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https://www.readbyqxmd.com/read/28318631/the-antihelmenthic-phosphate-niclosamide-impedes-renal-fibrosis-by-inhibiting-homeodomain-interacting-protein-kinase-2-expression
#1
Xiaoyan Chang, Xin Zhen, Jixing Liu, Xiaomei Ren, Zheng Hu, Zhanmei Zhou, Fengxin Zhu, Ke Ding, Jing Nie
Renal fibrosis is the final common pathway of all varieties of progressive chronic kidney disease. However, there are no effective therapies to prevent or slow the progression of renal fibrosis. Niclosamide is a US Food and Drug Administration-approved oral antihelminthic drug used for treating most tapeworm infections. Here, we demonstrated that phosphate niclosamide, the water-soluble form of niclosamide, significantly reduced proteinuria, glomerulosclrotic lesions, and interstitial fibrosis in a murine model of adriamycin nephropathy...
March 16, 2017: Kidney International
https://www.readbyqxmd.com/read/28315733/wt1-ameliorates-podocyte-injury-via-repression-of-ezh2-%C3%AE-catenin-pathway-in-diabetic-nephropathy
#2
Jiao Wan, Xiaoyan Hou, Zhanmei Zhou, Jian Geng, Jianwei Tian, Jing Nie, Xiaoyan Bai
Epigenetic modulation of podocyte injury plays a pivotal role in diabetic nephropathy (DN). Wilm's tumor 1 (WT1) has been found to have opposing roles with β-catenin in podocyte biology. Herein, we asked whether the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) promotes WT1-induced podocyte injury via β-catenin activation and the underlying mechanisms. We found that WT1 antagonized EZH2 and ameliorated β-catenin-mediated podocyte injury as demonstrated by attenuated podocyte mesenchymal transition, maintenance of podocyte architectural integrity, decreased podocyte apoptosis and oxidative stress...
March 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28315345/inositol-hexaphosphate-suppresses-colorectal-cancer-cell-proliferation-via-the-akt-gsk-3%C3%AE-%C3%AE-catenin-signaling-cascade-in-a-1-2-dimethylhydrazine-induced-rat-model
#3
Wenyang Yu, Cuiping Liu, Xin Li, Fuguo Yang, Lixue Cheng, Chang Liu, Yang Song
Colorectal cancer (CRC) is common worldwide, and most treatments for CRC have undesirable side effects. Many researchers have demonstrated that inositol hexaphosphate (IP6) has potent anticarcinogenic activity against CRC and no apparent toxicity to normal cells. However, the underlying mechanism is still unclear. In this study, we investigated the anticancer and anti-proliferative properties of IP6 in CRC and its possible mechanisms during this chemopreventive process. We examined the expression of genes related to the PI3K/Akt and Wnt pathways at the transcriptional and translational levels in a DMH-induced rat CRC model following IP6 administration...
March 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28304136/zebrafish-models-of-non-canonical-wnt-planar-cell-polarity-signalling-fishing-for-valuable-insight-into-vertebrate-polarized-cell-behavior
#4
REVIEW
Maria Jussila, Brian Ciruna
Planar cell polarity (PCP) coordinates the uniform orientation, structure and movement of cells within the plane of a tissue or organ system. It is beautifully illustrated in the polarized arrangement of bristles and hairs that project from specialized cell surfaces of the insect abdomen and wings, and pioneering genetic studies using the fruit fly, Drosophila melanogaster, have defined a core signalling network underlying PCP. This core PCP/non-canonical Wnt signalling pathway is evolutionarily conserved, and studies in zebrafish have helped transform our understanding of PCP from a peculiarity of polarized epithelia to a more universal cellular property that orchestrates a diverse suite of polarized cell behaviors that are required for normal vertebrate development...
March 17, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28303973/e6-e7-p53-pou2f1-cthrc1-axis-promotes-cervical-cancer-metastasis-and-activates-wnt-pcp-pathway
#5
Rong Zhang, Huan Lu, Yuan-Yuan Lyu, Xiao-Mei Yang, Lin-Yan Zhu, Guang-Dong Yang, Peng-Cheng Jiang, Yuan Re, Wei-Wei Song, Jin-Hao Wang, Can-Can Zhang, Fei Gu, Tian-Jiao Luo, Zhi-Yong Wu, Cong-Jian Xu
Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303901/mutual-reinforcement-between-telomere-capping-and-canonical-wnt-signalling-in-the-intestinal-stem-cell-niche
#6
Ting-Lin B Yang, Qijun Chen, Jennifer T Deng, Geetha Jagannathan, John W Tobias, David C Schultz, Shan Wang, Christopher J Lengner, Anil K Rustgi, John P Lynch, F Brad Johnson
Critical telomere shortening (for example, secondary to partial telomerase deficiency in the rare disease dyskeratosis congenita) causes tissue pathology, but underlying mechanisms are not fully understood. Mice lacking telomerase (for example, mTR(-/-) telomerase RNA template mutants) provide a model for investigating pathogenesis. In such mice, after several generations of telomerase deficiency telomeres shorten to the point of uncapping, causing defects most pronounced in high-turnover tissues including intestinal epithelium...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28302747/glutathione-peroxidase-4-inhibits-wnt-%C3%AE-catenin-signaling-and-regulates-dorsal-organizer-formation-in-zebrafish-embryos
#7
Xiaozhi Rong, Yumei Zhou, Yunzhang Liu, Beibei Zhao, Bo Wang, Caixia Wang, Xiaoxia Gong, Peipei Tang, Ling Lu, Yun Li, Chengtian Zhao, Jianfeng Zhou
The Wnt/β-catenin signaling pathway plays pivotal roles in axis formation during embryogenesis and in adult tissue homeostasis. Glutathione peroxidase 4 (GPx4) is a selenoenzyme and participates in the reduction of peroxides. Its synthesis depends on the availability of the element selenium. However, the roles of GPx4 in vertebrate embryonic development and underlying mechanisms are largely unknown. Here, we show that maternal loss of zebrafish gpx4b promotes embryonic dorsal organizer formation, whereas overexpression of GPx4b inhibits the development of the dorsal organizer...
March 16, 2017: Development
https://www.readbyqxmd.com/read/28300597/gli2-is-a-regulator-of-%C3%AE-catenin-and-is-associated-with-loss-of-e-cadherin-cell-invasiveness-and-long-term-epidermal-regeneration
#8
Eleni Pantazi, Emilios Gemenetzidis, Muy-Teck Teh, Sreekanth Vootukuri Reddy, Gary Warnes, Chris Evagora, Giuseppe Trigiante, Michael P Philpott
Uncontrolled HH/GLI and WNT/β-catenin signaling are important events in the genesis of many cancers including skin cancer and are often implicated in tumour progression, invasion and metastasis. However, due to the complexity and context-dependency of both pathways, little is known about HH and WNT interactions in human carcinogenesis. In the current study we provide evidence of HH/GLI2-WNT/β-catenin signaling crosstalk in human keratinocytes. Over-expression of GLI2ΔN in human keratinocytes resulted in cytoplasmic accumulation and nuclear relocalization of β-catenin in vitro and in 3D-organotypic cultures, accompanied by upregulation of WNT genes...
March 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28300286/clinical-significance-and-prognosis-value-of-wnt-signaling-pathway-in-cervical-cancer
#9
Afsane Bahrami, Malihe Hasanzadeh, Soodabeh ShahidSales, Zohre Yousefi, Sima Kadkhodayan, Marjaneh Farazestanian, Mona Joudi Mashhad, Masoumeh Gharib, Seyed Mahdi Hassanian, Amir Avan
Cervical cancer is among the most commonly diagnosed cancer in women, supporting the need for identification of novel prognostic and predictive biomarkers to predict the risk of developing of this malignancy or predict the prognosis of patients. Against this background, the activation of the Wingless-type (Wnt)/β-catenin pathway has been suggested as the main dysregulated pathways, which is involved in the multistep process of cervical carcinogenesis, suggesting its value as a potential biomarker or therapeutic target...
March 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28300015/frzb-and-melusin-overexpressed-in-lgmd2a-regulate-integrin-%C3%AE-1d-isoform-replacement-altering-myoblast-fusion-and-the-integrin-signalling-pathway
#10
Oihane Jaka, Leire Casas-Fraile, Margarita Azpitarte, Ana Aiastui, Adolfo López de Munain, Amets Sáenz
Limb-girdle muscular dystrophy type 2A (LGMD2A) is characterised by muscle wasting and progressive degeneration of proximal muscles because of mutations in the CAPN3 gene. However, the underlying pathophysiological mechanisms of muscle degeneration are still not well understood. The objective of this study was to assess the relevance of genes with differential expression in the muscle of LGMD2A patients. For this purpose, we analysed their in vitro expression in primary cultures of human myoblasts and myotubes...
March 16, 2017: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/28298922/interactions-between-ppar-gamma-and-the-canonical-wnt-beta-catenin-pathway-in-type-2-diabetes-and-colon-cancer
#11
REVIEW
Yves Lecarpentier, Victor Claes, Alexandre Vallée, Jean-Louis Hébert
In both colon cancer and type 2 diabetes, metabolic changes induced by upregulation of the Wnt/beta-catenin signaling and downregulation of peroxisome proliferator-activated receptor gamma (PPAR gamma) may help account for the frequent association of these two diseases. In both diseases, PPAR gamma is downregulated while the canonical Wnt/beta-catenin pathway is upregulated. In colon cancer, upregulation of the canonical Wnt system induces activation of pyruvate dehydrogenase kinase and deactivation of the pyruvate dehydrogenase complex...
2017: PPAR Research
https://www.readbyqxmd.com/read/28296881/transcriptomic-responses-to-environmental-temperature-by-turtles-with-temperature-dependent-and-genotypic-sex-determination-assessed-by-rnaseq-inform-the-genetic-architecture-of-embryonic-gonadal-development
#12
Srihari Radhakrishnan, Robert Literman, Jennifer Neuwald, Andrew Severin, Nicole Valenzuela
Vertebrate sexual fate is decided primarily by the individual's genotype (GSD), by the environmental temperature during development (TSD), or both. Turtles exhibit TSD and GSD, making them ideal to study the evolution of sex determination. Here we analyze temperature-specific gonadal transcriptomes (RNA-sequencing validated by qPCR) of painted turtles (Chrysemys picta TSD) before and during the thermosensitive period, and at equivalent stages in soft-shell turtles (Apalone spinifera-GSD), to test whether TSD's and GSD's transcriptional circuitry is identical but deployed differently between mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28296140/inhibitors-of-stat3-%C3%AE-catenin-and-igf-1r-sensitize%C3%A2-mouse-pik3ca%C3%A2-mutant%C3%A2-breast-cancer-to-pi3k-inhibitors
#13
Vanessa F Merino, Soonweng Cho, Xiaohui Liang, Sunju Park, Kideok Jin, Qian Chen, Duojia Pan, Cynthia A Zahnow, Alan R Rein, Saraswati Sukumar
Although mutations in the phosphoinositide 3-kinase-catalytic subunit (PIK3CA) are common in breast cancer, PI3K inhibitors alone have shown modest efficacy. We sought to identify additional pathways altered in PIK3CA mutant tumors that might be targeted in combination with PI3K inhibitors. We generated two transgenic mouse models expressing the human PIK3CA-H1047R and the -E545K hotspot mutant genes in the mammary gland and evaluated their effects on development and tumor formation. Molecular analysis identified pathways altered in these mutant tumors, which were also targeted in multiple cells lines derived from the PIK3CA tumors...
March 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28294540/traditional-chinese-medicine-bushen-jianpi-huoxue-decoction-prevents-diabetic-osteoporosis-in-rats-via-wnt-and-nuclear-factor-kappa-b-signaling-pathways
#14
Yongqing Zhang, Mingming Liu, Haisheng Li, Zetao Chen, Na Liang, Jianguo Xu, Xiaoli Zhang, Yihang Zhang
AIM: The aim of this study was to evaluate the therapeutic effect of a traditional Chinese medicine (TCM), Bushen-Jianpi-Huoxue decoction (BJHD), on diabetic osteoporosis (DOP) and the action mechanisms likely mediated by nuclear factor-kappa B (NF-κB) and Wnt signaling pathways. METHODS: Fifty-five male Wistar rats were used in this study; they were divided into normal control (n = 10) and established DOP model (n = 45) groups. The DOP model was induced using a combination high carbohydrate - high fat diet and intraperitoneal injections of streptozotocin (STZ)...
March 13, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28293627/integrating-mirna-and-mrna-expression-profiling-uncovers-mirnas-underlying-fat-deposition-in-sheep
#15
Guangxian Zhou, Xiaolong Wang, Chao Yuan, Danju Kang, Xiaochun Xu, Jiping Zhou, Rongqing Geng, Yuxin Yang, Zhaoxia Yang, Yulin Chen
MicroRNAs (miRNAs) are endogenous, noncoding RNAs that regulate various biological processes including adipogenesis and fat metabolism. Here, we adopted a deep sequencing approach to determine the identity and abundance of miRNAs involved in fat deposition in adipose tissues from fat-tailed (Kazakhstan sheep, KS) and thin-tailed (Tibetan sheep, TS) sheep breeds. By comparing HiSeq data of these two breeds, 539 miRNAs were shared in both breeds, whereas 179 and 97 miRNAs were uniquely expressed in KS and TS, respectively...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28293067/syndecan-1-acts-as-an-important-regulator-of-cxcl1-expression-and-cellular-interaction-of-human-endometrial-stromal-and-trophoblast-cells
#16
Dunja Maria Baston-Buest, Olga Altergot-Ahmad, Sarah Jean Pour, Jan-Steffen Krüssel, Udo Rudolf Markert, Tanja Natascha Fehm, Alexandra Petra Bielfeld
Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28293052/beta-catenin-forms-protein-aggregation-at-high-concentrations-in-hek293tcells
#17
Marie Saghaeian Jazi, Seyed Mahmoud Arab Najafi
BACKGROUND: The canonical Wnt signal transduction (or the Wnt/β-catenin pathway) plays a crucial role in the development of animals and in carcinogenesis. Beta-catenin is the central component of this signaling pathway. The activation of Wnt/β-catenin signaling results in the cytoplasmic and nuclear accumulation of β-catenin. In the nucleus, β-catenin interacts with the TCF/LEF transcription factors and, therefore, participates in the upregulation or downregulation of some important genes involved in diverse cellular activities...
January 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28292937/disruption-of-tcf-%C3%AE-catenin-binding-impairs-wnt-signalling-and-induces-apoptosis-in-soft-tissue-sarcoma-cells
#18
Esther Martinez-Font, Irene Felipe-Abrio, Silvia Calabuig-Fariñas, Rafael F Ramos, Josefa Terrasa, Oliver Vögler, Regina Alemany, Javier Martín-Broto, Antònia Obrador-Hevia
Soft tissue sarcomas (STS) are malignant tumours of mesenchymal origin and represent around 1% of adult cancers, being a very heterogeneous group of tumours with more than 50 different subtypes. The Wnt signalling pathway is involved in the development and in the regulation, self-renewal and differentiation of mesenchymal stem cells and plays a role in sarcomagenesis. In this study we have tested pharmacological inhibition of Wnt signalling mediated by disruption of TCF/β-catenin binding and AXIN stabilization, being the first strategy more efficient in reducing cell viability and downstream effects...
March 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28292882/cthrc1-lowers-pulmonary-collagen-associated-with-bleomycin-induced-fibrosis-and-protects-lung-function
#19
Andrew P Binks, Megyn Beyer, Ryan Miller, Renee J LeClair
Idiopathic pulmonary fibrosis (IPF) involves collagen deposition that results in a progressive decline in lung function. This process involves activation of Smad2/3 by transforming growth factor (TGF)-β and Wnt signaling pathways. Collagen Triple Helix Repeat-Containing-1 (Cthrc1) protein inhibits Smad2/3 activation. To test the hypothesis that Cthrc1 limits collagen deposition and the decline of lung function, Cthrc1 knockout (Cthrc1(-/-)) and wild-type mice (WT) received intratracheal injections of 2.5 U/kg bleomycin or saline...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28289330/the-heterogeneity-of-cancer-stem-like-cells-at-the-invasive-front
#20
Go J Yoshida
Cancer stem-like cells exhibit the multi-functional roles to survive and persist for a long period in the minimal residual disease after the conventional anti-cancer treatments. Cancer stem-like cells of solid malignant tumors which highly express CD44v8-10, the variant isoform of CD44 generated by alternative splicing, has a resistance to redox stress by the robust production of glutathione mediated by ESRP1-CD44v-xCT (cystine/glutamate antiporter) axis. It has been reported that CD44v and c-Myc tend to show the inversed expression pattern at the invasive front of the aggressive tumors...
2017: Cancer Cell International
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