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RANK ligand

Paul J Fischer, Shuruthi Senthil, Jeremy T Stephan, McKinley L Swift, Meghan D Storlie, Emily T Chan, Matthew V Vollmer, Victor G Young
A series of zerovalent group VI metal complexes of tris(diisopropylphosphinomethyl)phenylborate ([PhB(CH2PiPr2)3]-, PhBPiPr3), including [PPN][M(CO)3(PhBPiPr3)] (M = Cr, Mo, W) and the first bimetallics in which PhBPiPr3 serves as a bridging ligand via binding M(CO)3 units at the three phosphorus atoms and the borate phenyl substituent, have been synthesized and fully characterized. Two new tris(phosphinomethyl)borates featuring 3,5-dimethylphenyl and 3,5-bis(trifluoromethyl)phenyl borate substituents were prepared as crystallographically characterized thallium salts, and metallated giving their inaugural transition metal complexes [PPN][M(CO)3(((3,5-Me)C6H3)BPPh3)] and [PPN][M(CO)3(((3,5-CF3)C6H3)BPPh3)]...
April 18, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Natheer H Al-Rawi, Ammar K Al-Siraj, Ahlam H Majeed
Objectives: The aim of this study was to compare the expression of receptor-activated nuclear factor kappa B (RANK) with its ligand (RANKL) and matrix metalloproteinase-2 (MMP2) in solid/multicystic ameloblastomas (ABs) and keratocystic odontogenic tumors (KOTs). Materials and Methods: The expression of MMP2, RANK, and RANKL molecules was evaluated in 13 ABs and 14 KOTs by immunohistochemistry. The expressions were calculated in the odontogenic epithelial cells as well as the stromal cells...
January 2018: European Journal of Dentistry
Tae Hoon Kim, Hye Jung Ihn, Kiryeong Kim, Hye-Sung Cho, Hong-In Shin, Yong Chul Bae, Eui Kyun Park
In this study, we have shown that methyl-3,5-di-O-caffeoyl-epi-quinate, a naturally occurring compound isolated from Ainsliaea acerifolia, inhibits receptor activator of nuclear factor-κB ligand (RANKL)-induced formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and the expression of osteoclast marker genes. Methyl-3,5-di-O-caffeoyl-epi-quinate also inhibited RANKL-induced activation of p38, Akt and extracellular signal-regulated kinase (ERK) as well as the expression of nuclear factor of activated T-cell (NFATc1), the key regulator of osteoclast differentiation...
April 9, 2018: Bioorganic & Medicinal Chemistry Letters
Yina Li, Laura A Jacox, Shannyn H Little, Ching-Chang Ko
Orthodontic tooth movement relies on coordinated tissue resorption and formation in the surrounding bone and periodontal ligament. Tooth loading causes local hypoxia and fluid flow, initiating an aseptic inflammatory cascade culminating in osteoclast resorption in areas of compression and osteoblast deposition in areas of tension. Compression and tension are associated with particular signaling factors, establishing local gradients to regulate remodeling of the bone and periodontal ligament for tooth displacement...
April 2018: Kaohsiung Journal of Medical Sciences
Deniz Sezlev Bilecen, Hasan Uludag, Vasif Hasirci
Osteoporosis, which is characterized by low bone mineral density and susceptibility to fracture, is caused by increased osteoclastic activity. Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL)/RANK signaling plays an important role in osteoclast differentiation and activation. The current treatment strategies for osteoporosis do not directly address this underlying cause and generates undesired side effects. This led to emergence of controlled delivery systems to increase drug bioavailability and efficacy specifically at the bone tissue...
March 14, 2018: Tissue Engineering. Part A
Irene Zolfaroli, Juan J Tarín, Antonio Cano
Evidence from different sources sustains a pro-oncogenic role of hormones, estrogens and progestogens, on the breast. The issue is of interest for young women, who are exposed to the hormonal changes imposed by the ovarian cycle and, often, take hormones with contraceptive purposes. Experimental and clinical studies show that both estrogens and progesterone are involved in mammary development during puberty and lactation, the changes being observed across mammalian species, including humans. Estrogen receptors, and more particularly the alpha isoform, participate in molecular processes of stem cells differentiation and epithelial proliferation through paracrine actions implicating growth factors...
March 28, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Qi-Wen Man, Wen-Qun Zhong, Jian-Gang Ren, Jin-Yuan Liu, Yue-Yu Zheng, Rui-Fang Li, B Fidele Nyimi, Gang Chen, Yi-Fang Zhao, Bing Liu
The aim of this study was to examine the level and basic characteristics of cell‑derived microparticles (MPs) in the cyst fluids of odontogenic keratocysts (OKCs). For this purpose, MPs from the cyst fluids (CFMPs) of OKCs were purified by a classic differential centrifugation method and characterized by a transmission electron microscope and fluorescence microscope. Flow cytometric analysis was used to determine the size, concentration and cellular origins of the CFMPs. Moreover, the expression level of receptor activator for nuclear factor‑κB ligand in the OKCs was evaluated by immunohistochemical staining and then analyzed for its correlation with the concentration of CFMPs by Spearman's rank correlation test...
April 5, 2018: International Journal of Oncology
Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Katsuyuki Takahashi, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators...
April 3, 2018: Journal of Translational Medicine
Grégory Menchon, Laurent Maveyraud, Georges Czaplicki
Rational drug design is essential for new drugs to emerge, especially when the structure of a target protein or catalytic enzyme is known experimentally. To that purpose, high-throughput virtual ligand screening campaigns aim at discovering computationally new binding molecules or fragments to inhibit a particular protein interaction or biological activity. The virtual ligand screening process often relies on docking methods which allow predicting the binding of a molecule into a biological target structure with a correct conformation and the best possible affinity...
2018: Methods in Molecular Biology
Álvaro Martínez-Camarena, Estefanía Delgado-Pinar, Concepción Soriano, Javier Alarcón, José M Llinares, Roberto Tejero, Enrique García-España
The binuclear Cu2+ complex of a pyridinophane polyamine ligand ranking amongst the fastest SOD mimetics so far reported displays a remarkable SOD activity enhancement when grafted to the surface of boehmite (γ-AlO(OH)) nanoparticles (BNPs).
March 29, 2018: Chemical Communications: Chem Comm
Sruthi Murlidaran, Grace Brannigan
Efforts to detect binding modes of general anesthetics (GAs) for pentameric ligand-gated ion channels (pLGICs) are often complicated by a large number of indicated sites, as well as the challenges of ranking sites by affinity and determining which sites are occupied at clinical concentrations. Physics-based computational methods offer a powerful route for determining affinities of ligands to isolated binding sites, but preserving accuracy is essential. This chapter describes a step-by-step approach to multiple methods for identifying candidate sites and quantifying binding affinities and also discusses limitations and common pitfalls...
2018: Methods in Enzymology
Chang-Hong Li, Lin-Lin Xu, Lei-Lei Jian, Ruo-Han Yu, Jin-Xia Zhao, Lin Sun, Guo-Hong Du, Xiang-Yuan Liu
Tofacitinib, a small molecule JAK inhibitor, has been widely used to reduce inflammation and inhibit progression of bone destruction in rheumatoid arthritis. STAT3, a downstream signaling molecule of JAK, plays a key role in the activation of signaling in response to inflammatory cytokines. Thus, targeting STAT3 may be an inspiring strategy for treating osteoclast-related diseases such as rheumatoid arthritis. In this study, we first investigated the effects of Stattic, a STAT3 inhibitor, on receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis...
March 24, 2018: International Immunopharmacology
Brigette B Y Ma, Wan-Teck Lim, Boon-Cher Goh, Edwin P Hui, Kwok-Wai Lo, Adam Pettinger, Nathan R Foster, Jonathan W Riess, Mark Agulnik, Alex Y C Chang, Akhil Chopra, Julie A Kish, Christine H Chung, Douglas R Adkins, Kevin J Cullen, Barbara J Gitlitz, Dean W Lim, Ka-Fai To, K C Allen Chan, Y M Dennis Lo, Ann D King, Charles Erlichman, Jun Yin, Brian A Costello, Anthony T C Chan
Purpose This multinational study evaluated the antitumor activity of nivolumab in nasopharyngeal carcinoma (NPC). Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Patients and Methods Patients with multiply pretreated recurrent or metastatic NPC were treated with nivolumab until disease progression. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity. The expression of programmed death-ligand 1 (PD-L1) and human leukocyte antigens A and B in archived tumors and plasma clearance of Epstein-Barr virus DNA were correlated with ORR and survival...
March 27, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Xin Zhang, Jason B Cross, Jan Romero, Alexander Heifetz, Eric Humphries, Katie Hall, Yuchuan Wu, Sabrina Stucka, Jing Zhang, Haoqun Chandonnet, Blaise Lippa, M Dominic Ryan, J Christian Baber
Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. There is limited experimental data on CCR9 and its ligands, complicating efforts to identify new small molecule antagonists. We present here results of a successful virtual screening and rational hit-to-lead campaign that led to the discovery and initial optimization of novel CCR9 antagonists. This work uses a novel data fusion strategy to integrate the output of multiple computational tools, such as 2D similarity search, shape similarity, pharmacophore searching, and molecular docking, as well as the identification and incorporation of privileged chemokine fragments...
March 26, 2018: Journal of Computer-aided Molecular Design
Anoop Kumar, Padma Charan Behera, Naresh Kumar Rangra, Suddhasattya Dey, Kamal Kant
Background: Pyrethroids have prominently known for their insecticidal actions worldwide, but recent reports as anticancer and antiviral applications gained a lot of interest to further understand their safety and immunotoxicity. Objective: This encouraged us to carry out our present study to evaluate the interactions of pyrethroids toward adaptive immune cell receptors. Materials and Methods: Type 1 and Type 2 pyrethroids were tested on T (CD4 and CD8) and B (CD28 and CD45) immune cell receptors using Maestro 9...
January 2018: Pharmacognosy Magazine
Rieko Matsuike, Hideki Tanaka, Kumiko Nakai, Mai Kanda, Maki Nagasaki, Fumiko Murakami, Chika Shibata, Kotoe Mayahara, Akira Nakajima, Natsuko Tanabe, Takayuki Kawato, Masao Maeno, Noriyoshi Shimizu
AIMS: During orthodontic treatment, facilitating osteoclastic bone resorption in the alveolar bone exposed to the compressive force (CF) is an important factor for tooth movement. The present study investigated the effect of CF stimulation on the differentiation of RAW264.7 cells from precursors to mature osteoclasts. MAIN METHODS: The cells were continuously stimulated with 0.3, 0.6, or 1.1 g/cm2 CF-which was generated by increasing the volume of culture medium in the wells of a 96-well plate-in the presence or absence of receptor activator of nuclear factor κB (RANK) ligand (RANKL) for 4 days...
March 20, 2018: Life Sciences
Zhengbo Song, Guoping Cheng, Chunwei Xu, Wenxian Wang, Yang Shao, Yiping Zhang
BACKGROUND: Mutations in polymerase ε (POLE), a DNA polymerase involved in DNA replication and repair, have been investigated in endometrial cancers and response to programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) immunotherapy. However, the frequency of POLE gene mutation in patients with non-small cell lung cancer (NSCLC) has not been reported. MATERIALS AND METHODS: We assessed POLE mutation in 319 patients with NSCLC by next-generation sequencing (NGS) of 416 cancer-associated genes...
April 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
M Liu, Y Sun, Q Zhang
Extracellular vesicles (EVs), as nanometer-scale particles, include exosomes, microvesicles, and apoptotic bodies. EVs are released by most cell types, such as bone marrow stem cells, osteoblasts, osteoclasts, and immune cells. In bone-remodeling microenvironments, EVs deliver specific proteins (e.g., tenascin C and Sema4D), microRNAs (e.g., miR-214-3p, miR-183-5p, and miR-196a), and other growth factors (e.g., bone morphogenetic protein 1 to 7 and transforming growth factor β1) to osteoblasts and regulate bone formation...
March 1, 2018: Journal of Dental Research
Adi L Tarca, Xiaofeng Gong, Roberto Romero, Wenxin Yang, Zhongqu Duan, Hao Yang, Chengfang Zhang, Peixuan Wang
Crowdsourcing has emerged as a framework to address methodological challenges in omics data analysis and assess the extent to which omics data are predictive of phenotypes of interest. The sbv IMPROVER Systems Toxicology Challenge was designed to leverage crowdsourcing to determine whether human blood gene expression levels are informative of current and past smoking. Participating teams were invited to use a training gene expression dataset to derive parsimonious models (up to 40 genes) that can accurately classify subjects into exposure groups: smokers, former smokers that quit for at least one year, and never-smokers...
February 2018: Computational Toxicology
Jaesung Seo, Hyun Jung Kee, Hae-Ji Choi, Jae Eun Lee, Soo-Yeon Park, Seung-Hyun Lee, Mi-Hyeon Jeong, Garam Guk, SooYeon Lee, Kyung-Chul Choi, Yoon Young Choi, Hyunki Kim, Sung Hoon Noh, Ho-Geun Yoon, Jae-Ho Cheong
Wntless/GPR177 functions as WNT ligand carrier protein and activator of WNT/β-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n=184; GSE66229, n=300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n=909)...
March 20, 2018: BMB Reports
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