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Xiao-Long Zhang, Gang Xu, Yi Zhou, Jia-Jun Yan
Renal cell carcinoma (RCC) is insensitive to conventional chemotherapy and radiotherapy, and its prognosis remains poor. Targeted therapy is a novel technique for the treatment of RCC. The present study aimed to determine the precise effects of microRNA-183 (miR-183) on RCC. Reverse transcription-quantitative polymerase chain reaction analysis was conducted in order to analyze the expression level of miR-183 in RCC cell lines. Cell transfection, viability assays and invasion assays were also performed, followed by western blot analysis and a luciferase reporter assay, in order to examine the effects of miR-183...
April 2018: Oncology Letters
Meng Wu, Mengya Chen, Yubo Ma, Jiajia Yang, Renfang Han, Yaping Yuan, Xingxing Hu, Mengmeng Wang, Xu Zhang, Shengqian Xu, Rui Liu, Guangming Jiang, Jianhua Xu, Zongwen Shuai, Yanfeng Zou, Guixia Pan, Faming Pan
BACKGROUND: Current findings regarding serum Dickkopf-1 (DKK-1) concentration in ankylosing spondylitis (AS) have proven inconsistent. This meta-analysis was performed to provide a better understanding of serum DKK-1 and AS. METHODS: Online electronic databases were used to retrieve all relevant articles published before November 2017. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. RESULTS: 23 studies, containing 1348 AS patients and 909 healthy controls, were included in this meta-analysis...
March 12, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Xiaobin Huang, Janine N Post, Leilei Zhong, Jeroen Leijten, Staffan Larsson, Marcel Karperien, André Struglics
OBJECTIVE: To explore the involvement of the WNT and BMP antagonists Dickkopf-related protein 1 (DKK1), Frizzled-related protein (FRZB) and Gremlin 1 (GREM1) in knee injury and osteoarthritis (OA). DESIGN: The antagonists were immunoassayed in synovial fluid from a cross-sectional cohort of 9 knee healthy reference subjects, patients with recent (0-77 days, n=158) or old (1-37 years, n=50) knee injuries, and OA (n=22). Cartilage (ARGS-aggrecan, cartilage oligomeric matrix protein and C2C type II collagen) and other biomarkers were assessed in synovial fluid in a subset of samples...
March 8, 2018: Osteoarthritis and Cartilage
Klara Janjić, Barbara Cvikl, Christoph Kurzmann, Andreas Moritz, Hermann Agis
BACKGROUND: To understand the responses of the dental pulp to hypoxia is of high relevance for regenerative endodontics and dental traumatology. Here, we aimed to reveal the effects of hypoxia and the hypoxia mimetic agent L-mimosine (L-MIM) on the production of sclerostin (SOST) and dickkopf-1 (DKK-1) in human dental pulp-derived cells (DPC). METHODS: DPC in monolayer, spheroid and tooth slice cultures were treated with L-MIM or hypoxia. Resazurin-based toxicity and MTT assays were performed to determine cell viability...
March 9, 2018: BMC Oral Health
Ken Kataoka, Natsumi Maehara, Yuki Ayabe, Hitoshi Murata, Nam-Ho Huh, Masakiyo Sakaguchi
Our previous studies revealed that REIC/Dkk-3 was expressed various tissues, including skin keratinocytes. The aim of the present study was to identify the factors that regulate the expression of the dickkopf Wnt signaling pathway inhibitor 3 (REIC/Dkk‑3) tumor suppressor gene in normal human skin keratinocytes (NHKs). Several growth factors and cytokines that have previously been reported to be involved in the growth and differentiation of keratinocytes were screened as potential regulators. Western blot analysis was performed using protein from NHKs cultured with/without various factors including the epidermal growth factor, tumor necrosis factor‑α, transforming growth factor‑β, interleukin (IL)‑1F9, IL‑6, IL‑8 and Ca2+...
March 5, 2018: Molecular Medicine Reports
Eva Z Hoseth, Florian Krull, Ingrid Dieset, Ragni H Mørch, Sigrun Hope, Erlend S Gardsjord, Nils Eiel Steen, Ingrid Melle, Hans-Richard Brattbakk, Vidar M Steen, Pål Aukrust, Srdjan Djurovic, Ole A Andreassen, Thor Ueland
The Wnt signaling pathway plays a crucial role in neurodevelopment and in regulating the function and structure of the adult nervous system. Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders with evidence of subtle neurodevelopmental, structural and functional neuronal abnormalities. We aimed to elucidate the role of aberrant regulation of the Wnt system in these disorders by evaluating plasma levels of secreted Wnt modulators in patients (SCZ = 551 and BD = 246) and healthy controls (HCs = 639) using enzyme immune-assay...
March 6, 2018: Translational Psychiatry
Bushra Parveen, Manjari Tripathi, Divya Vohora
Long-term anti-epileptic drug (AED) therapy compromises bone health. Though vitamin-D deficiency is proposed to be involved, it alone is not held responsible. This accounts for investigating other mechanisms in bone accrual. Recent studies have shown modulation of inhibitors of wnt pathway, sclerostin and dickkopf-1 (DKK-1), in glucocorticoids-induced osteoporosis. We investigated whether AED monotherapy modulates wnt inhibitors in Indian women with epilepsy. Women of age > 20-40 years with the diagnosis of epilepsy and receiving AEDs (carbamazepine, valproate and levetiracetam) for at least a year were enrolled...
March 5, 2018: Basic & Clinical Pharmacology & Toxicology
Z Malik, M Alexiou, B Hallgrimsson, A N Economides, H U Luder, D Graf
Formation of highly organized dental hard tissues is a complex process involving sequential and ordered deposition of an extracellular scaffold, followed by its mineralization. Odontoblast and ameloblast differentiation involves reciprocal and sequential epithelial-mesenchymal interactions. Similar to early tooth development, various Bmps are expressed during this process, although their functions have not been explored in detail. Here, we investigated the role of odontoblast-derived Bmp2 for tooth mineralization using Bmp2 conditional knockout mice...
February 1, 2018: Journal of Dental Research
Lubomir Bodnar, Rafał Stec, Szczepan Cierniak, Agnieszka Synowiec, Gabriel Wcisło, Marzena Jesiotr, Robert Koktysz, Paweł Chrom, Cezary Szczylik
BACKGROUND: The aim of the present study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of the WNT/β-catenin pathway. PATIENTS AND METHODS: In a prospective, single-arm, phase II study, patients with mRCC received everolimus (10 mg/d) in a 30-day cycle. We performed a prospectively planned evaluation of the potential biomarkers of the WNT/β-catenin pathway...
February 2, 2018: Clinical Genitourinary Cancer
Juhura G Almazi, Peter Pockney, Craig Gedye, Nathan D Smith, Hubert Hondermarck, Nicole M Verrills, Matthew D Dun
BACKGROUND: Optimized blood collection tubes (BCT) have been developed to expand the utility of plasma cell free DNA (cfDNA) and are in clinical use. The appropriateness of plasma collected and stored in these tubes for proteomic analysis is unknown. METHODS: Paired blood samples were collected in BCT and traditional K3EDTA (EDTA) tubes from healthy controls, and from colorectal cancer patients (CRC) before and after surgery, and stored for between 45 minutes and 48 hours at room temperature...
February 24, 2018: Proteomics. Clinical Applications
Michael K Dame, Durga Attili, Shannon D McClintock, Priya H Dedhia, Peter Ouillette, Olaf Hardt, Alana M Chin, Xiang Xue, Julie Laliberte, Erica L Katz, Gina M Newsome, David R Hill, Alyssa J Miller, Yu-Hwai Tsai, David Agorku, Christopher H Altheim, Andreas Bosio, Becky Simon, Linda C Samuelson, Jay A Stoerker, Henry D Appelman, James Varani, Max S Wicha, Dean E Brenner, Yatrik M Shah, Jason R Spence, Justin A Colacino
The intestine is maintained by stem cells located at the base of crypts and distinguished by the expression of LGR5. Genetically engineered mouse models have provided a wealth of information about intestinal stem cells, while less is known about human intestinal stem cells due to difficulty detecting and isolating these cells. We established an organoid repository from patient-derived adenomas, adenocarcinomas, and normal colon, which we analyzed for variants in 71 colorectal cancer (CRC) associated genes. Normal and neoplastic colon tissue organoids were analyzed by immunohistochemistry and fluorescent-activated cell sorting for LGR5...
February 21, 2018: Development
Francesca Maria Trovato, Paola Castrogiovanni, Marta Anna Szychlinska, Francesco Purrello, Giuseppe Musumeci
BACKGROUND: The metabolic syndrome is associated with sarcopenia. Decreased serum levels of Vitamin D (VitD) and insulin-like growth factor (IGF)-1 and their mutual relationship were also reported. We aimed to evaluate whether different dietary profiles, containing or not VitD, may exert different effects on muscle molecular morphology. METHODS: Twenty-eight male rats were fed for 10 weeks in order to detect early defects induced by different dietary regimens: regular diet (R); regular diet with vitamin D supplementation (R-DS) and regular diet with vitamin D restriction (R-DR); high-fat butter-based diets (HFB-DS and HFB-DR) with 41% energy from fat; high-fat extra-virgin olive oil-based diets (HFEVO-DS and HFEVO-DR) with 41% energy from fat...
February 17, 2018: Nutrients
Jieping Li, Wenlin Gong, Xiaoxue Li, Ruirong Wan, Fengzhen Mo, Zhenghua Zhang, Panpan Huang, Zixi Hu, Zongqiang Lai, Xiaoling Lu, Yongxiang Zhao
Hepatocellular carcinoma (HCC) is one of the most common cancers around the world. Multiple etiologic factors such as virus and environment can lead to HCC. It is a challenge for us to successfully detect early HCC due to the lack of effective characterized and specific biomarkers. However, if the early diagnosis is successfully realized, it provides crucial chance for HCC patients to receive effective treatment as early as possible. Dickkopf-1 (DKK-1) is a secretary glycoprotein, which negatively regulates Wnt pathway through binding to surface receptors LRP5/6 and Kremen 1/2...
August 1, 2018: Journal of Nanoscience and Nanotechnology
Ryan D Ross, Raj C Shah, Sue Leurgans, Teodoro Bottligieri, Robert S Wilson, D Rick Sumner
Background: Osteoporosis and Alzheimer's disease (AD) are common diseases of aging that would seem to be unrelated, but may be linked through the influence of bone-derived signals on brain function. The current study aimed to investigate the relationship between circulating levels of bone-related biomarkers and cognition. Methods: The population included 103 community-dwelling older individuals with memory concerns but without cognitive impairment. A global cognition summary measure was collected at baseline and 6, 12, and 18-months post-enrollment by converting raw scores from 19 cognitive function tests to z-scores and averaging...
February 8, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical 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
Roelof A J Smit, Johan Wouter Jukema, Iris Postmus, Ian Ford, Pieternella Eline Slagboom, Bastiaan T Heijmans, Saskia Le Cessie, Stella Trompet
In recent years, visit-to-visit variability of serum lipids has been linked to both clinical outcomes and surrogate markers for vascular disease. In this article, we present an overview of the current evidence connecting this intraindividual variability to these outcome measures, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest. In addition, we undertook an explorative genome-wide association analysis on visit-to-visit variability of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, examining additive effects in 2530 participants from the placebo arm of the PROspective Study of Pravastatin in the Elderly at Risk trial...
January 11, 2018: Journal of Clinical Lipidology
Ting-Ting Liu, Yang Wu, Ting Niu
Dickkopf-1 (DKK1) is an ideal target for the immunotherapy of multiple myeloma. Heat Shock protein70 (HSP70) is a class of important molecular chaperone to promote antigen presentation. Homologous xenogeneic antigens can enhance immunogenicity and induce stronger anti-tumor immune response than that of allogeneic ones. Therefore, we constructed human DKK1 and human HSP70 DNA fusion vaccine (hDKK1-hHSP70), and then determined its anti-tumor immuno- genicity and anti-tumor effects on immunizing BALB/c mice already inoculated with NS-1 murine multiple myeloma cells in prophylactic and therapeutic models using cytotoxic T lymphocytes, enzyme-lined immunosorbent assay, flow cytometry, immunohistochemistry and Hochest staining...
January 2, 2018: Oncotarget
Jadwiga Ambroszkiewicz, Magdalena Chełchowska, Katarzyna Szamotulska, Grażyna Rowicka, Witold Klemarczyk, Małgorzata Strucińska, Joanna Gajewska
Vegetarian diets contain many beneficial properties as well as carry a risk of inadequate intakes of several nutrients important to bone health. The aim of the study was to evaluate serum levels of bone metabolism markers and to analyze the relationships between biochemical bone markers and anthropometric parameters in children on vegetarian and omnivorous diets. The study included 70 prepubertal children on a lacto-ovo-vegetarian diet and 60 omnivorous children. Body composition, bone mineral content (BMC), and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry...
February 7, 2018: Nutrients
Sepanta Hosseinpour, Maryam Rezai Rad, Arash Khojasteh, Homa Zadeh
BACKGROUND: Currently, antibodies are progressively applied in medicine for different purposes from diagnosis to treatments. Over twenty monoclonal antibodies utilized for many therapeutic reasons from therapy of cancers, immune disorders, and osteoporosis to localized bony defects. In addition, therapeutic antibodies represented various findings in bone tissue engineering. OBJECTIVES: The current study aims to systematically review the available literature on antibody assisted bone regeneration in animal models...
February 6, 2018: Current Stem Cell Research & Therapy
Argyrios Sklavos, Theofilos Poutahidis, Alexander Giakoustidis, Kali Makedou, Katerina Angelopoulou, Alexander Hardas, Paola Andreani, Argyro Zacharioudaki, George Saridis, Thomas Goulopoulos, Kalliopi Tsarea, Maria Karamperi, Vassilios Papadopoulos, Vassilios Papanikolaou, Apostolos Papalois, Stavros Iliadis, Satvinder Mudan, Daniel Azoulay, Dimitrios Giakoustidis
Recent evidence has suggested that downregulation of the Wnt/β-catenin signaling pathway may contribute to the development and growth of HCC. Consequently, elements of this pathway have begun to emerge as potential targets for improving outcomes of anti-HCC. Thus, the present study sought to examine the effects of Wnt-1 blockade using the classical diethylnitrosamine (DEN)-induced chemical carcinogenesis mouse model of HCC. The depletion of Wnt-1 using neutralizing antisera was done for ten consecutive days at the age of 9 months and mice were examined for the following 20 days...
January 2018: Oncology Letters
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