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RANK ligand

Keiko Aota, Tomoko Yamanoi, Koichi Kani, Koh-Ichi Nakashiro, Naozumi Ishimaru, Masayuki Azuma
BACKGROUND: Mechanisms underlying immune cells' recruitment and activation into the inflammatory lesions of lip salivary glands (LSGs) from primary Sjögren's syndrome (pSS) patients are incompletely understood. Chemokines play pivotal roles in these processes, so we investigated the clinical significance of chemokine receptor CXCR3 and its ligands in the autoimmune lesions of pSS. METHODS: We histologically determined the grade of LSG samples from 22 pSS patients and subjected the samples to immunofluorescence analysis to determine the expressions of CXCR3 and its ligands: CXCL9, CXCL10, and CXCL11...
June 21, 2018: Journal of Oral Pathology & Medicine
Anton Glasnović, Maristela Stojić, Lidija Dežmalj, Ivana Tudorić-Đeno, Dominik Romić, Vjekoslav Jeleč, Anđelko Vrca, Vladimira Vuletić, Danka Grčević
OBJECTIVES: Our study focused on the RANKL (receptor activator of nuclear factor-κB ligand)/RANK/OPG (osteoprotegerin) axis and selected proinflammatory/immunoregulatory upstream mediators in the peripheral blood (PBL) and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. METHODS: PBL and CSF were collected from healthy controls (n = 35) and MS patients at the clinical onset of the disease (n = 33). In addition, PBL samples were obtained from relapse-remitting (RR)-MS patients (n = 30)...
June 19, 2018: Neuroimmunomodulation
Ju-Hee Kang, Hyungsik Lim, Dong-Seok Lee, Mijung Yim
Osteoclasts (OCs) are resorptive cells responsible for bone erosion in diseases, including osteoporosis, periodontitis and rheumatoid arthritis. Montelukast is a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist clinically used for the treatment of asthma. In the present study, the role of CysLTR1 on OC formation and bone loss was investigated using montelukast. Montelukast inhibited receptor activator of nuclear factor‑κB ligand (RANKL)‑induced OC formation in cultures of mouse bone marrow macrophages...
June 15, 2018: Molecular Medicine Reports
Biao Wang, Dingjun Hao, Zhen Zhang, Wenjie Gao, Hu Pan, Yuan Xiao, Baorong He, Lingbo Kong
Myricitrin is a natural occurring flavonoid glycoside that possesses effects on inhibiting nitric oxide (NO) transmission and preventing inflammatory reaction. Although previous study showed the myricitrin possesses antibone loss effects via reducing the expression of IL-6 and partially suppressing reactive oxygen species (ROS) production. However, the effects of myricitrin on nuclear factor-kappaB ligand (RANKL)-stimulated osteoclastogenesis have not yet been further investigated. The current study was aimed to demonstrating the inhibitory effects of myricitrin on RANKL-stimulated osteoclastogenesis and relevant mechanisms...
June 17, 2018: Journal of Cellular and Molecular Medicine
Hend M Dawood, Reham S Ibrahim, Eman Shawky, Hala M A Hammoda, Aly M Metwally
ETHNOPHARMACOLOGICAL RELEVANCE: Aromatase enzyme (CYP19) is widely known as a critical target protein for treating hormone-dependent breast cancer. Natural products from traditional medicinal plants continue to be an active source of aromatase inhibitors. Meanwhile, high cost of experimental work and low hit rate associated with HTS have stimulated the implementation of in-silico virtual screening to resolve these pitfalls, where coupling of both classical wet lab procedure and VS may offer a more deepened access to bioactive compounds with less work and time waste...
June 14, 2018: Journal of Ethnopharmacology
Chuan Liu, Zhen Cao, Wen Zhang, Jennifer Tickner, Heng Qiu, Chao Wang, Kai Chen, Ziyi Wang, Renxiang Tan, Shiwu Dong, Jiake Xu
The dynamic balance between bone resorption and bone formation is crucial to maintain bone mass. Osteoclasts are key cells that perform bone resorption while osteoblasts and osteocytes function in bone formation. Osteoporosis, a bone metabolism disease characterized by bone loss and degradation of bone microstructure, occurs when osteoclastic bone resorption outstrips osteoblastic bone synthesis. The interaction between receptor activator of nuclear factor κB ligand (RANKL) and RANK on the surface of bone marrow macrophages promotes osteoclast differentiation and activation...
June 15, 2018: Journal of Cellular Physiology
Jaqueline Suemi Hassumi, Gabriel Mulinari-Santos, André Luis da Silva Fabris, Ricardo Garcia Mureb Jacob, Alaíde Gonçalves, Ana Cláudia Rossi, Alexandre Rodrigues Freire, Leonardo Pérez Faverani, Roberta Okamoto
INTRODUCTION: Alveolar bone healing after upper incisor extraction in rats is a classical model of preclinical studies. The underlying morphometric, cellular and molecular mechanism, however, remains imprecise in a unique study. OBJECTIVES: The aim of this study was therefore to characterize the alveolar bone healing after upper incisor extraction in rats by micro computed tomographic (Micro-CT), immunohistochemical and real-time polymerase chain reaction (RT-PCR) analysis...
June 11, 2018: Journal of Applied Oral Science: Revista FOB
Lucas N Alberca, María L Sbaraglini, Juan F Morales, Roque Dietrich, María D Ruiz, Agustina M Pino Martínez, Cristian G Miranda, Laura Fraccaroli, Catalina D Alba Soto, Carolina Carrillo, Pablo H Palestro, Alan Talevi
Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi , an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease Tc PAT12. 1,000 individual linear classifiers were inferred from a balanced dataset...
2018: Frontiers in Cellular and Infection Microbiology
Georgia Melagraki, Georgios Leonis, Evangelos Ntougkos, Vagelis Rinotas, Christos Papaneophytou, Thomas Mavromoustakos, George Kontopidis, Eleni Douni, George Kollias, Antreas Afantitis
The overexpression of Tumor Necrosis Factor (TNF) is directly related to the development of several autoimmune diseases, such as rheumatoid and psoriatic arthritis, inflammatory bowel disease, Crohn's disease, refractory asthma, and multiple sclerosis. Receptor activator of nuclear factor kappa-B ligand (RANKL) belongs to the TNF family, and is the primary mediator of osteoclast-induced bone resorption through interaction with its receptor RANK. The function of RANKL is physiologically inhibited by the action of osteoprotegerin (OPG), which is a decoy receptor that binds to RANKL and prevents the process of osteoclastogenesis...
June 6, 2018: Current Topics in Medicinal Chemistry
Elizabeth Ahern, Heidi Harjunpää, Jake S O'Donnell, Stacey Allen, William C Dougall, Michele W L Teng, Mark J Smyth
Receptor activator of NF-κB ligand (RANKL) and its receptor RANK, are members of the tumor necrosis factor and receptor superfamilies, respectively. Antibodies targeting RANKL have recently been evaluated in combination with anti-CTLA4 in case reports of human melanoma and mouse models of cancer. However, the efficacy of anti-RANKL in combination with antibodies targeting other immune checkpoint receptors such as PD1 has not been reported. In this study, we demonstrated that blockade of RANKL improves anti-metastatic activity of antibodies targeting PD1/PD-L1 and improves subcutaneous growth suppression in mouse models of melanoma, prostate and colon cancer...
2018: Oncoimmunology
Olivier Lamy, Elena Gonzalez Rodriguez, Delphine Stoll, Bérengère Aubry-Rozier, Françoise Livio
Multiple Vertebral Fractures after Denosumab Discontinuation: How to Avoid Them? Abstract. Denosumab is a monoclonal antibody raised against the RANK ligand that inhibits the maturation and activity of osteoclasts. It decreases bone resorption, increases bone density and reduces fracture risk. However, after its discontinuation, a significant rebound effect appears that lasts about two years. It results in increased markers of bone remodeling, a loss of bone density that may be greater than gain, and an increased risk of multiple vertebral fractures...
June 2018: Praxis
F A Shah, P Thomsen, A Palmquist
In lamellar bone, a network of highly oriented interconnected osteocytes is organized in concentric layers. Through their cellular processes contained within canaliculi, osteocytes are highly mechanosensitive and locally modulate bone remodeling. We review the recent developments demonstrating the significance of the osteocyte lacuno-canalicular network in bone maintenance around implant biomaterials. Drilling during implant site preparation triggers osteocyte apoptosis, the magnitude of which correlates with drilling speed and heat generation, resulting in extensive remodeling and delayed healing...
June 1, 2018: Journal of Dental Research
Kimiko Ohgi, Hiroshi Kajiya, Kazuko Goto-T, Fujio Okamoto, Yasunori Yoshinaga, Koji Okabe, Ryuji Sakagami
BACKGROUND: Lectin-like oxidized low-density-lipoprotein receptor 1 (Lox-1) is the receptor for oxidized low-density lipoprotein (oxLDL), a mediator in dyslipidemia. Toll-like receptor (TLR)-2 and - 4 are receptors of lipopolysaccharide (LPS) from Porphyromonas gingivalis, a major pathogen of chronic periodontitis. Although some reports have demonstrated that periodontitis has an adverse effect on dyslipidemia, little is clear that the mechanism is explained the effects of dyslipidemia on osteoclastogenesis...
June 2, 2018: Lipids in Health and Disease
Conor F Hynes, Dong H Kwon, Chaitanya Vadlamudi, Alexander Lofthus, Aya Iwamoto, Joeffrey J Chahine, Sameer Desale, Marc Margolis, Bhaskar V Kallakury, Thomas J Watson, Nadim G Haddad, M Blair Marshall
BACKGROUND: To evaluate the effect of tumor infiltrating lymphocyte (TIL) density and programmed death ligand 1 (PD-L1) expression on the prognosis of esophageal cancer. METHODS: Banked tissue specimens from 53 patients who underwent esophagectomies for malignancy at a single institution over a 6-year period were stained for cluster of differentiation 3 (CD3), cluster of differentiation 8 (CD8) and PD-L1. Tumors were characterized as staining high or low density for CD3 and CD8, as well as positive or negative for PD-L1...
May 30, 2018: Annals of Thoracic Surgery
Jennifer K Bando, Susan Gilfillan, Christina Song, Keely G McDonald, Stanley C-C Huang, Rodney D Newberry, Yasuhiro Kobayashi, David S J Allan, James R Carlyle, Marina Cella, Marco Colonna
While signals that activate group 3 innate lymphoid cells (ILC3s) have been described, the factors that negatively regulate these cells are less well understood. Here we found that the tumor necrosis factor (TNF) superfamily member receptor activator of nuclear factor κB ligand (RANKL) suppressed ILC3 activity in the intestine. Deletion of RANKL in ILC3s and T cells increased C-C motif chemokine receptor 6 (CCR6)+ ILC3 abundance and enhanced production of interleukin-17A (IL-17A) and IL-22 in response to IL-23 and during infection with the enteric murine pathogen Citrobacter rodentium...
May 24, 2018: Immunity
Hiroaki Fuji, Saori Ohmae, Naruto Noma, Masatoshi Takeiri, Hideto Yasutomi, Kazuya Izumi, Moe Ito, Masayasu Toyomoto, Soichiro Iwaki, Kenji Takemoto, Satoru Seo, Kojiro Taura, Shigeaki Hida, Mineyoshi Aoyama, Yasushi Ishihama, Masatoshi Hagiwara, Norihiko Takeda, Etsuro Hatano, Keiko Iwaisako, Shinji Uemoto, Masataka Asagiri
Osteoclasts play a crucial role in osteolytic bone diseases, such as osteoporosis, rheumatoid arthritis, periodontitis, Paget's disease of bone and bone metastatic tumors. Therefore, controlling osteoclast differentiation and function has been considered a promising therapeutic strategy. Here, we show that necrostatin (Nec)-7, an inhibitor of programmed necrosis, strongly suppressed receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption, without compromising macrophage colony-stimulating factor (M-CSF)-supported survival and growth of osteoclast precursor cells...
May 22, 2018: Biochemical and Biophysical Research Communications
Mariama Jaiteh, Alexey Zeifman, Marcus Saarinen, Per Svenningsson, José M Brea, Maria Isabel Loza, Jens Carlsson
Modulation of multiple biological targets with a single drug can lead to synergistic therapeutic effects and has been demonstrated to be essential for efficient treatment of CNS disorders. However, rational design of compounds that interact with several targets is very challenging. Here, we demonstrate that structure-based virtual screening can guide the discovery of multi-target ligands of unrelated proteins relevant for Parkinson's disease. A library with 5.4 million molecules was docked to crystal structures of the A2A adenosine receptor (A2AAR) and monoamine oxidase B (MAO-B)...
May 24, 2018: Journal of Medicinal Chemistry
Fred Saad, Cora N Sternberg, Peter F A Mulders, Daniela Niepel, Bertrand F Tombal
Most men with advanced prostate cancer will develop bone metastases, which have a substantial impact on quality of life. Bone metastases can lead to skeletal-related events (SREs), which place a burden on patients and healthcare systems. For men with castration-resistant prostate cancer (CRPC) and bone metastases, the treatment landscape has evolved rapidly over the past few years. The relatively recent approvals of the hormonal agents abiraterone acetate and enzalutamide, second-line chemotherapy cabazitaxel, and the radiopharmaceutical radium-223 dichloride (radium-223), have provided clinicians with a greater choice of treatments...
May 3, 2018: Cancer Treatment Reviews
Daria B Kokh, Marta Amaral, Joerg Bomke, Ulrich Grädler, Djordje Musil, Hans-Peter Buchstaller, Matthias K Dreyer, Matthias Frech, Maryse Lowinski, François Vallée, Marc Bianciotto, Alexey Rak, Rebecca C Wade
Drug-target residence time (τ), one of the main determinants of drug efficacy, remains highly challeng-ing to predict computationally and, therefore, is usually not considered in the early stages of drug de-sign. Here, we present an efficient computational method, τ-random acceleration molecular dynamics (τRAMD), for the ranking of drug candidates by their residence time and obtaining insights into ligand-target dissociation mechanisms. We assessed τRAMD on a dataset of 70 diverse drug-like ligands of the N-terminal domain of HSP90α, a pharmaceutically important target with a highly flexible binding site, obtaining computed relative residence times with an accuracy of about 2...
May 16, 2018: Journal of Chemical Theory and Computation
Xingtao Ge, Zhijian Chen, Zhenjie Xu, Fang Lv, Kewei Zhang, Yu Yang
Bone loss is one of the important extra-intestinal manifestations in patients with inflammatory bowel diseases (IBDs). Compounds derived from natural products have been used to treat IBDs. However, the role of natural products on IBD-induced bone loss is not completely clarified. In the present study, we observed the effects of dihydroartemisinin (DHA), an antimalaria drug, on IBD and IBD-induced bone loss in a rat model. Chronic IBD model was established in Sprague-Dawley rats by giving them 2.5% dextran sodium sulfate in drinking water...
May 2018: Experimental Biology and Medicine
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