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Priscila E Kobayashi, Carlos E Fonseca-Alves, Luis G Rivera-Calderón, Márcio Carvalho, Hellen Kuasne, Silvia R Rogatto, Renée Laufer-Amorim
Prostate cancer is a heterogeneous disease with high levels of clinical and gene heterogeneity, consequently offering several targets for therapy. Dogs with naturally occurring prostate cancer are useful models for molecular investigations and studying new treatment efficacy. Three genes and proteins associated with the WNT pathway (β-catenin, APC and E-cadherin) and Caveolin-1 (CAV-1) were evaluated in canine pre-neoplastic proliferative inflammatory atrophy (PIA), prostate cancer and metastatic disease. The APC gene methylation status was also investigated...
March 5, 2018: Research in Veterinary Science
Siqi Huang, Jing Chen, Ruicheng Tian, Jing Wang, Chenjie Xie, Hongxiang Gao, Yuhua Shan, Jie Hong, Zhen Zhang, Min Xu, Song Gu
BACKGROUND: Hepatoblastoma (HB) is the most common liver cancer found in early childhood. These patients suffer poor outcomes and need novel therapies. An abnormal activation of Wnt signaling is the hallmark of HB tumorigenesis, and its pathway is a potential candidate for a pharmacological intervention. PROCEDURE: Tissue samples of patients with HB were collected for RNA-seq, quantitative real-time PCR, and immunohistochemistry to identify if disheveled-2 (Dvl-2) was a target gene...
March 12, 2018: Pediatric Blood & Cancer
Shirley Abitbol, Rajae Dahmani, Cédric Coulouarn, Bruno Ragazzon, Bernhard Mlecnik, Nadia Senni, Mathilde Savall, Pascale Bossard, Pierre Sohier, Valerie Drouet, Emilie Tournier, Florent Dumont, Romain Sanson, Julien Calderaro, Jessica Zucman-Rossi, Mireille Vasseur-Cognet, Pierre-Alexandre Just, Benoît Terris, Christine Perret, Hélène Gilgenkrantz
BACKGROUND & AIMS: The Wnt/β-catenin pathway is the most frequently deregulated pathway in hepatocellular carcinoma (HCC). Inactivating mutations of the gene encoding AXIN1, a known negative regulator of the Wnt/β-catenin signaling pathway, are observed in about 10% of HCCs. Whole-genome studies usually place HCC with AXIN1 mutations and CTNNB1 mutations in the group of tumors with Wnt/β-catenin activated program. However, it has been shown that HCCs with activating CTNNB1 mutations form a group of HCCs, with a different histology, prognosis and genomic signature to those with inactivating biallelic AXIN1 mutations...
March 7, 2018: Journal of Hepatology
Zhiming Shan, Na An, Jielin Qin, Junmei Yang, Hongqi Sun, Wei Yang
Substantial evidence has demonstrated the involvement of long non-coding RNAs (lncRNAs) in the development and progression of colorectal cancer (CRC) via their regulation on cancer cell proliferation, apoptosis, invasion and metastasis pathways. The current study aimed to understand the role of lncRNA Linc00675 in the progression and metastasis of CRC and to identify the potential lncRNA-miRNA interactions and signaling pathways underlying the mechanisms of action of Linc00675 in CRC. Our data firstly demonstrated the down-regulation of Linc00675 in both CRC cells and clinical CRC tissues...
March 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Gui Pan, Haojie Hao, Jianping Liu
The transplantation of insulin-producing cells (IPCs) or pancreatic progenitor cells is a theoretical therapy for diabetes with insulin insufficiency. Isolated hepatocytes from newborn rats (within 24 h after birth) were progressively induced into IPCs using 5-aza-2'-deoxycytidine, Trichostatin A, retinoic acid, insulin-transferrin-selenium, and nicotinamide. We transplanted Pdx1+ pancreatic progenitors into STZ-induced diabetic mice and found the decreased blood glucose and increased insulin level in comparison with diabetic model...
March 7, 2018: Biochemical and Biophysical Research Communications
Wenjie Deng, Yueyuan Wang, Shuo Zhao, Yujie Zhang, Yan Chen, Xuyang Zhao, Lei Liu, Shixiu Sun, Lin Zhang, Bixing Ye, Jun Du
Molecule interacting with CasL 1 (MICAL1) is a multidomain flavoprotein mono-oxygenase that strongly involves in cytoskeleton dynamics and cell oxidoreduction metabolism. Recently, results from our laboratory have shown that MICAL1 modulates reactive oxygen species (ROS) production, and the latter then activates phosphatidyl inositol 3-kinase (PI3K)/protein kinase B (Akt) signalling pathway which regulates breast cancer cell invasion. Herein, we performed this study to assess the involvement of MICAL1 in breast cancer cell proliferation and to explore the potential molecular mechanism...
March 10, 2018: Journal of Cellular and Molecular Medicine
Matthias Vonbrüll, Elisabeth Riegel, Christian Halter, Michaela Aigner, Holger Bock, Birgit Werner, Thomas Lindhorst, Thomas Czerny
There have been many attempts to unveil the therapeutic potential of antisense molecules during the last decade. Due to its specific role in canonical Wnt signalling, β-catenin is a potential target for an antisense-based antitumour therapy. In order to establish such a strategy with peptide nucleic acids, we developed a reporter assay for quantification of antisense effects. The luciferase-based assay detects splice blocking with high sensitivity. Using this assay, we show that the splice donor of exon 13 of β-catenin is particularly suitable for an antisense strategy, as it results in a truncated protein which lacks transactivating functions...
March 9, 2018: Molecular Biotechnology
J Cai, W Li, T Sun, X Li, E Luo, D Jing
The effects of exogenous pulsed electromagnetic field (PEMF) stimulation on T1DM-associated osteopathy were investigated in alloxan-treated rabbits. We found that PEMF improved bone architecture, mechanical properties, and porous titanium (pTi) osseointegration by promoting bone anabolism through a canonical Wnt/β-catenin signaling-associated mechanism, and revealed the clinical potential of PEMF stimulation for the treatment of T1DM-associated bone complications. INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with deteriorated bone architecture and impaired osseous healing potential; nonetheless, effective methods for resisting T1DM-associated osteopenia/osteoporosis and promoting bone defect/fracture healing are still lacking...
March 9, 2018: Osteoporosis International
Banjun Ruan, Zheng Zhu, Zhao Yan, Wei Yang, Dongsheng Zhai, Li Wang, Zichen Ye, Huanyu Lu, An Xiang, Jingwei Liang, Yinghao Jiang, Chengming Xu, Zhenyu Wang, Ming Wei, Xiaoying Lei, Xiaorui Cao, Zifan Lu
BACKGROUND: The reciprocal fate decision of mesenchymal stem cells (MSCs) to either bone or adipocytes is determined by Wnt-related signaling and the glucagon-like peptide-1 receptor (GLP-1R). Azoramide, an ER stress alleviator, was reported to have an antidiabetic effect. In this study, we investigated the function of azoramide in regulating the lineage determination of MSCs for either adipogenic or osteogenic differentiation. METHODS: In this study, microcomputed tomography and histological analysis on bone morphogenetic protein (BMP)2-induced parietal periosteum bone formation assays, C3H10T1/2 and mouse bone marrow MSC-derived bone formation and adipogenesis assays, and specific staining for bone tissue and lipid droplets were used to evaluate the role of azoramide on the lineage determination of MSC differentiation...
March 9, 2018: Stem Cell Research & Therapy
Klaske J Schippers, Scott A Nichols
β-catenin acts as a transcriptional co-activator in the Wnt/β-catenin signaling pathway and a cytoplasmic effector in cadherin-based cell adhesion. These functions are ancient within animals, but the earliest steps in β-catenin evolution remain unresolved due to limited data from key lineages - sponges, ctenophores and placozoans. Previous studies in sponges have characterized β-catenin expression dynamics and used GSK3B antagonists to ectopically activate the Wnt/β-catenin pathway; both approaches rely upon untested assumptions about the conservation of β-catenin function and regulation in sponges...
March 7, 2018: Molecular Biology and Evolution
Zhi-Fang Deng, Hui-Ling Zheng, Jian-Guo Chen, Yi Luo, Jun-Feng Xu, Gang Zhao, Jia-Jing Lu, Hou-Hong Li, Shuang-Qi Gao, Deng-Zheng Zhang, Ling-Qiang Zhu, Yong-Hui Zhang, Fang Wang
β-Catenin has been implicated in major depressive disorder (MDD), which is associated with synaptic plasticity and dendritic arborization. MicroRNAs (miRNA) are small noncoding RNAs containing about 22 nucleotides and involved in a variety of physiological and pathophysiological process, but their roles in MDD remain largely unknown. Here, we investigated the expression and function of miRNAs in the mouse model of chronic social defeat stress (CSDS). The regulation of β-catenin by selected miRNA was validated by silico prediction, target gene luciferase reporter assay, and transfection experiment in neurons...
March 7, 2018: Cerebral Cortex
Alice Giuliodori, Giorgia Beffagna, Giulia Marchetto, Chiara Fornetto, Francesco Vanzi, Stefano Toppo, Nicola Facchinello, Mattia Santimaria, Andrea Vettori, Stefania Rizzo, Mila Della Barbera, Kalliopi Pilichou, Francesco Argenton, Gaetano Thiene, Natascia Tiso, Cristina Basso
Aims: Arrhythmogenic cardiomyopathy (AC) is an inherited heart disease characterized by life-threatening ventricular arrhythmias and fibro-fatty replacement of the myocardium. More than 60% of AC patients show pathogenic mutations in genes encoding for desmosomal proteins. By focusing our attention on the AC8 form, linked to the junctional protein Desmoplakin (DSP), we present here a zebrafish model of DSP deficiency, exploited to identify early changes of cell signalling in the cardiac region...
March 7, 2018: Cardiovascular Research
Xiaobin Wang, Mingxiang Zou, Jing Li, Bing Wang, Qianshi Zhang, Fubin Liu, Guohua Lü
Intervertebral disc (IVD) degeneration (IDD) is a major contributor to low back pain. During IDD progression, ROS can be produced in the form of H2 O2 in nucleus pulposus cells (NPCs) in response to elevated cytokines, leading to subsequent alternations of cell fate and metabolic processes. Genetic factors are considered as main contributors to IDD pathopoiesis. Herein, we investigated the detailed function and mechanism of H19, one of the most up-regulated lncRNAs in IDD specimens, in H2 O2 -induced cell senescence model in NPCs...
March 9, 2018: Journal of Cellular Biochemistry
Atika Resti Fitri, Prasit Pavasant, Supakarn Chamni, Piyamas Sumrejkanchanakij
BACKGROUND: Asiaticoside is a compound isolated from Herb Centella asiatica, which has been shown to promote osteogenic differentiation of human periodontal ligament (hPDL) cells. This study investigated the molecular mechanism underlying the asiaticoside-induced osteogenic differentiation of hPDL cells. METHODS: hPDL cells were incubated with various concentrations of asiaticoside to test cell viability by MTT assay. The mRNA expression levels were analyzed by using quantitative real-time polymerase chain reaction (PCR)...
February 22, 2018: Journal of Periodontology
Jaichandran Sivalingam, Hong Yu Chen, Bin-Xia Yang, Zhong Ri Lim, Alan Tin Lun Lam, Tsung Liang Woo, Allen Kuan-Liang Chen, Shaul Reuveny, Yuin-Han Loh, Steve Kah-Weng Oh
No abstract text is available yet for this article.
March 8, 2018: Haematologica
Morgan Preziosi, Minakshi Poddar, Sucha Singh, Satdarshan P Monga
Activation of the Wnt/β-catenin signaling is reported in large subsets of hepatocellular carcinoma (HCC). Upregulationof Wnt genes is one contributing mechanism. In the current study, we sought to address the role of hepatocyte-derived Wnts in a model of hepatic injury, fibrosis and carcinogenesis. We subjected hepatocyte-specific Wntless knockout mice (HP-KO), unable to secrete Wnts from hepatocytes, and littermate controls (HP-CON), to diethylnitrosamine and carbon tetrachloride (DEN/CCl4) and harvested at 3, 5, and 6 months for histological and molecular analysis...
March 8, 2018: Gene Expression
Xuelian Li, GuoYuan Wang, MuGe QiLi, HaiHai Liang, TianShi Li, XiaoQiang E, Ying Feng, Ying Zhang, Xiao Liu, Ming Qian, BoZhi Xu, ZhiHang Shen, Samuel Chege Gitau, DanDan Zhao, HongLi Shan
BACKGROUND/AIMS: Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload-induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment...
March 2, 2018: Cellular Physiology and Biochemistry
Bingling Dai, Tianfeng Yang, Yujiao Ma, Nan Ma, Xianpeng Shi, Dongdong Zhang, Jie Zhang, Yanmin Zhang
Looking for novel, effective and less toxic therapies for cervical cancer is of significant importance. In this study, we reported that HMQ-T-F2(F2) significantly inhibited cell proliferation and transplantable tumour growth. Mechanistically, HMQ-T-F2 inhibited HeLa cell growth through repressing the expression and nuclear translocation of β-catenin, enhancing Axin expression, as well as downregulating the Wnt downstream targeted proteins. Knock-down of a checkpoint β-catenin by siRNA significantly attenuated HeLa cell proliferation...
March 7, 2018: Journal of Cellular and Molecular Medicine
Sobha Puppala, Cun Li, Jeremy P Glenn, Romil Saxena, Samer Gawrieh, Amy Quinn, Jennifer Palarczyk, Edward J Dick, Peter W Nathanielsz, Laura A Cox
Maternal obesity (MO) increases offspring cardiometabolic disease risk. Altered fetal liver development in response to the challenge of MO has metabolic consequences underlying adverse offspring life-course health outcomes. Little is known about molecular pathways and potential epigenetic changes regulating primate fetal liver responses to MO. We hypothesized that MO would induce fetal baboon liver epigenetic changes resulting in dysregulation of key metabolic pathways that impact lipid metabolism. MO was induced prior to pregnancy by a high fat, high sucrose diet...
March 7, 2018: Journal of Physiology
Xi Xu, Yunfeng Wang, Hong Deng, Chungang Liu, Jingjing Wu, Maode Lai
Drug resistance is one of the main hurdles to overcome for the improvement of cancer patient survival. However, the underlying mechanisms remain largely unknown, and therapeutic options are limited. Here, we demonstrate a strong correlation between HMGA2 expression and chemosensitivity to 5-fluorouracil (5-FU), a widely used first-line systemic chemotherapy regimen for colorectal cancer (CRC) patients. Overexpression of HMGA2 enhances chemoresistance to 5-FU of CRC both in vitro and in vivo . Further experiments indicate that HMGA2 directly binds to the promoter of Dvl2 and induces its transcription, which leads to increased activation of the Wnt/β-catenin pathway...
February 9, 2018: Oncotarget
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