponaro, Sara Sergio, Antonio Coluccia, Maria De Luca, Giuseppe La Regina, Luca Mologni, Valeria Famiglini, Valentina Naccarato, Daniela Bonetti, Candice Gautier, Stefano Gianni, Daniele Vergara, Michel Salzet, Isabelle Fournier, Cecilia Bucci, Romano Silvestri, Carlo Gambacorti Passerini, Michele Maffia, Addolorata Maria Luce Coluccia
Nuclear activated β-catenin plays a causative role in colorectal cancers (CRC) but remains an elusive therapeutic target. Using human CRC cells harboring different Wnt/β-catenin pathway mutations in APC/KRAS or β-catenin/KRAS genes, and both genetic and pharmacological knockdown approaches, we show that oncogenic β-catenin signaling negatively regulates the expression of NHERF1 (Na+ /H+ exchanger 3 regulating factor 1), a PDZ-adaptor protein that is usually lost or downregulated in early dysplastic adenomas to exacerbate nuclear β-catenin activity...
March 19, 2018: Oncogene
Long Cui, Juan Zhao, Jingjing Liu
BACKGROUND: Aberrant Wnt/β-catenin activation has been shown to play essential roles in cancer, including renal cell carcinoma (RCC). In this work, we demonstrate that Wnt/β-catenin inhibition by a Food and Drug Administration-approved drug, pyrvinium, effectively targets clear cell RCC and enhances chemotherapy agent's efficacy. MATERIALS AND METHODS: We performed in vitro cell culture assays and in vivo xenograft tumor model to evaluate the effects of pyrvinium alone and its combination with paclitaxel, and analyzed the underlying mechanism(s) of pyrvinium's action in RCC...
March 2018: American Journal of the Medical Sciences
A Premanand, B Reena Rajkumari
Androgenetic alopecia (AGA) is a dermatological disorder of scalp hair loss characterized by a progressive miniaturization of hair follicles with shortened anagen phase leading to a decreased number of hairs on the scalp. It is a complex polygenic trait prevailing around two-thirds of the male population. Elevated expressions of 5α-dihydrotestosterone and androgen receptor are the causal factors for AGA. This review describes recent studies on the role of androgens and androgen receptor (AR) transactivation activity in modulating the Wnt/β-catenin signaling in the dermal papilla cells of the balding scalp in androgenetic alopecia...
March 16, 2018: Archives of Dermatological Research
Amelia Weber Hall, Anna M Battenhouse, Haridha Shivram, Adam R Morris, Matthew C Cowperthwaite, Max Shpak, Vishwanath R Iyer
Glioblastoma multiforme (GBM) can be clustered by gene expression into four main subtypes associated with prognosis and survival, but enhancers and other gene regulatory elements have not yet been identified in primary tumors. Here, we profiled six histone modifications and CTCF binding as well as gene expression in primary gliomas, and identified chromatin states that define distinct regulatory elements across the tumor genome. Enhancers in mesenchymal and classical tumor subtypes drove gene expression associated with cell migration and invasion, while enhancers in proneural tumors controlled genes associated with a less aggressive phenotype in GBM...
March 16, 2018: Cancer Research
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