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RANK ligand

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https://www.readbyqxmd.com/read/28100627/inflammatory-biomarkers-predict-heart-failure-severity-and-prognosis-in-patients-with-heart-failure-with-preserved-ejection-fraction-a-holistic-proteomic-approach
#1
Camilla Hage, Erik Michaëlsson, Cecilia Linde, Erwan Donal, Jean-Claude Daubert, Li-Ming Gan, Lars H Lund
BACKGROUND: Underlying mechanisms in heart failure (HF) with preserved ejection fraction remain unknown. We investigated cardiovascular plasma biomarkers in HF with preserved ejection fraction and their correlation to diastolic dysfunction, functional class, pathophysiological processes, and prognosis. METHODS AND RESULTS: In 86 stable patients with HF and EF ≥45% in the Karolinska Rennes (KaRen) biomarker substudy, biomarkers were quantified by a multiplex immunoassay...
February 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28096962/extra-virgin-olive-oil-in-maternal-diet-increases-osteogenic-genes-expression-but-high-amounts-have-deleterious-effects-on-bones-in-mice-offspring-at-adolescence
#2
Seyedeh Neda Mousavi, Fariba Koohdani, Mohamadreza Baghaban Eslaminejad, Pantea Izadi, Mohamadreza Eshraghian, Forough Azam Sayahpour, Leila Shafiei Neek, Farzad Shidfar
OBJECTIVES: Maternal high-fat diet has been shown to have deleterious effects on the offspring bones. However, there is no study to assess the effects of type and amount of maternal dietary oil in an isocaloric diet, with focus on extra virgin olive oil (EVOO). The objective of the current study was to test the hypothesis that type of maternal dietary oil has more effects than its amount in an isocaloric diet during gestation and lactation on bone genes expression in offspring in adolescence...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28080056/metadynamics-simulations-distinguish-short-and-long-residence-time-inhibitors-of-cyclin-dependent-kinase-8
#3
Donatella Callegari, Alessio Lodola, Daniele Pala, Silvia Rivara, Marco Mor, Andrea Rizzi, Anna Maria Capelli
The duration of drug efficacy in vivo is a key aspect primarily addressed during the lead optimization phase of drug discovery. Hence, the availability of robust computational approaches that can predict the residence time of a compound at its target would accelerate candidate selection. Nowadays the theoretical prediction of this parameter is still very challenging. Starting from methods reported in the literature, we set up and validated a new metadynamics (META-D)-based protocol that was used to rank the experimental residence times of 10 arylpyrazole cyclin-dependent kinase 8 (CDK8) inhibitors for which target-bound X-ray structures are available...
January 12, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28075460/roles-of-oncogenes-and-tumor-suppressor-genes-in-osteoclastogenesis-review
#4
Akari Minami, Mako Ogino, Noriko Nakano, Mayuko Ichimura, Atsuko Nakanishi, Toshiyuki Murai, Yasuko Kitagishi, Satoru Matsuda
Osteoporosis is a bone disease that poses a tremendous burden to health care. The receptor activator of nuclear factor-κB (RANK) and its ligand (RANKL) have been a major focus of this research field. RANKL signaling not only activates a variety of downstream signaling pathways required for osteoclast development, but crosstalk with other signaling pathways also adjusts bone homeostasis both in normal physiology and in bone disease. Consequently, novel drugs specifically targeting RANK-RANKL and their signaling pathways in osteoclasts are expected to revolutionize the treatment of various bone diseases such as osteoporosis...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28070039/-effects-of-laser-solid-forming-of-porous-titanium-on-proliferation-of-osteoblast-and-rankl-opg-expression
#5
Hui Chen, Shanshan Du, Ping Zhen, Xusheng Li, Xiaoyan Liang, Lijuan Fan, Jie Jiang, Haiou Yang, Jun Liu
To evaluate the effect of laser solid forming (LSF) of porous titanium on receptor activator of NF-κB ligand (RANKL)/osteoprorotegerin (OPG) expression and osteoblast cells growth.
 Methods: The DMEM and sterile saline were used for porous titanium extract. The osteoblast cells were cultured in the extract while equal amount of  DMEM and sterile saline were added to the control group. The growth of the cells were observed under an inverted phase contrast microscope. MTT was used to detect the growth inhibitory rates...
December 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28065384/the-effects-of-fat-induced-obesity-on-bone-metabolism-in-rats
#6
Wei Li, Peng Xu, Cuizhe Wang, Xiaodan Ha, Yajuan Gu, Yan Wang, Jun Zhang, Jianxin Xie
OBJECTIVE: The aim of the current study was to investigate the effects of obesity, induced via a high-fat diet, on bone metabolism in rats. METHODS: Two hundred healthy Wistar male rats aged 4 weeks were fed a standard diet and a high-fat diet. At specific time points (week 0, 4, 6, 8, and 10), plasma was collected to determine the levels of glucose and lipid metabolism. Additionally, enzyme-linked immunoassays were performed to determine the plasma levels of adipocyte and bone metabolism factors...
January 3, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28064107/ethnomedicine-based-evaluation-of-osteoprotective-properties-of-tinospora-cordifolia-on-in-vitro-and-in-vivo-model-systems
#7
G Abiramasundari, C M Mohan Gowda, G Pampapathi, Sheela Praveen, S Shivamurugan, M Vijaykumar, A Devi, M Sreepriya
Indian ethnomedicine acclaims the use of Tinospora cordifolia (TC) in the treatment of bone fractures and vat rakta (gout). The objective of the study is to investigate the effects of alcoholic extract of Tinospora cordifolia on bone remodeling (involving osteoblastic and osteoclastic actions) in vitro and protect against ovariectomy-induced bone loss in vivo. Human osteoblast-like cells MG-63 and primary osteoblast cells isolated from rat femur were used as osteoblast models and RAW macrophage cell line 264...
January 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28059045/computational-screening-of-ccr5-inhibitors-as-potential-entry-inhibitor-microbicides-using-3d-qsar-studies-docking-and-molecular-dynamics-simulation
#8
Radhika Ramachandran, Muthusankar Aathi, D Durairaj Ruban, Shanmughavel Piramanyagam
BACKGROUND: The chemokine receptor CCR5 acts as a co-receptor for HIV binding and it is considered as an important target by CCR5 antagonists. Entry inhibitor based microbicides gain much importance nowadays as these drugs act at an early stage of HIV lifecycle and thus hinder the viral replication process in humans. The present study intends to identify a CCR5 antagonist which could be developed as a microbicide using computational approaches. METHOD: The pharmacophore modeling and 3D QSAR studies was used to identify CCR5 antagonists with enhanced antagonist activity...
January 6, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28054270/breaking-from-tradition-establishing-more-realistic-sediment-quality-guidelines
#9
G Allen Burton
Sediment quality guidelines vary wildly across nations. The approaches to derive these guidelines range from crude percentile rankings of total concentrations of single chemicals to theoretical approaches that are driven by biological available effect levels. This results in a range of orders of magnitude for "safe" or threshold levels by chemical. Even the more scientifically advanced approaches using theoretical approaches are problematic in that they do not consider chemical mixtures, alternate routes of exposure, and other ligands that limit bioavailability...
January 4, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28032980/ligand-discovery-for-a-peptide-binding-gpcr-by-structure-based-screening-of-fragment-and-lead-like-chemical-libraries
#10
Anirudh Ranganathan, Philipp Heine, Axel Rudling, Andreas Plückthun, Lutz Kummer, Jens Carlsson
Peptide-recognizing G protein-coupled receptors (GPCRs) are promising therapeutic targets, but often resist drug discovery efforts. Determination of crystal structures for peptide-binding GPCRs has provided opportunities to explore structure-based methods in lead development. Molecular docking screens of two chemical libraries, containing either fragment- or lead-like compounds, against a Neurotensin receptor 1 crystal structure allowed for a comparison between different drug development strategies for peptide-binding GPCRs...
December 29, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/28025385/prognostic-value-of-bone-and-vascular-derived-molecular-biomarkers-in-hemodialysis-and-renal-transplant-patients-a-systematic-review-and-meta-analysis
#11
Gernot Pichler, Maria C Haller, Alexander Kainz, Myles Wolf, Josep Redon, Rainer Oberbauer
BACKGROUND: Patients undergoing hemodialysis and kidney graft recipients are high-risk populations for cardiovascular and all-cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin (OPN), Klotho protein and bone morphogenetic protein-7 (BMP-7) are bone- and vascular-derived molecular biomarkers that have been shown to be associated with cardiovascular surrogate end points; however, currently available data on the prognostic value of these biomarkers is inconsistent...
December 26, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28004300/effect-of-wenhua-juanbi-recipe-on-expression-of-receptor-activator-of-nuclear-factor-kappa-b-ligand-osteoprotegerin-and-tumor-necrosis-factor-receptor-superfamily-member-14-in-rats-with-collagen-induced-arthritis
#12
Xi-de Liu, Yun-Qing Wang, Long Cai, Li-Hong Ye, Fang Wang, Ying-Ying Feng
OBJECTIVE: To study the effect of Wenhua Juanbi Recipe (, WJR) on expression of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor receptor superfamily member 14 (TNFRSF14, also known as LIGHT) in rats with collagen-induced arthritis (CIA). METHODS: CIA rats were generated by subcutaneous injection of bovine collagen type-II at the tail base. Sixty CIA rats were randomly assigned (10 animals/group) to: model, methotrexate (MTX)-treated (0...
December 21, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28002811/aberrant-regulation-of-rankl-opg-in-women-at-high-risk-of-developing-breast-cancer
#13
Stefan Kiechl, Daniel Schramek, Martin Widschwendter, Evangelia-Ourania Fourkala, Alexey Zaikin, Allison Jones, Bernadette Jaeger, Brigitte Rack, Wolfgang Janni, Christoph Scholz, Johann Willeit, Siegfried Weger, Agnes Mayr, Andrew Teschendorff, Adam Rosenthal, Lindsay Fraser, Susan Philpott, Louis Dubeau, Mohammed Keshtgar, Rebecca Roylance, Ian J Jacobs, Usha Menon, Georg Schett, Josef M Penninger
Breast cancer is the most common female cancer, affecting approximately one in eight women during their lifetime in North America and Europe. Receptor Activator of NF-kB Ligand (RANKL), its receptor RANK and the natural antagonist osteoprotegerin (OPG) are essential regulators of bone resorption. We have initially shown that RANKL/RANK are essential for hormone-driven mammary epithelial proliferation in pregnancy and RANKL/RANK have been implicated in mammary stem cell biology. Using genetic mouse-models, we and others identified the RANKL/RANK system as a key regulator of sex hormone, BRCA1-mutation, and oncogene-driven breast cancer and we proposed that RANKL/RANK might be involved in the initiation of breast tumors...
December 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/28000877/low%C3%A2-molecular-weight-fucoidan-inhibits-the-differentiation-of-osteoclasts-and-reduces-osteoporosis-in-ovariectomized-rats
#14
Xin Jin, Liguo Zhu, Xiulan Li, Jian Jia, Yang Zhang, Xiaolei Sun, Jianxiong Ma, Zhaojie Liu, Xinlong Ma
Fucoidan is a type of sulfated polysaccharide isolated from seaweed. The present study used ovariectomized Sprague‑Dawley rats, which were treated with fucoidan. The effects of fucoidan on bone metabolism, density and microarchitecture were assessed using micro‑computed tomography (CT), histomorphometric analysis, biochemical markers of bone metabolism (Serum procollagen type I N propeptide and C‑terminal telopeptide‑1) and tests of mechanical competence of the femur. In addition, the effects of low‑molecular weight fucoidan (LMWF) on in vitro cultured osteoclasts were examined, in order to determine the mechanisms underlying LMWF‑induced osteoclastic inhibition...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27988276/high-throughput-quantitative-analysis-of-human-osteoclast-differentiation-and-activity
#15
Natalie A Diepenhorst, Cameron J Nowell, Patricia Rueda, Kim Henriksen, Tracie Pierce, Anna E Cook, Philippe Pastoureau, Massimo Sabatini, William N Charman, Arthur Christopoulos, Roger J Summers, Patrick M Sexton, Christopher J Langmead
Osteoclasts are multinuclear cells that degrade bone under both physiological and pathophysiological conditions. Osteoclasts are therefore a major target of osteoporosis therapeutics aimed at preserving bone. Consequently, analytical methods for osteoclast activity are useful for the development of novel biomarkers and/or pharmacological agents for the treatment of osteoporosis. The nucleation state of an osteoclast is indicative of its maturation and activity. To date, activity is routinely measured at the population level with only approximate consideration of the nucleation state (an 'osteoclast population' is typically defined as cells with ≥3 nuclei)...
February 15, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/27981900/pharmacophore-and-docking-guided-virtual-screening-study-for-discovery-of-type-i-inhibitors-of-vegfr-2-kinase
#16
Heena R Bhojwani, Urmila J Joshi
BACKGROUND: Kinase domain of VEGFR-2 displays conformational flexibility which leads to existence of two kinds of inhibitors viz. type I and type II inhibitors. They exhibit different binding modes and this necessitates the development of separate pharmacophore models for them. METHODS: The virtual screening study for discovery of type I inhibitors of VEGFR-2 kinase was done by using combined pharmacophore (generated using PHASE and validated by 3D-QSAR) and docking (Glide) based approach...
December 14, 2016: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/27981421/identification-of-binding-mode-and-prospective-structural-features-of-novel-nef-protein-inhibitors-as-potential-anti-hiv-drugs
#17
Suri Moonsamy, Soumendranath Bhakat, Muthusamy Ramesh, Mahmoud E S Soliman
Human immunodeficiency virus (HIV)-negative factor (Nef) protein is an accessory pathogenic factor, which plays a significant role in acquired immune deficiency syndrome (AIDS). Nef deficient HIV virus took a longer time to progress into AIDS. Therefore, targeting Nef protein is considered as a key strategy towards HIV/AIDS treatment. Up-to-date, only few compounds were reported as Nef inhibitors. This has prompted us to provide a first account of an integrated computational framework in order to identify more potential Nef inhibitors...
December 16, 2016: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27975655/a-water-extract-of-malva-verticillata-seeds-suppresses-osteoclastogenesis-and-bone-resorption-stimulated-by-rank-ligand
#18
K S Shim, C J Lee, J Y Ma
No abstract text is available yet for this article.
December 2016: Planta Medica
https://www.readbyqxmd.com/read/27941684/structural-determinants-of-alkyne-reactivity-in-copper-catalyzed-azide-alkyne-cycloadditions
#19
Xiaoguang Zhang, Peiye Liu, Lei Zhu
This work represents our initial effort in identifying azide/alkyne pairs for optimal reactivity in copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. In previous works, we have identified chelating azides, in particular 2-picolyl azide, as "privileged" azide substrates with high CuAAC reactivity. In the current work, two types of alkynes are shown to undergo rapid CuAAC reactions under both copper(II)- (via an induction period) and copper(I)-catalyzed conditions. The first type of the alkynes bears relatively acidic ethynyl C-H bonds, while the second type contains an N-(triazolylmethyl)propargylic moiety that produces a self-accelerating effect...
December 9, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27937122/rational-screening-of-peroxisome-proliferator-activated-receptor-%C3%AE-agonists-from-natural-products-potential-therapeutics-for-heart-failure
#20
Rui Chen, Jing Wan, Jing Song, Yan Qian, Yong Liu, Shuiming Gu
CONTEXT: Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Activation of PPARγ pathway has been shown to enhance fatty acid oxidation, improve endothelial cell function, and decrease myocardial fibrosis in heart failure. Thus, the protein has been raised as an attractive target for heart failure therapy. OBJECTIVE: This work attempted to discover new and potent PPARγ agonists from natural products using a synthetic strategy of computer virtual screening and transactivation reporter assay...
December 2017: Pharmaceutical Biology
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