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Nuclear Receptors

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https://www.readbyqxmd.com/read/27905561/anti-hu-antibodies-activate-enteric-and-sensory-neurons
#1
Qin Li, Klaus Michel, Anita Annahazi, Ihsan E Demir, Güralp O Ceyhan, Florian Zeller, Lars Komorowski, Winfried Stöcker, Michael J Beyak, David Grundy, Gianrico Farrugia, Roberto De Giorgio, Michael Schemann
IgG of type 1 anti-neuronal nuclear antibody (ANNA-1, anti-Hu) specificity is a serological marker of paraneoplastic neurological autoimmunity (including enteric/autonomic) usually related to small-cell lung carcinoma. We show here that IgG isolated from such sera and also affinity-purified anti-HuD label enteric neurons and cause an immediate spike discharge in enteric and visceral sensory neurons. Both labelling and activation of enteric neurons was prevented by preincubation with the HuD antigen. Activation of enteric neurons was inhibited by the nicotinic receptor antagonists hexamethonium and dihydro-β-erythroidine and reduced by the P2X antagonist pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid (PPADS) but not by the 5-HT3 antagonist tropisetron or the N-type Ca-channel blocker ω-Conotoxin GVIA...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905482/pharmacologic-modulation-of-ror%C3%AE-t-translates-to-efficacy-in-preclinical-and-translational-models-of-psoriasis-and-inflammatory-arthritis
#2
Xiaohua Xue, Pejman Soroosh, Aimee De Leon-Tabaldo, Rosa Luna-Roman, Marciano Sablad, Natasha Rozenkrants, Jingxue Yu, Glenda Castro, Homayon Banie, Wai-Ping Fung-Leung, Luis Santamaria-Babi, Thomas Schlueter, Michael Albers, Kristi Leonard, Alison L Budelsky, Anne M Fourie
The IL-23/IL-17 pathway is implicated in autoimmune diseases, particularly psoriasis, where biologics targeting IL-23 and IL-17 have shown significant clinical efficacy. Retinoid-related orphan nuclear receptor gamma t (RORγt) is required for Th17 differentiation and IL-17 production in adaptive and innate immune cells. We identified JNJ-54271074, a potent and highly-selective RORγt inverse agonist, which dose-dependently inhibited RORγt-driven transcription, decreased co-activator binding and promoted interaction with co-repressor protein...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905067/mathematical-model-of-bone-remodeling-captures-the-antiresorptive-and-anabolic-actions-of-various-therapies
#3
David S Ross, Khamir Mehta, Antonio Cabal
A better understanding of the molecular pathways regulating the bone remodeling process should help in the development of new antiresorptive regulators and anabolic regulators, that is, regulators of bone resorption and of bone formation. Understanding the mechanisms by which parathyroid hormone (PTH) influences bone formation and how it switches from anabolic to catabolic action is important for treating osteoporosis (Poole and Reeve in Curr Opin Pharmacol 5:612-617, 2005). In this paper we describe a mathematical model of bone remodeling that incorporates, extends, and integrates several models of particular aspects of this biochemical system (Cabal et al...
November 30, 2016: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/27904870/preclinical-study-of-68-ga-dotatoc-biodistribution-assessment-in-syrian-rats-and-evaluation-of-absorbed-dose-in-human-organs
#4
Mojdeh Naderi, Samaneh Zolghadri, Hassan Yousefnia, Ali Ramazani, Amir Reza Jalilian
OBJECTIVES: Gallium-68 DOTA-DPhe(1)-Tyr(3)-Octreotide ((68)Ga-DOTATOC) has been applied by several European centers for the treatment of a variety of human malignancies. Nevertheless, definitive dosimetric data are yet unavailable. According to the Society of Nuclear Medicine and Molecular Imaging, researchers are investigating the safety and efficacy of this radiotracer to meet Food and Drug Administration requirements. The aim of this study was to introduce the optimized procedure for (68)Ga-DOTATOC preparation, using a novel germanium-68 ((68)Ge)/(68)Ga generator in Iran and evaluate the absorbed doses in numerous organs with high accuracy...
2016: Asia Oceania Journal of Nuclear Medicine & Biology
https://www.readbyqxmd.com/read/27904108/denosumab-is-effective-for-controlling-serum-calcium-levels-in-patients-with-humoral-hypercalcemia-of-malignancy-syndrome-a-case-report-on-parathyroid-hormone-related-protein-producing-cholangiocarcinoma
#5
Norihiro Ashihara, Koji Nakajima, Yoshiyuki Nakamura, Mutsuhiro Kobayashi, Kumiko Shirahata, Chika Maeda, Takeshi Uehara, Daisuke Gomi, Nobuo Ito
Hypercalcemia resulting in the elevation of serum parathyroid hormone-related protein (PTHrP) and suppression of serum PTH was observed in a patient with advanced cholangiocarcinoma (CCC) and multiple lymph node metastases. We confirmed humoral hypercalcemia of malignancy based on PTHrP-producing CCC. Chemotherapy with gemcitabine and cisplatin could not control the patient's serum PTHrP levels and the patient was affected with bisphosphonate-refractory hypercalcemia. We administered a single dose of denosumab, an anti-receptor activator of nuclear factor-kappaB ligand monoclonal antibody, and the patient's serum calcium levels remained close to the normal range for approximately 3 weeks without additional treatment...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27902699/modeling-cellular-noise-underlying-heterogeneous-cell-responses-in-the-epidermal-growth-factor-signaling-pathway
#6
Kazunari Iwamoto, Yuki Shindo, Koichi Takahashi
Cellular heterogeneity, which plays an essential role in biological phenomena, such as drug resistance and migration, is considered to arise from intrinsic (i.e., reaction kinetics) and extrinsic (i.e., protein variability) noise in the cell. However, the mechanistic effects of these types of noise to determine the heterogeneity of signal responses have not been elucidated. Here, we report that the output of epidermal growth factor (EGF) signaling activity is modulated by cellular noise, particularly by extrinsic noise of particular signaling components in the pathway...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27902592/dynamic-contrast-enhanced-breast-magnetic-resonance-imaging-for-the-prediction-of-early-and-late-recurrences-in-breast-cancer
#7
Eun Jung Choi, HyeMi Choi, Sin Ae Choi, Ji Hyun Youk
The aim of the study was to evaluate dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) features for the prediction of early and late recurrences in patients with breast cancer.Of 1030 breast cancer patients who underwent surgery at our hospital from January 2007 to July 2011, 83 recurrent breast cancer patients were enrolled in this study. We compared MRI features (background parenchymal enhancement [BPE], internal enhancement, adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, kinetic curve types, and quantitative kinetic parameters) and clinico-pathologic variables (age, stage, histologic grade, nuclear grade, existence of lymphovascular invasion and extensive intraductal carcinoma component, and immunohistochemical profiles) between patients with early (≤2...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27902483/androgen-receptor-phosphorylation-status-at-serine-578-predicts-poor-outcome-in-prostate-cancer-patients
#8
Patek Sc, Willder Jm, Heng Js, Taylor B, Horgan Pg, Leung Hy, Underwood Ma, Edwards J
PURPOSE: Prostate cancer growth is dependent upon androgen receptor (AR) activation, regulated via phosphorylation. Protein kinase C (PKC) is one kinase that can mediate AR phosphorylation. This study aimed to establish if AR phosphorylation by PKC is of prognostic significance. METHODS: Immunohistochemistry for AR, AR phosphorylated at Ser-81 (pARS81), AR phosphorylated at Ser-578 (pARS578), PKC and phosphorylated PKC (pPKC) was performed on 90 hormone-naïve prostate cancer specimens...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900520/nuclear-medicine-imaging-of-multiple-myeloma-particularly-in-the-relapsed-setting
#9
REVIEW
Esther G M de Waal, Andor W J M Glaudemans, Carolien P Schröder, Edo Vellenga, Riemer H J A Slart
Multiple myeloma (MM) is characterized by a monoclonal plasma cell population in the bone marrow. Lytic lesions occur in up to 90 % of patients. For many years, whole-body X-ray (WBX) was the method of choice for detecting skeleton abnormalities. However, the value of WBX in relapsing disease is limited because lesions persist post-treatment, which restricts the capacity to distinguish between old, inactive skeletal lesions and new, active ones. Therefore, alternative techniques are necessary to visualize disease activity...
November 29, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27899278/benznidazole-the-trypanocidal-drug-used-for-chagas-disease-induces-hepatic-nrf2-activation-and-attenuates-the-inflammatory-response-in-a-murine-model-of-sepsis
#10
Flavia Lambertucci, Omar Motiño, Silvina Villar, Juan Pablo Rigalli, María de Luján Alvarez, Viviana Catania, Paloma Martín-Sanz, Cristina Ester Carnovale, Ariel Darío Quiroga, Daniel Eleazar Francés, María Teresa Ronco
Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear erythroid 2-related factor 2 (NRF2) in vitro...
November 26, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27898411/radioprotective-effects-of-heat-killed-mycobacterium-tuberculosis-in-cultured-cells-and-radiosensitive-tissues
#11
Yuanyuan Chen, Yang Xu, Jicong Du, Jiaming Guo, Xiao Lei, Jianguo Cui, Cong Liu, Ying Cheng, Bailong Li, Fu Gao, Jintao Ju, Jianming Cai, Yanyong Yang
BACKGROUND: Exposure to ionizing radiation (IR) often causes severe damage to radiosensitive tissues, which limits the use of radiotherapy in cancer patients. Novel safe and effective radioprotectant is urgently required. It has been reported toll like receptor 2 (TLR2) plays a critical role in radioresistance. In this study, we demonstrated the protective effects of Heat-Killed Mycobacterium tuberculosis (HKMT), a potent TLR2 agonist, against IR. METHODS: Cell survival and apoptosis were determined by CCK-8 assay and Annexin V assay, respectively...
November 30, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27897427/structure-based-drug-design-of-mineralocorticoid-receptor-antagonists-to-explore-oxosteroid-receptor-selectivity
#12
Anneli Nordqvist, Gavin O'Mahony, Maria Fridén-Saxin, Marlene Fredenwall, Anders Hogner, Kenneth L Granberg, Anna Aagaard, Stefan Bäckström, Anders Gunnarsson, Tim Kaminski, Yafeng Xue, Anita Dellsén, Eva Hansson, Pia Hansson, Ida Ivarsson, Ulla Karlsson, Krister Bamberg, Majlis Hermansson, Jennie Georgsson, Bo Lindmark, Karl Edman
The mineralocorticoid receptor (MR) is a nuclear hormone receptor involved in regulation of body fluid and electrolyte homeostasis. In this study we explore selectivity triggers for a series of non-steroidal MR antagonists to improve selectivity over other members of the oxosteroid receptor family. A biaryl sulfonamide compound was identified in a high-throughput screening (HTS) campaign. The compound bound to MR with a pKi=6.6, but displayed poor selectivity over the glucocorticoid receptor (GR) and the progesterone receptor (PR)...
November 29, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27897273/a-novel-therapeutic-peptide-as-a-partial-agonist-of-rankl-in-ischemic-stroke
#13
Hitomi Kurinami, Munehisa Shimamura, Hironori Nakagami, Hideo Shimizu, Hiroshi Koriyama, Tomohiro Kawano, Kouji Wakayama, Hideki Mochizuki, Hiromi Rakugi, Ryuichi Morishita
The enhanced receptor activator of nuclear factor-κB (NFκB) ligand (RANKL) and its receptor (RANK) signal have been reported to attenuate ischemic brain injury through inhibition of Toll-like receptor (TLR) 4-mediated inflammation. However, augmentation of the RANKL/RANK signal also accelerates osteoporosis, which is a potential problem in clinical use of RANKL. Therefore, we developed novel peptides, microglial healing peptides (MHPs), which were based on the DE and/or EF loop of RANKL. Among them, MHP1 was the most effective inhibitor of TLR4-induced inflammations in microglia/macrophages...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27897272/analysis-of-the-interaction-of-calcitriol-with-the-disulfide-isomerase-erp57
#14
Elisa Gaucci, Domenico Raimondo, Caterina Grillo, Laura Cervoni, Fabio Altieri, Giulio Nittari, Margherita Eufemi, Silvia Chichiarelli
Calcitriol, the active form of vitamin D3, can regulate the gene expression through the binding to the nuclear receptor VDR, but it can also display nongenomic actions, acting through a membrane-associated receptor, which has been discovered as the disulfide isomerase ERp57. The aim of our research is to identify the binding sites for calcitriol in ERp57 and to analyze their interaction. We first studied the interaction through bioinformatics and fluorimetric analyses. Subsequently, we focused on two protein mutants containing the predicted interaction domains with calcitriol: abb'-ERp57, containing the first three domains, and a'-ERp57, the fourth domain only...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27897222/nadph-oxidase-gp91-phox-contributes-to-rankl-induced-osteoclast-differentiation-by-upregulating-nfatc1
#15
In Soon Kang, Chaekyun Kim
Bone-marrow derived monocyte-macrophages (BMMs) differentiate into osteoclasts by M-CSF along subsequent RANKL stimulation possibly in collaboration with many other unknown cytokines released by pre- or mature osteoblasts. The differentiation process requires receptor activator of nuclear factor kappa-B ligand (RANKL)/RANK signaling and reactive oxygen species (ROS) such as superoxide anion (O2(•-)). Gp91(phox), a plasma membrane subunit of NADPH oxidase (Nox), is constitutively expressed in BMMs and plays a major role in superoxide anion production...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896877/flavonoids-of-herba-epimedii-enhances-bone-repair-in-a-rabbit-model-of-chronic-osteomyelitis-during-post-infection-treatment-and-stimulates-osteoblast-proliferation-in-vitro
#16
Dan Shou, Yang Zhang, Lifeng Shen, Rongzong Zheng, Xiaowen Huang, Zhujun Mao, Zhongming Yu, Nani Wang, Yan Zhu
Flavonoids are the active component of the Herba Epimedii (H. Epimedii), which is commonly used in Asia. This study is to investigate the effect of H. Epimedii on bone repair after anti-infection treatment in vivo. The bioactive-composition group of H. Epimedii (BCGE) contained four flavonoids with the total content of 43.34%. Rabbits with chronic osteomyelitis in response to injection with Staphylococcus aureus were treated with BCGE of 242.70 mg/kg/day intragastrically after vancomycin-calcium sulphate treatment...
November 29, 2016: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/27895513/tumor-suppressor-ing4-inhibits-estrogen-receptor-activity-in-breast-cancer-cells
#17
Madeline M Keenen, Suwon Kim
Resistance to antiestrogen therapy remains a significant problem in breast cancer. Low expression of inhibitor of growth 4 (ING4) in primary tumors has been correlated with increased rates of recurrence in estrogen receptor-positive (ER+) breast cancer patients, suggesting a role for ING4 in ER signaling. This study provides evidence that ING4 inhibits ER activity. ING4 overexpression increased the sensitivity of T47D and MCF7 ER+ breast cancer cells to hormone deprivation. ING4 attenuated maximal estrogen-dependent cell growth without affecting the dose-response of estrogen...
2016: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/27895148/trpc5-regulates-differentiation-through-the-ca2-wnt5a-signal-pathway-in-colorectal-cancer
#18
Zhen Chen, Chunlei Tang, Yaodan Zhu, Mingxu Xie, Dongxu He, Qiongxi Pan, Peng Zhang, Dong Hua, Teng Wang, Linfang Jin, Xiaowei Qi, Yifei Zhu, Xiaoqiang Yao, Jian Jin, Xin Ma
Transient receptor potential channel 5 (TrpC5) is member of the TrpC subgroup, and it forms a receptor-activated non-selective Ca(2+) channel. The architecture of the TrpC5 channel is poorly understood. Here, we report that TrpC5 is a key factor in regulating differentiation in colorectal cancer. Through a study of specimens from a large cohort of patients with colorectal cancer, we found that TrpC5 was highly expressed and its cellular level correlated with tumor grade. We further showed that up-regulated TrpC5 caused a robust [Ca(2+)]i rise, increased Wnt5a expression, and the nuclear translocation of β-catenin, leading to a reduction of cancer differentiation and an increase of cancer cell stemness...
November 28, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27895138/urotensin-ii-inhibitor-eases-neuropathic-pain-by-suppressing-the-jnk-nf-%C3%AE%C2%BAb-pathway
#19
Jing Li, Pan-Pan Zhao, Ting Hao, Dan Wang, Yu Wang, Yang-Zi Zhu, Yu-Qing Wu, Cheng-Hua Zhou
Urotensin II (U-II), a cyclic peptide originally isolated from the caudal neurosecretory system of fishes, can produce proinflammatory effects through its specific G protein-coupled receptor, GPR14. Neuropathic pain, a devastating disease, is related to excessive inflammation in the spinal dorsal horn. However, the relationship between U-II and neuropathic pain has not been reported. This study was designed to investigate the effect of U-II antagonist on neuropathic pain and to understand the associated mechanisms...
February 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/27895089/oxidized-high-density-lipoprotein-induces-macrophage-apoptosis-via-toll-like-receptor-4-dependent-chop-pathway
#20
Shutong Yao, Hua Tian, Li Zhao, Jinguo Li, Libo Yang, Feng Yue, Yanyan Li, Peng Jiao, Nana Yang, Yiwei Wang, Xiangjian Zhang, Shucun Qin
Oxidized high-density lipoprotein (ox-HDL), unlike native HDL that exerts antiatherogenic effects, plays a proatherogenic role. However, the underlying mechanisms are not completely understood. This study was designed to explore the inductive effect of ox-HDL on endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-mediated macrophage apoptosis and its upstream mechanisms. Our results showed that ox-HDL could be ingested by macrophages, causing intracellular lipid accumulation. Like tunicamycin (an ER stress inducer), ox-HDL induced macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α, and upregulation of glucose regulated protein 78 and CHOP, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and CHOP gene silencing...
November 28, 2016: Journal of Lipid Research
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