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Nasser Ghaly Yousif, Najah R Hadi, Alaa Manea Hassan
OBJECTIVE: To investigate the mechanistic pathway of both indocyanine green (ICG)-001 in attenuated endotoxemia-induced cardiac depression through downregulation cardiac Wnt/ β-catenin cell signaling. MATERIALS AND METHODS: Adult (4-6 months) male Albino-Webster mice, their weights ranged from 25 to 30 g, were pretreated with ICG-001 i.p., following cecal ligation and puncture (CLP). Left ventricle (LV) function was assessed using a microcatheter system. Monocyte chemoattractant protein-1 (MCP-1) and cytokines mediators in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay...
January 2017: Journal of Pharmacology & Pharmacotherapeutics
Dario F Riascos-Bernal, Prameladevi Chinnasamy, Jordana N Gross, Vanessa Almonte, Lander Egaña-Gorroño, Dippal Parikh, Smitha Jayakumar, Liang Guo, Nicholas E S Sibinga
OBJECTIVE: Smooth muscle cells (SMCs) contribute to neointima formation after vascular injury. Although β-catenin expression is induced after injury, whether its function is essential in SMCs for neointimal growth is unknown. Moreover, although inhibitors of β-catenin have been developed, their effects on SMC growth have not been tested. We assessed the requirement for SMC β-catenin in short-term vascular homeostasis and in response to arterial injury and investigated the effects of β-catenin inhibitors on vascular SMC growth...
March 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Shuiyu Ji, Hao Deng, Wei Jin, Pengpeng Yan, Rending Wang, Lisha Pang, Jingyi Zhou, Jiaming Zhang, Xiaoying Chen, Xiang Zhao, Jia Shen
Long-term exposure to peritoneal dialysate with high glucose (HG) leads to peritoneal fibrosis and thus decreases dialysis efficiency. In this study, we explored the role of β-catenin in this process. C57BL/6 mice received daily intraperitoneal injection with 10% of the body weight of saline (control), 4.25% glucose peritoneal dialysis fluid (PDF), or PDF combined with 5 mg·kg(-1) of the β-catenin inhibitor ICG-001 (PDF+ICG) for 30 days. Also, mice peritoneal epithelial cells (mPECs) were cultured in 4.25% glucose (HG) or combined with 10 μm ICG-001 (HG+ICG) for 48 h...
February 2017: FEBS Open Bio
Zichuan Ping, Xuanyang Hu, Liangliang Wang, Jiawei Shi, Yunxia Tao, Xiexing Wu, Zhenyang Hou, Xiaobin Guo, Wen Zhang, Huilin Yang, Yaozeng Xu, Zhirong Wang, Dechun Geng
Wear debris-induced inhibition of bone regeneration and extensive bone resorption were common features in peri-prosthetic osteolysis (PPO). Here, we investigated the effect of melatonin on titanium particle-stimulated osteolysis in a murine calvariae model and mouse-mesenchymal-stem cells (mMSCs) culture system. Melatonin inhibited titanium particle-induced osteolysis and increased bone formation at osteolytic sites, confirmed by radiological and histomorphometric data. Furthermore, osteoclast numbers decreased dramatically in the low- and high-melatonin administration mice, as respectively, compared with the untreated animals...
January 11, 2017: Acta Biomaterialia
Yong Zhang, Yu-Lin Wen, Ji-Wei Ma, Jie-Cheng Ye, Xiao Wang, Jian-Xian Huang, Chao-Yue Meng, Xiao-Ze Xu, Shao-Xiang Wang, Xue-Yun Zhong
Cancer stem cells (CSCs) in glioma are often responsible for relapse and resistance to therapy. The purpose of the present study was to confirm the self-renewal and migration inhibitory effects of tetrandrine (Tet), which is a compound extracted from the dried root of Stephania tetrandra S. Moore, toward glioma stem-like cells (GSLCs) and to examine the associated molecular mechanisms. Using a neurosphere culture technique, we enriched the GSLC population from the human glioblastoma cell lines U87 and U251...
January 2017: International Journal of Oncology
Hongrui Wang, Yake Meng, Quanjun Cui, Fujun Qin, Haisong Yang, Yu Chen, Yajun Cheng, Jiangang Shi, Yongfei Guo
Mounting evidence indicates that microRNAs (miRNAs) are involved in multiple processes of osteogenic differentiation. MicroRNA-101 (miR-101), identified as a tumor suppressor, has been implicated in the pathogenesis of several types of cancer. However, the expression of miR-101 and its roles in the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) remain unclear. We found that the miR-101 expression level was significantly increased during the osteogenic differentiation of hBMSCs...
November 15, 2016: Scientific Reports
Aftab Taiyab, Anna Korol, Paula A Deschamps, Judith A West-Mays
Purpose: Transforming growth factor-β-induced epithelial-mesenchymal transition (EMT) is one of the main causes of posterior capsular opacification (PCO) or secondary cataract; however, the signaling events involved in TGF-β-induced PCO have not been fully characterized. Here, we focus on examining the role of β-catenin/cyclic AMP response element-binding protein (CREB)-binding protein (CBP) and β-catenin/T-cell factor (TCF)-dependent signaling in regulating cytoskeletal dynamics during TGF-β-induced EMT in lens epithelial explants...
October 1, 2016: Investigative Ophthalmology & Visual Science
Zhe Huang, Yong Feng
Cancer cell-derived exosomes have been actively released into the tumor microenvironment with pleiotropic roles in tumor growth and metastasis, including angiogenesis and immune modulation. However, the functions and underlying mechanisms of exosomes shed by colorectal cancer (CRC) cells under hypoxic conditions remains unknown. Here, we found that exosomes derived from hypoxic CRC cells promoted the proliferation and migration of endothelial cells. Suppression of exosome secretion through RAB27a knockdown in CRC cells inhibited exosomal induced proliferation and migration of endothelial cells...
October 5, 2016: Oncology Research
Anne Tr Noll, Thorsten Cramer, Steven Wm Olde Damink, Frank G Schaap
Cholangiocarcinoma (CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells...
September 18, 2016: World Journal of Hepatology
Tim Koopmans, Stijn Crutzen, Mark H Menzen, Andrew J Halayko, Tillie-Louise Hackett, Darryl A Knight, Reinoud Gosens
BACKGROUND AND PURPOSE: Asthma is a heterogeneous chronic inflammatory disease, characterized by the development of structural changes (airway remodelling). β-catenin, a transcriptional co-activator is fundamentally involved in airway smooth muscle growth, and may be a potential target in the treatment of airway smooth muscle remodelling. EXPERIMENTAL APPROACH: Using small-molecule compounds that selectively target β-catenin breakdown or its interactions with transcriptional co-activators, we assessed their ability to inhibit airway smooth muscle remodelling in vitro and in vivo...
September 15, 2016: British Journal of Pharmacology
L Yao, H Zhao, H Tang, J Xiong, W Zhao, L Liu, H Dong, F Zou, S Cai
BACKGROUND: Aberrant activation of β-catenin signaling by both WNT-dependent and WNT-independent pathways has been demonstrated in asthmatic airways, which is thought to contribute critically in remodeling of the airways. Yet, the exact role of β-catenin in asthma is very poorly defined. As we have previously reported abnormal expression of β-catenin in a toluene diisocyanate (TDI)-induced asthma model, in this study, we evaluated the therapeutic efficacy of two small molecules XAV-939 and ICG-001 in TDI-asthmatic male BALB/c mice, which selectively block β-catenin-mediated transcription...
September 14, 2016: Allergy
Kyung-Il Kim, Do-Sun Jeong, Eui Chang Jung, Jeung-Hoon Lee, Chang Deok Kim, Tae-Jin Yoon
BACKGROUND: Wnt/β-catenin signaling is important in development and differentiation of melanocytes. OBJECTIVE: The object of this study was to evaluate the effects of several Wnt/β-catenin signaling inhibitors on pigmentation using melanoma cells. METHODS: Melanoma cells were treated with Wnt/β-catenin signaling inhibitors, and then melanin content and tyrosinase activity were checked. RESULTS: Although some inhibitors showed slight inhibition of pigmentation, we failed to observe potential inhibitory effect of those chemicals on pigmentation of HM3KO melanoma cells...
November 2016: Journal of Dermatological Science
Hsiao-Hui Lin, Wen-Chi Feng, Li-Chun Lu, Yu-Yun Shao, Chih-Hung Hsu, Ann-Lii Cheng
Sorafenib, a multikinase inhibitor, is currently the only approved drug for advanced hepatocellular carcinoma (HCC). The current study tested the hypothesis whether inhibition of the Wnt/β-catenin signaling pathway could improve the anti-tumor effects of sorafenib in HCC. ICG-001, a small molecule which blocks the interaction of β-catenin with its transcriptional coactivator CBP, dose-dependently enhanced the growth-suppressive and apoptosis-induction effects of sorafenib in multiple HCC cell lines. Downregulation of β-catenin by RNA interference increased sorafenib sensitivity, whereas overexpression of β-catenin reduced sorafenib sensitivity in Huh7 cells...
October 10, 2016: Cancer Letters
Hye Sung Won, Kyung Mee Lee, Ju Eon Oh, Eun Mi Nam, Kyoung Eun Lee
BACKGROUND: The β-catenin signaling is important in cell growth and differentiation and is frequently dysregulated in various cancers. The most well-known mechanism of endocrine resistance is cross-talk between the estrogen receptor (ER) and other growth factor signaling, such as phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathway. In the present study, we investigated whether β-catenin could be a potential target to overcome endocrine resistance in breast cancer...
2016: PloS One
Michael Bordonaro, Darina Lazarova Lazarova
BACKGROUND: The Wnt signaling pathway, mediated through active beta-catenin, is responsible for initiating the majority of cases of human colorectal cancer (CRC), and we have previously shown that hyperactivation of this pathway by histone deacetylase inhibitors (HDACis), such as butyrate, can induce the death of CRC cells. An important cellular switch that mediates the effects of Wnt-signaling activation is variation in the association between beta-catenin and the transcriptional coactivators cAMP response element binding (CREB) binding protein (CBP) and p300...
2016: JMIR Research Protocols
Przemyslaw Blyszczuk, Björn Müller-Edenborn, Tomas Valenta, Elena Osto, Mara Stellato, Silvia Behnke, Katharina Glatz, Konrad Basler, Thomas F Lüscher, Oliver Distler, Urs Eriksson, Gabriela Kania
AIMS: Myocardial fibrosis critically contributes to cardiac dysfunction in inflammatory dilated cardiomyopathy (iDCM). Activation of transforming growth factor-β (TGF-β) signalling is a key-step in promoting tissue remodelling and fibrosis in iDCM. Downstream mechanisms controlling these processes, remain elusive. METHODS AND RESULTS: Experimental autoimmune myocarditis (EAM) was induced in BALB/c mice with heart-specific antigen and adjuvant. Using heart-inflammatory precursors, as well as mouse and human cardiac fibroblasts, we demonstrated rapid secretion of Wnt proteins and activation of Wnt/β-catenin pathway in response to TGF-β signalling...
April 20, 2016: European Heart Journal
Jian Wang, Zhi-Hong Yang, Hua Chen, Hua-Hui Li, Li-Yong Chen, Zhu Zhu, Ying Zou, Cong-Cong Ding, Jing Yang, Zhi-Wei He
BACKGROUND: Nurr1, a member of the orphan receptor family, plays an important role in several types of cancer. Our previous work demonstrated that increased expression of Nurr1 plays a significant role in the initiation and progression of prostate cancer (PCa), though the mechanisms for regulation of Nurr1 expression remain unknown. In this study, we investigated the hypothesis that Nemo-like kinase (NLK) is a key regulator of Nurr1 expression in PCa. METHODS: Immunohistochemistry and Western blot analysis were used to evaluate levels of NLK and Nurr1 in prostatic tissues and cell lines...
March 31, 2016: BMC Cancer
Junhua Wang, Yunxia Tao, Zichuan Ping, Wen Zhang, Xuanyang Hu, Yijun Wang, Liangliang Wang, Jiawei Shi, Xiexing Wu, Huilin Yang, Yaozeng Xu, Dechun Geng
Wear-debris-induced periprosthetic osteolysis (PIO) is a common clinical condition following total joint arthroplasty, which can cause implant instability and failure. The host response to wear debris promotes bone resorption and impairs bone formation. We previously demonstrated that icariin suppressed wear-debris-induced osteoclastogenesis and attenuated particle-induced osteolysis in vivo. Whether icariin promotes bone formation in a wear-debris-induced osteolytic site remains unclear. Here, we demonstrated that icariin significantly attenuated titanium-particle inhibition of osteogenic differentiation of mesenchymal stem cells (MSCs)...
March 31, 2016: Scientific Reports
Xiaomu Guan, Mingang Xu, Sarah E Millar, John D Bartlett
Beta-catenin is a multifunctional protein that plays key roles in cadherin-based cell adherens junctions and in the Wnt signaling pathway. The canonical Wnt/β-catenin pathway can regulate transcription factors that control cell movement/invasion. We investigated whether β-catenin regulates ameloblast movement through canonical Wnt signaling. The morphological and physical properties of enamel were assessed in enamel from control and β-catenin conditional knockout (cKO) mice. Ameloblast-lineage cells (ALC) were used to investigate the potential roles of β-catenin in cell migration and in E-cadherin expression...
June 2016: European Journal of Oral Sciences
Lili Zhou, Youhua Liu
PURPOSE OF REVIEW: Intrarenal activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of hypertension and chronic kidney diseases (CKD). However, how RAS genes are regulated in vivo was poorly understood until recently. This review focuses on recent findings of the transcriptional regulation of RAS components, as well as their implication in developing novel strategies to treat the patients with CKD. RECENT FINDINGS: Bioinformatics analyses have uncovered the presence of putative binding sites for T-cell factor/β-catenin in the promoter region of all RAS genes...
March 2016: Current Opinion in Nephrology and Hypertension
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