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Yonglin Yu, Xinkun Shen, Zhong Luo, Yan Hu, Menghuan Li, Pingping Ma, Qichun Ran, Liangliang Dai, Ye He, Kaiyong Cai
Oxidative stress is commonly existed in bone degenerative disease (osteoarthritis, osteoporosis etc.) and some antioxidants had great potential to enhance osteogenesis. In this study, we aim to investigate the anti-oxidative properties of various TiO2 nanotubes (TNTs) so to screen the desirable size for improved osteogenesis and reveal the underlying molecular mechanism in vitro. Comparing cellular behaviors under normal and oxidative stress conditions, an interesting conclusion was obtained. In normal microenvironment, small TNTs were beneficial for adhesion and proliferation of osteoblasts, but large TNTs greatly increased osteogenic differentiation...
March 13, 2018: Biomaterials
Rivka Sukenik Halevy, Huan-Chieh Chien, Bo Heinz, Michael J Bamshad, Deborah A Nickerson, Martin Kircher, Nadav Ahituv
Isolated hand syndactyly is a common limb malformation with limited known genetic etiology. We used exome sequencing to discover two novel variants, chr11 g.46896373C>G; p.D1403H and chr11 g.46893078G>T; p.Q1564K, in LRP4 in a child with isolated bilateral syndactyly of the third and fourth fingers. Each variant was inherited from a different parent and neither parent was affected. Variants in LRP4 have been previously associated with syndactyly in Cenani-Lenz syndactyly syndrome and Sclerosteosis 2, but have not been reported in individuals with isolated syndactyly...
March 10, 2018: Human Mutation
Mirta Basha, Bénédicte Demeer, Nicole Revencu, Raphael Helaers, Stephanie Theys, Sami Bou Saba, Odile Boute, Bernard Devauchelle, Geneviève Francois, Bénédicte Bayet, Miikka Vikkula
BACKGROUND: Oral clefts, that is, clefts of the lip and/or cleft palate (CL/P), are the most common craniofacial birth defects with an approximate incidence of ~1/700. To date, physicians stratify patients with oral clefts into either syndromic CL/P (syCL/P) or non-syndromic CL/P (nsCL/P) depending on whether the CL/P is associated with another anomaly or not. In general, patients with syCL/P follow Mendelian inheritance, while those with nsCL/P have a complex aetiology and, as such, do not adhere to Mendelian inheritance...
March 2, 2018: Journal of Medical Genetics
Regina Cheuk-Lam Lo, Carmen Oi-Ning Leung, Kristy Kwan-Shuen Chan, Daniel Wai-Hung Ho, Chun-Ming Wong, Terence Kin-Wah Lee, Irene Oi-Lin Ng
Identification and characterization of functional molecular targets conferring stemness properties in hepatocellular carcinoma (HCC) offers crucial insights to overcome the major hurdles of tumor recurrence, metastasis and chemoresistance in clinical management. In the current study, we investigated the significance of Cripto-1 in contributing to HCC stemness. Cripto-1 was upregulated in the sorafenib-resistant clones derived from HCC cell lines and patient-derived xenograft that we previously developed, suggesting an association between Cripto-1 and stemness...
February 14, 2018: Cell Death and Differentiation
Shubin Yu, Zhongyuan Wang, Zijie Su, Jiaxing Song, Liang Zhou, Qi Sun, Shanshan Liu, Shiyue Li, Ying Li, Meina Wang, Guo-Qiang Zhang, Xue Zhang, Zhong-Jian Liu, Desheng Lu
BACKGROUND: Gigantol is a bibenzyl compound derived from several medicinal orchids. This biologically active compound has been shown to have promising therapeutic potential against cancer cells, but its mechanism of action remains unclear. METHODS: The inhibitory effect of gigantol on Wnt/β-catenin signaling was evaluated with the SuperTOPFlash reporter system. The levels of phosphorylated low-density lipoprotein receptor related protein 6 (LRP6), total LRP6 and cytosolic β-catenin were determined by Western blot analysis...
February 14, 2018: BMC Complementary and Alternative Medicine
Lei Li, Jipeng Wan, Jing Xue, Hongyan Li, Shan Wang, Qian Zhou, Yu Zhou, Xietong Wang
Remodeling of maternal spiral artery after the implantation of embryo relies on tightly regulated trophoblast functions and is pivotal to ensure the success of pregnancy. Low-density lipoprotein receptor-related protein 6 (LRP6) is implicated in angiogenesis and several vascular diseases, but its function in trophoblast regulation is still not fully understood. We aimed to investigate the involvement of LRP6 in trophoblast functions during maternal spiral artery remodeling. HTR-8/SVneo cells, a trophoblast cell line, were employed to examine the impact of LRP6 knockdown on proliferation, apoptosis, and migration, as well as invasion and tube formation...
January 1, 2018: Reproductive Sciences
Qian Xiao, Jibo Wu, Wei-Jia Wang, Shiyang Chen, Yingxia Zheng, Xiaoqing Yu, Katrina Meeth, Mahnaz Sahraei, Alfred L M Bothwell, Lieping Chen, Marcus Bosenberg, Jianfeng Chen, Veronika Sexl, Le Sun, Lin Li, Wenwen Tang, Dianqing Wu
Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion...
February 12, 2018: Nature Medicine
Wen-Chien Huang, Kuang-Tai Kuo, Bamodu Oluwaseun Adebayo, Chun-Hua Wang, Yu-Jen Chen, Ketao Jin, Tung-Hu Tsai, Chi-Tai Yeh
Innate or acquired drug resistance and consequent tumor relapse in lung cancer patients have been linked to activities of cancer stem cells (CSCs). Therefore, targeting CSCs is suggested as an effective approach for non-small cell lung cancer (NSCLC) therapy. In this study, we demonstrated that garcinol, a polyisoprenylated benzophenone isolated from fruiting bodies of Garcinia indica, and possessing anti-inflammatory, antioxidant, acetyltransferase inhibitory, and anticancer activities, modulates activities of lung CSCs (LCSCs) and their associated aggressiveness...
December 27, 2017: Journal of Nutritional Biochemistry
Martin Pellicelli, Hadla Hariri, Julie A Miller, René St-Arnaud
In the nucleus of differentiated osteoblasts, the alpha chain of nascent polypeptide associated complex (αNAC) interacts with cJUN transcription factors to regulate the expression of target genes, including Osteocalcin (Bglap2). PTH induces the phosphorylation of αNAC on serine 99 through a Gαs-PKA dependent pathway. This leads to activation of αNAC and expression of Bglap2. To identify additional target genes regulated by PTH-activated αNAC, we performed ChIP-Seq against αNAC in PTH-treated MC3T3-E1 cells...
January 27, 2018: Biochimica et Biophysica Acta
Ofelia Tacchelly-Benites, Zhenghan Wang, Eungi Yang, Hassina Benchabane, Ai Tian, Michael P Randall, Yashi Ahmed
The aberrant activation of Wnt signal transduction initiates the development of 90% of colorectal cancers, the majority of which arise from inactivation of the tumor suppressor Adenomatous polyposis coli (APC). In the classical model for Wnt signaling, the primary role of APC is to act, together with the concentration-limiting scaffold protein Axin, in a "destruction complex" that directs the phosphorylation and consequent proteasomal degradation of the transcriptional activator β-catenin, thereby preventing signaling in the Wnt-off state...
February 2018: PLoS Genetics
Xing Yang, Lei Wang, Qiang Wang, Lexiang Li, Yao Fu, Junying Sun
Recent studies have demonstrated that microRNA-183 (miR-183) deregulates and plays major roles in many tumors. However, the role of miR-183 in osteosarcoma (OS) pathogenesis is still largely unknown. In this study, we first over-expressed and knocked down miR-183 in MG63 and U20S cells, respectively. Functional analyses showed that ectopic expression of miR-183 suppressed MG63 cell growth, migration, and invasion in vitro and in vivo, whereas knockdown of endogenous miR-183 in U20S cells significantly enhanced these abilities...
January 31, 2018: Biochemical and Biophysical Research Communications
Yea Eun Kang, Jin-Man Kim, Koon Soon Kim, Joon Young Chang, Mingyu Jung, Junguee Lee, Shinae Yi, Hyeon Woo Kim, Jung Tae Kim, Kyungmin Lee, Min Jeong Choi, Seul Ki Kang, Seong Eun Lee, Hyon-Seung Yi, Bon Seok Koo, Minho Shong
The signaling pathway involving the R-spondins and its cognate receptor, GPR48/LGR4, is crucial in development and carcinogenesis. However, the functional implications of the R-spondin-GPR48/LGR4 pathway in thyroid remain to be identified. The aim of this study was to investigate the role of R-spondin-GPR48/LGR4 signaling in papillary thyroid carcinomas. We retrospectively reviewed a total of 214 patients who underwent total thyroidectomy and cervical lymph node dissection for papillary thyroid carcinoma. The role of GPR48/LGR4 in proliferation and migration was examined in thyroid cancer cell lines...
December 29, 2017: Oncotarget
Kejia Li, Xiaochao Zhang, Bo He, Renhua Yang, Yue Zhang, Zhiqiang Shen, Peng Chen, Wei Du
Geraniin is an ellagitannin isolated from Phyllanthus amarus and has a wide range of bioactivities. Our previous study demonstrated that geraniin could alleviate osteoporosis by accelerating bone formation, but the mechanism remains unclear. This study aimed to elucidate the molecular mechanisms by which geraniin promotes osteoblast proliferation and differentiation in vitro. Primary rat bone marrow-derived mesenchymal stem cells were separated and divided into sham operated (Sham) group, Sham treated with geraniin (Sham + GE) group, ovariectomized (OVX) group, OVX treated with geraniin (OVX + GE) group, OVX treated with osteogenic medium (OVX + OM) group, OVX treated with Wnt inhibitor (OVX + WI) group, and OVX treated with Wnt inhibitor and geraniin (OVX + W I + GE) group...
January 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zhidan Chen, Yang Li, Ying Wang, Juying Qian, Hong Ma, Xiang Wang, Guoliang Jiang, Ming Liu, Yanpeng An, Leilei Ma, Le Kang, Jianguo Jia, Chunjie Yang, Guoping Zhang, Ying Chen, Wei Gao, Mingqiang Fu, Zheyong Huang, Huiru Tang, Yichun Zhu, Junbo Ge, Hui Gong, Yunzeng Zou
Low density lipoprotein receptor-related protein 6 (LRP6), a wnt co-receptor, regulates multiple functions in various organs. However, the roles of LRP6 in the adult heart are not well understood. Methods: We observed LRP6 expression in heart with end-stage dilated cardiomyopathy (DCM) by western blot. Tamoxifen-inducible cardiac-specific LRP6 knockout mouse was constructed. Hemodynamic and echocardiographic analyses were performed to these mice. Results: Cardiac LRP6 expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to control group...
2018: Theranostics
Haibin Wang, Guoxing Xu, Zhengjie Huang, Weizheng Li, Huali Cai, Yunda Zhang, Disheng Xiong, Gang Liu, Shengjie Wang, Zengfu Xue, Qi Luo
NLRP6, a member of the Nod-like receptor family, protects against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms involved in this NLRP6-mediated protection remain unclear. Here, we show that NLRP6 was down-regulated in approximately 75% of primary gastric cancer cases and exhibited significant associations with advanced clinical-stage lymph node metastasis and poor overall survival. Functional studies established that ectopic overexpression or down-regulation of NLRP6 inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase via P21 and Cyclin D1 both in vitro and in vivo...
December 19, 2017: Oncotarget
Nam-Kyung Lee, Yafeng Zhang, Yang Su, Scott Bidlingmaier, Daniel W Sherbenou, Kevin D Ha, Bin Liu
Cell signaling pathways are often shared between normal and diseased cells. How to achieve cell type-specific, potent inhibition of signaling pathways is a major challenge with implications for therapeutic development. Using the Wnt/β-catenin signaling pathway as a model system, we report here a novel and generally applicable method to achieve cell type-selective signaling blockade. We constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the effector antigen) and a cell type-associated antigen (the guide antigen) that provides the targeting specificity...
January 15, 2018: Scientific Reports
Qian Yao, Yu An, Wei Hou, Ya-Nan Cao, Meng-Fei Yao, Ning-Ning Ma, Lin Hou, Hong Zhang, Hai-Jing Liu, Bo Zhang
Low density lipoprotein (LDL) receptor-related protein-6 (LRP6) is an important co-receptor of Wnt pathway, which plays a predominant role in development and progression of colorectal cancer. Recently, dysregulation of LRP6 has proved to be involved in the progression of cancers, but its biological role and clinical significance in colorectal cancer remain unclear. In present study, we revealed that phosphorylation of LRP6 was aberrantly upregulated in colorectal carcinoma correlating with TNM or Dukes staging and worse prognosis...
December 12, 2017: Oncotarget
Yong-Kang Zhang, Jing-Ming Li, Li Qin
AIM: To investigate whether curcumin suppressed corneal neovascularization (CNV) formation via inhibiting activation of Wnt/β-catenin pathway. METHODS: Suture-induced CNV was established on Sprague-Dawley (SD) rats. Curcumin were daily administrated by subconjunctival injection. Phosphorylation of low-density lipoprotein receptor-related protein 6 (LRP6) and nuclear accumulation of β-catenin, two indicators of activated Wnt/β-catenin pathway, were determined by Western-blot analysis in subconfluent/proliferating human microvascular endothelial cells (HMEC) and neovascularized corneas...
2017: International Journal of Ophthalmology
Hui-Ling Huang, Ya-Lan Zhang, Wen-Fa Chen, Chun-Ling Wu
To explore the effects and mechanism of aqueous extracts of gecko on cancer stem cells properties of hepatocellular carcinoma. In vitro, MTT assay was used to detect the cells growth in Huh7 and Hep3B. Spheroid-forming assay and flow cytometry were performed to observe the the stemness of Huh7 and Hep3B cells. The protein expressions of β-catenin, CD44, c-Myc, CCND1, Sox2, Oct4, Nanog and ABCG2 were detected by Western blot. Interacting proteins were detected by co-immunoprecipitation; and a subcutaneous xenograft model was used to detect the stemness of hepatoma carcinoma cells...
October 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Caiqi Ma, Chuanghua Luo, Haofan Yin, Yang Zhang, Wenjun Xiong, Ting Zhang, Tianxiao Gao, Xi Wang, Di Che, Zhenzhen Fang, Lei Li, Jinye Xie, Mao Huang, Liuqing Zhu, Ping Jiang, Weiwei Qi, Ti Zhou, Zhonghan Yang, Wei Wang, Jianxing Ma, Guoquan Gao, Xia Yang
BACKGROUND: Tumor-induced lymphangiogenesis and lymphatic metastasis are predominant during the metastasis of many types of cancers. However, the endogenous inhibitors that counterbalance the lymphangiogenesis and lymphatic metastasis of tumors have not been well evaluated. Kallistatin has been recognized as an endogenous angiogenesis inhibitor. METHODS AND RESULTS: Our recent study showed for the first time that the lymphatic vessel density (LVD) was reduced in lung and stomach sections from kallistatin-overexpressing transgenic mice...
December 14, 2017: Gastric Cancer
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