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RANK ligand

Min Liu, Weiwei Liu, Chunyan Qiao, Bing Han
RATIONALE: Gorham-Stout disease (GSD) is characterized by aggressive bone resorption, proliferation of vascular or lymphatic vessels, and soft-tissue swelling. Bones that initially appear normal start to resorb, partially or completely. However, the etiology of GSD is unknown. PATIENT CONCERNS: A 29-year-old man with a chief complaint of toothache and mobility in the lower right mandible for the previous 1 year. DIAGNOSES: Gorham-Stout disease (GSD)...
October 2017: Medicine (Baltimore)
Jin Hee Park, Na Kyung Lee, Soo Young Lee
Osteoclasts are bone-resorbing cells that are derived from hematopoietic precursor cells and require macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL) for their survival, proliferation, differentiation, and activation. The binding of RANKL to its receptor RANK triggers osteoclast precursors to differentiate into osteoclasts. This process depends on RANKL-RANK signaling, which is temporally regulated by various adaptor proteins and kinases. Here we summarize the current understanding of the mechanisms that regulate RANK signaling during osteoclastogenesis...
October 17, 2017: Molecules and Cells
Himesh Makala, Venkatasubramanian Ulaganathan
Human mitotic kinesins are potential anticancer drug targets because of their essential role in mitotic cell division. The kinesin Eg5 (Kinesin-5, kif11) has gained much attention in this regard and has many inhibitors in different phases of clinical trials. All drug candidates considered for Eg5 so far binds to the binding site (Site 1) formed by the loop L5, helices α2 and α3 and are uncompetitive to ATP/ADP. Recently, it has been reported that Eg5 also has a second binding site (Site 2) formed by helices α4 and α6...
October 17, 2017: Journal of Receptor and Signal Transduction Research
Linda Johansson, Lisbeth Ärlestig, Heidi Kokkonen, Mikael Brink, Solbritt Rantapää-Dahlqvist
Objectives: RANK ligand (RANKL) is involved in destruction and osteoporosis in RA. In this study, the relationships between RANKL and ACPA, anti-carbamylated protein antibodies (anti-CarP), cytokines and chemokines were analysed in individuals before the onset of RA symptoms, and their associations with radiological findings at disease onset were assessed. Methods: This was a case-control study performed within the Medical Biobank of Northern Sweden that included 470 pre-symptomatic individuals [334 women and 136 men; mean (s...
September 25, 2017: Rheumatology
Johan Gabrielsson, Lambertus A Peletier, Stephan Hjorth
Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure...
October 9, 2017: Pharmacology & Therapeutics
Yu-Han Meng, Wen-Jie Zhou, Li-Ping Jin, Li-Bing Liu, Kai-Kai Chang, Jie Mei, Hui Li, Jian Wang, Da-Jin Li, Ming-Qing Li
Decidual macrophages (dMϕ) contribute to maternal-fetal tolerance. However, the mechanism of dMϕ differentiation during pregnancy is still largely unknown. Here, we report that receptor activator for nuclear factor-κ B ligand (RANKL), secreted by human embryonic trophoblasts and maternal decidual stromal cells (DSCs), polarizes dMϕ toward a M2 phenotype. This polarization is mediated through activation of Akt/signal transducer and activator of transcription 6 (STAT6) signaling, which is associated with the upregulation of histone H3 lysine-27 demethylase Jmjd3 and IRF4 in dMϕ...
October 12, 2017: Cell Death & Disease
Chao Zhang, Fang-Yuan Chang, Wen-Ya Zhou, Ji-Long Yang
BACKGROUND: Recent studies indicate that C-X-C motif chemokine receptor 4 (CXCR4) and its ligand, C-X-C motif chemokine ligand 12 (CXCL12), stimulate expression of the cell cycle regulatory protein Cyclin D1 in neurofibromatosis 1-associated malignant peripheral nerve sheath tumor (MPNST) cells and promote their proliferation. In this study, we measured the expression of CXCR4, CXCL12, and Cyclin D1 proteins in sporadic MPNST tissues from Chinese patients and investigated their prognostic values...
October 11, 2017: Chinese Journal of Cancer
Hideto Yuasa, Youhei Mantani, Natsumi Masuda, Miho Nishida, Masaya Arai, Toshifumi Yokoyama, Hiroki Tsuruta, Junichi Kawano, Nobuhiko Hoshi, Hiroshi Kitagawa
The mechanism by which indigenous bacteria on the follicle-associated epithelium (FAE) of lymphatic follicles (LFs) accelerate the differentiation of microvillous columnar epithelial cells (MV) into M-cells was immunohistochemically investigated in rat Peyer's patches. The results showed that the number of Toll-like receptor (TLR) -4(+) M-cells was greater in the FAE with expansion of bacterial colonies (LFs with bacterial colonies on the FAE: b-LF) than the FAE without expansion of bacterial colonies (nb-LF)...
October 8, 2017: Journal of Veterinary Medical Science
Ryota Sato, Takuma Shibata, Yu Tanaka, Chiharu Kato, Kiyoshi Yamaguchi, Yoichi Furukawa, Eigo Shimizu, Rui Yamaguchi, Seiya Imoto, Satoru Miyano, Kensuke Miyake
The Toll family of receptors sense microbial products and activate a defense response. The molecular machinery required for the Toll-like receptor (TLR) response is not yet fully understood. In the present study, we used a CRISPR/CAS9 screening system to study TLR responses. We employed a cell line expressing TLR with an NF-κB-driven GFP reporter. The cell line was transduced with a guide RNA library and stimulated with TLR ligands. The cells impaired in GFP induction were sorted, and gRNAs were sequenced...
July 28, 2017: International Immunology
Anusha Bitra, B Jhansi Rani, Sanket S Agarkar, Anuj S Parihar, Gopinath P Vynath, Shekhar Grover
BACKGROUND: Orthodontic treatment is one of the commonly used dental treatments. Orthodontic forces act on the bone by modulating the biomolecules, chiefly the osteoprotegerin (OPG), osteopontin (OPN), receptor activator of nuclear factor kappa-B (RANK), and RANK ligand (RANKL) (OPG ligand). Hormonal changes are known to cause marked alteration in the levels of these biomolecules. Hence, we planned this study to evaluate the response of bone biomarkers in the gingival crevicular fluid (GCF) in postmenopausal women undergoing fixed orthodontic therapy...
October 1, 2017: Journal of Contemporary Dental Practice
Ying-Duo Gao, Yuan Hu, Alejandro Crespo, Deping Wang, Kira A Armacost, James I Fells, Xavier Fradera, Hongwu Wang, Huijun Wang, Brad Sherborne, Andreas Verras, Zhengwei Peng
The 2016 D3R Grand Challenge 2 includes both pose and affinity or ranking predictions. This article is focused exclusively on affinity predictions submitted to the D3R challenge from a collaborative effort of the modeling and informatics group. Our submissions include ranking of 102 ligands covering 4 different chemotypes against the FXR ligand binding domain structure, and the relative binding affinity predictions of the two designated free energy subsets of 15 and 18 compounds. Using all the complex structures prepared in the same way allowed us to cover many types of workflows and compare their performances effectively...
October 6, 2017: Journal of Computer-aided Molecular Design
Yunmei Huang, Yu Lin, Yinsheng Wu, Jianwei Zeng, Meiya Huang, Shiming Guo, Wenjuan Luo, Haiming Lin, Yanping Lin
Postmenopausal osteoporosis (PMOP) is characterized by increased bone loss due to enhanced osteoclastogenesis and bone resorption. A Chinese herbal formula, jiangugranule (JG), exhibited great efficacy in the clinical treatment of PMOP. However, the molecular mechanisms underlying the therapeutic effects remain unclear. The present study aimed to examine the effects of JG‑containing serum on receptor activator of nuclear factor‑κB (NF‑κB) ligand (RANKL)‑induced osteoclastogenesis. Osteoclast precursor RAW264...
September 27, 2017: Molecular Medicine Reports
Tianyun Liu, Shirbi Ish-Shalom, Wen Torng, Aleix Lafita, Christian Bock, Matthew Mort, David N Cooper, Spencer Bliven, Guido Capitani, Sean D Mooney, Russ B Altman
Our goal is to answer the question: compared with experimental structures, how useful are predicted models for functional annotation? We assessed the functional utility of predicted models by comparing the performances of a suite of methods for functional characterization on the predictions and the experimental structures. We identified 28 sites in 25 protein targets to perform functional assessment. These 28 sites included nine sites with known ligand binding (holo-sites), nine sites that are expected or suggested by experimental authors for small molecule binding (apo-sites), and ten sites containing important motifs, loops, or key residues with important disease-associated mutations...
October 4, 2017: Proteins
Amy K Erbe, Wei Wang, Lakeesha Carmichael, KyungMann Kim, Eneida A Mendonca, Yiqiang Song, Dustin Hess, Patrick K Reville, Wendy B London, Arlene Naranjo, Jacquelyn A Hank, Mitchell B Diccianni, Ralph A Reisfeld, Stephen D Gillies, Katherine K Matthay, Susan L Cohn, Michael D Hogarty, John M Maris, Julie R Park, Mehmet Fevzi Ozkaynak, Andrew Gilman, Alice L Yu, Paul M Sondel
PURPOSE: In 2010, a Children's Oncology Group (COG) phase III randomized trial for high-risk neuroblastoma patients (ANBL0032) demonstrated improved event-free survival (EFS) and overall survival (OS) following treatment with an immunotherapy regimen of dinutuximab, GM-CSF, IL-2, and isotretinoin compared to treatment with isotretinoin alone. Dinutuximab, a chimeric anti-GD2 monoclonal antibody, acts in part via NK cells. Killer Immunoglobulin-like Receptors (KIRs) on NK cells and their interactions with KIR-ligands can influence NK cell function...
October 2, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Claudiu N Lungu, Mircea V Diudea
A receptor binding pocket may be occupied by a ligand in various plausible conformations, among which only few ones are energetically related to a biological activity in the physiological efficiency domain. This paper reports the mapping of the conformational space of Lipid II in its interaction with Teixobactin and other Lipid II ligands. Statistical analysis of the resulted data enabled the selection of most favorable ligands and receptor conformations; a score was generated for ordering the ligand-receptor complexes, according to the their lowest energy and in correlation with the efficiency of their biological function...
September 26, 2017: Current Computer-aided Drug Design
Anastasia A Anashkina, Yuri Kravatsky, Eugene Kuznetsov, Alexander A Makarov, Alexei A Adzhubei
Motivation: Modelling with multiple servers that use different algorithms for docking results in more reliable predictions of interaction sites. However, the scoring and comparison of all models by an expert is time-consuming and is not feasible for large volumes of data generated by such modelling. Results: QASDOM Server (Quality ASsessment of DOcking Models) is a simple and efficient tool for real-time simultaneous analysis, scoring and ranking of datasets of receptor-ligand complexes built by a range of docking techniques...
September 18, 2017: Bioinformatics
Nils-Ole Friedrich, Christina de Bruyn Kops, Florian Flachsenberg, Kai Sommer, Matthias Rarey, Johannes Kirchmair
We assess and compare the performance of eight commercial conformer ensemble generators (ConfGen, ConfGenX, cxcalc, iCon, MOE LowModeMD, MOE Stochastic, MOE Conformation Import and OMEGA) and one leading free algorithm, the distance geometry (DG) algorithm implemented in RDKit. The comparative study is based on a new version of the Platinum Diverse Dataset, a high-quality benchmarking dataset of 2859 protein-bound ligand conformations extracted from the PDB. Differences in the performance of commercial algorithms are much smaller than those observed for free algorithms in our previous study (J...
October 2, 2017: Journal of Chemical Information and Modeling
David Xu, Khuchtumur Bum-Erdene, Yubing Si, Donghui Zhou, Mona Ghozayel, Samy Meroueh
Tight protein-protein interactions (Kd < 100 nM) that occur over a large binding interface (> 1,000 Å2) are highly challenging to disrupt with small molecules. Historically, the design of small molecules to inhibit protein-protein interactions has focused on mimicking the position of interface protein ligand sidechains. Here, we explore mimicry of the pairwise intermolecular interactions of the native protein ligand with residues of the protein receptor to enrich commercial libraries for small-molecule inhibitors of tight interaction (Kd = 1 nM) between the urokinase receptor (uPAR) and its ligand urokinase (uPA)...
September 27, 2017: ChemMedChem
Liang Cheng, Zheng Zhang, Guangming Li, Feng Li, Li Wang, Liguo Zhang, Sandra M Zurawski, Gerard Zurawski, Yves Levy, Lishan Su
TLR ligands (TLR-Ls) represent a class of novel vaccine adjuvants. However, their immunologic effects in humans remain poorly defined in vivo. Using a humanized mouse model with a functional human immune system, we investigated how different TLR-Ls stimulated human innate immune response in vivo and their applications as vaccine adjuvants for enhancing human cellular immune response. We found that splenocytes from humanized mice showed identical responses to various TLR-Ls as human PBMCs in vitro. To our surprise, various TLR-Ls stimulated human cytokines and chemokines differently in vivo compared to that in vitro...
October 27, 2017: Vaccine
Gouji Toyokawa, Mototsugu Shimokawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Kazuki Takada, Masakazu Katsura, Fumihiro Shoji, Tatsuro Okamoto, Yoshihiko Maehara
OBJECTIVES: Radiologically small-sized adenocarcinomas are special entities of lung cancer, as their radiological and pathological invasiveness determines the surgical procedures applied; however, the clinicopathological features of small-sized lung adenocarcinoma adjoining cystic airspaces (Ca-ADJ) have yet to be fully clarified. The aim of this study was to elucidate the clinicopathological characteristics, including the programmed death ligand 1 (PD-L1) expression, in patients with Ca-ADJ ≤3...
August 29, 2017: European Journal of Cardio-thoracic Surgery
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