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Kappa Receptor

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https://www.readbyqxmd.com/read/28340426/porcine-parvovirus-induces-activation-of-nf-%C3%AE%C2%BAb-signaling-pathways-in-pk-15-cells-mediated-by-toll-like-receptors
#1
Liyan Cao, Jianfei Chen, Yanwu Wei, Hongyan Shi, Xin Zhang, Jing Yuan, Da Shi, Jianbo Liu, Xiangdong Zhu, Xin Wang, Shangjin Cui, Li Feng
Porcine parvovirus (PPV) is a pathogenic factor that primarily induces severe reproductive failure of pregnant swine, which results in extensive losses to the swine industry worldwide. In this study, a potential mechanism of PPV-induced activation of the nuclear transcription factor-kappaB (NF-κB) by infection in porcine kidney cells (PK-15) was elucidated for the first time. The subcellular localization of p65 analyzed by immunofluorescence assay (IFA) showed that PPV infection induced p65 translocation from the cytoplasm to the nucleus...
March 21, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28339199/structure-based-discovery-of-new-antagonist-and-biased-agonist-chemotypes-for-the-kappa-opioid-receptor
#2
Zhong Zheng, Xi-Ping Huang, Thomas J Mangano, Rodger Zou, Xin Chen, Saheem Zaidi, Bryan L Roth, Raymond C Stevens, Vsevolod Katritch
The ongoing epidemics of opioid overdose raises an urgent need for effective anti-addiction therapies and addiction-free painkillers. The κ-opioid receptor (KOR) has emerged as a promising target for both indications, raising demand for new chemotypes of KOR antagonists, as well as G-protein-biased agonists. We employed the crystal structure of the KOR-JDTic complex and ligand-optimized structural templates to perform virtual screening of available compound libraries for new KOR ligands. The prospective virtual screening campaign yielded a high 32% hit rate, identifying novel fragment-like and lead-like chemotypes of KOR ligands...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28333576/epstein-barr-virus-lytic-reactivation-activates-b-cells-polyclonally-and-induces-activation-induced-cytidine-deaminase-expression-a-mechanism-underlying-autoimmunity-and-its-contribution-to-graves-disease
#3
Keiko Nagata, Keisuke Kumata, Yuji Nakayama, Yukio Satoh, Hirotsugu Sugihara, Sayuri Hara, Michiko Matsushita, Satoshi Kuwamoto, Masako Kato, Ichiro Murakami, Kazuhiko Hayashi
Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein-Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity...
March 23, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28333341/systemic-administration-of-sialorphin-attenuates-experimental-colitis-in-mice-via-interaction-with-mu-and-kappa-opioid-receptors
#4
M Salaga, A Mokrowiecka, D Jacenik, A I Cygankiewicz, E Malecka-Panas, R Kordek, W M Krajewska, M K Sobocinska, E Kamysz, J Fichna
Background and Aims: Pharmacological treatment and/or maintenance of remission in inflammatory bowel disease (IBD) is currently one of the biggest challenges in the field of gastroenterology. Here we aimed to assess the anti-inflammatory effect and the mechanism of action of sialorphin, the natural blocker of the endogenous opioid peptide-degrading enzymes neprilysin (NEP) and aminopeptidase N (APN), in the mouse models of IBD and the changes in the expression of these enzymes in IBD patients...
March 18, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28332601/trpm8-in-the-negative-regulation-of-tnf%C3%AE-expression-during-cold-stress
#5
Xin-Pei Wang, Xuan Yu, Xiao-Jin Yan, Fan Lei, Yu-Shuang Chai, Jing-Fei Jiang, Zhi-Yi Yuan, Dong-Ming Xing, Li-Jun Du
Transient Receptor Potential Melastatin-8 (TRPM8) reportedly plays a fundamental role in a variety of processes including cold sensation, thermoregulation, pain transduction and tumorigenesis. However, the role of TRPM8 in inflammation under cold conditions is not well known. Since cooling allows the convergence of primary injury and injury-induced inflammation, we hypothesized that the mechanism of the protective effects of cooling might be related to TRPM8. We therefore investigated the involvement of TRPM8 activation in the regulation of inflammatory cytokines...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326928/cxcr4-signaling-in-macrophages-contributes-to-periodontal-mechanical-hypersensitivity-in-porphyromonas-gingivalis-induced-periodontitis-in-mice
#6
Hidekazu Nagashima, Masamichi Shinoda, Kuniya Honda, Noriaki Kamio, Masahiro Watanabe, Tatsuro Suzuki, Naoyuki Sugano, Shuichi Sato, Koichi Iwata
Background Periodontitis is an inflammatory disease accompanied by alveolar bone loss and progressive inflammation without pain. However, the potential contributors eliminating pain associated with gingival inflammation are unknown. Results we examined the involvement of CXC chemokine receptor type 4 (CXCR4) on the mechanical sensitivity of inflamed periodontal tissue, using a mouse model of periodontitis established by the ligation of the tooth cervix of a maxillary second molar and inoculation with Porphyromonas gingivalis (P...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28326297/coronary-artery-calcium-score-and-bone-metabolism-a-pilot-study-in-postmenopausal-women
#7
Pooneh Salari, Abbasali Keshtkar, Shapour Shirani, Leila Mounesan
BACKGROUND: Since 1991 many studies evaluated the link between cardiovascular diseases and osteoporosis, two age-related conditions, but the main common pathologic pathway has not been determined yet. The histological similarity between arterial calcified plaque and bone matrix and involvement of similar cells and mediators provide a special field of research. Therefore in the present study, we aimed to evaluate the relationship between coronary artery calcium score (CACS) as a surrogate marker of atherosclerosis and bone mediators and parameters in postmenopausal women...
February 2017: Journal of Bone Metabolism
https://www.readbyqxmd.com/read/28323963/an-antibody-to-notch2-reverses-the-osteopenic-phenotype-of-hajdu-cheney-mutant-male-mice
#8
Ernesto Canalis, Archana Sanjay, Jungeun Yu, Stefano Zanotti
Notch receptors play a central role in skeletal development and bone remodeling. Hajdu Cheney Syndrome (HCS), a disease characterized by osteoporosis and fractures, is associated with gain-of-NOTCH2 function mutations. To study HCS, we created a mouse model harboring a point 6955C>T mutation in the Notch2 locus upstream of the proline (P), glutamic acid (E), serine (S) and threonine (T) domain leading to a Q2319X change at the amino acid level. Notch2Q2319X heterozygous mutants exhibited cancellous and cortical bone osteopenia...
January 31, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322829/at-rvd1-modulates-the-activation-of-bronchial-epithelial-cells-induced-by-lipopolysaccharide-and-dermatophagoides-pteronyssinus
#9
Jhony Robison de Oliveira, Paulo Roberto da Silva, Alexandre de Paula Rogério
Bronchial epithelial cells are essential to airways homeostasis; however, they are also involved in exacerbation of airway inflammatory responses of patients with conditions such as asthma. Dermatophagoides pteronyssinus (Dp), the most important allergen, and lipopolysaccharide (LPS), both of which are present in house dust mites (HDM), can activate immune and structural cells (such as bronchial epithelial cells) and modulate the airway inflammation in asthma patients. Resolvin D1 (RvD1) and its epimer aspirin-triggered-resolvin D1 (AT-RvD1) are lipid mediators that are produced during the resolution of inflammation and demonstrate anti-inflammatory and pro-resolution effects in several experimental models including experimental models of allergic airway inflammation...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28322778/down-regulation-of-cyclin-dependent-kinase-4-and-mapk-through-estrogen-receptor-mediated-cell-cycle-arrest-in-human-breast-cancer-induced-by-gold-nanoparticle-tagged-toxin-protein-nkct1
#10
Tanmoy Bhowmik, Antony Gomes
AIM: The aim of this study was to determine whether gold nanoparticles conjugated cytotoxic protein NKCT1 (GNP-NKCT1) acted through the estrogen receptor mediated pathway in MCF-7 cells and to establish the MAPK and PI3k/Akt signal transduction pathway. METHODS: Apoptosis was done by flow cytometry. BrdU incorporation and nuclear proliferating antigen was measured by flow cytometry. Wound healing assay along with matrigel chamber invasion and migration was done...
March 18, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#11
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319095/rcn1-suppresses-er-stress-induced-apoptosis-via-calcium-homeostasis-and-perk-chop-signaling
#12
S Xu, Y Xu, L Chen, Q Fang, S Song, J Chen, J Teng
Endoplasmic reticulum (ER) stress is caused by the disturbance of ER homeostasis and leads to the activation of the unfolded protein response (UPR), which alleviates stress at an early stage and triggers apoptosis if homeostasis fails over a prolonged timeframe. Here, we report that reticulocalbin 1 (RCN1), a member of the CREC family, is transactivated by nuclear factor kappa B (NF-κB) during ER stress and inhibits ER stress-induced apoptosis. The depletion of RCN1 increases the UPR during drug-induced ER stress by activating PRKR-like ER kinase-CCAAT/enhancer-binding protein-homologous protein (PERK-CHOP) signaling, thus inducing apoptosis...
March 20, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28318893/design-and-characterization-of-opioid-ligands-based-on-cycle-in-macrocycle-scaffold
#13
Anna Adamska-Bartłomiejczyk, Rossella De Marco, Luca Gentilucci, Alicja Kluczyk, Anna Janecka
The study reports on a series of novel cyclopeptides based on the structure Tyr-[d-Lys-Phe-Phe-Asp]NH2, a mixed mu and kappa opioid receptor agonist with low nanomolar affinity, in which Phe(4) residue was substituted by cyclic amino acids, such as Pro or its six-membered surrogates, piperidine-2-, 3- or 4-carboxylic acids (Pip, Nip and Inp, respectively). All derivatives exhibited high mu- and moderate delta-opioid receptor affinity, and almost no binding to the kappa-opioid receptor. Conformational analysis suggested that the cis conformation of the peptide bond Phe(3)-Xaa(4) influences receptor selectivity through the control of the position of Phe(3) side chain...
February 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28318829/toll-like-receptor-4-inhibitor-protects-against-retinal-ganglion-cell-damage-induced-by-optic-nerve-crush-in-mice
#14
Yukimichi Nakano, Masamitsu Shimazawa, Kazuki Ojino, Hiroshi Izawa, Hiroto Takeuchi, Yuki Inoue, Kazuhiro Tsuruma, Hideaki Hara
Toll-like receptor 4 (TLR4) plays key roles in innate immune responses and inflammatory reactions. TAK-242 (resatorvid) is a small-molecule cyclohexene derivative that selectively inhibits TLR4 signaling pathways and suppresses inflammatory reactions. Here we investigated the protective effects of TAK-242 against optic nerve crush (ONC) which induces axonal injury like glaucoma in mice. TAK-242 was injected intravitreally immediately after ONC. The effect of TAK-242 was evaluated by measuring the number of fluorogold-labeled retinal ganglion cells (RGCs) at 10 days after ONC...
March 2, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28316065/identification-of-key-genes-and-construction-of-microrna-mrna-regulatory-networks-in-multiple-myeloma-by-integrated-multiple-geo-datasets-using-bioinformatics-analysis
#15
Hongyu Gao, Huihan Wang, Wei Yang
Multiple myeloma (MM) is a common hematological malignancy. To identify key genes and microRNAs in MM, we downloaded two gene expression profiles (GSE16558 and GSE47552) and two microRNA expression profiles (GSE17498 and GSE16558) from the Gene Expression Omnibus (GEO) database. A total of 596 differentially expressed genes (DEGs) and 39 differentially expressed microRNAs (DEMs) were screened out. Pathway analysis showed that upregulated genes were mainly enriched in the "B cell receptor signaling pathway", "Cell cycle" and "NF-kappa B signaling pathway", whereas downregulated genes were mainly enriched in the "Ribosome", "FoxO signaling pathway" and "p53 signaling pathway"...
March 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28315458/cyperus-rotundus-l-extract-suppresses-rankl-induced-osteoclastogenesis-through-nfatc1-c-fos-downregulation-and-prevent-bone-loss-in-ovx-induced-osteoporosis-rat
#16
Chang-Jun Kum, Eun-Young Kim, Jae-Hyun Kim, Bina Lee, Ju-Hee Min, Jun Heo, Jong-Hyun Kim, Mijung Yeom, Youngjoo Sohn, Hyuk-Sang Jung
ETHNOPHARMACOLOGICAL RELEVANCE: Cyperus Rotundus L. (CyR) has been widely used for the treatment of gynecologic disorder. Recent studies have reported that CyR can prevent the formation of cystic follicles and ovarian malfunction. However, the effects of CyR on osteoclastogenesis and postmenopausal osteoporosis remain unknown. AIM OF THE STUDY: This study was aimed to investigate the preventive effects of CyR on RANKL-induced osteoclast formation and ovariectomy (OVX)-induced bone loss...
March 15, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28303499/pregnane-x-receptor-not-nuclear-factor-kappa-b-up-regulates-p-glycoprotein-expression-in-the-brain-of-chronic-epileptic-rats-induced-by-kainic-acid
#17
Nian Yu, Yan-Fang Zhang, Kang Zhang, Yong-Fei Cheng, Hai-Yan Ma, Qing Di
Drug-resistance epilepsy (DRE) is attributed to the brain P-glycoprotein (P-gp) overexpression. We previously reported that nuclear factor-kappa B (NF-κB) played a critical role in regulating P-gp expression at the brain of the acute seizure rats. This study was extended further to investigate the interaction effect of NF-κB and pregnane X receptor (PXR) on P-gp expression at the brain of chronic epileptic rats treated with carbamazepine (CBZ). The chronic epileptic models were induced by the micro-injection of kainic acid (KA) into rats' hippocampus...
March 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28292604/anti-osteoclastogenesis-of-mineral-trioxide-aggregate-through-inhibition-of-the-autophagic-pathway
#18
Xue Cheng, Lingxin Zhu, Jie Zhang, Jingjing Yu, Shan Liu, Fengyuan Lv, Ying Lin, Guojing Liu, Bin Peng
INTRODUCTION: Mineral trioxide aggregate (MTA) regulates bone remodeling, particularly osteoclast differentiation. However, intracellular mechanisms underlying the anti-osteoclastogenesis of MTA remain unclear. This study aimed to evaluate the potential alterations of autophagic pathway during anti-osteoclastogenic effects by MTA in vitro and investigate their underlying mechanisms. METHODS: Osteoclast precursors were treated with MTA extracts containing the receptor activator of nuclear factor-kappa B ligand (RANKL)...
March 11, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28292326/immune-mediators-in-the-tumor-microenvironment-of-prostate-cancer
#19
REVIEW
Jinlu Dai, Yi Lu, Hernan Roca, Jill M Keller, Jian Zhang, Laurie K McCauley, Evan T Keller
Prostate cancer tissue is composed of both cancer cells and host cells. The milieu of host components that compose the tumor is termed the tumor microenvironment (TME). Host cells can be those derived from the tissue in which the tumor originates (e.g., fibroblasts and endothelial cells) or those recruited, through chemotactic or other factors, to the tumor (e.g., circulating immune cells). Some immune cells are key players in the TME and represent a large proportion of non-tumor cells found within the tumor...
March 14, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28292028/bixin-ameliorates-high-fat-diet-induced-cardiac-injury-in-mice-through-inflammation-and-oxidative-stress-suppression
#20
Zhou Xu, Xiang-Qing Kong
Diabetic cardiomyopathy is known as an essential complication of diabetes, a main reason leading to mortality for diabetic patients, and novel therapeutic strategies for treatment are urgently required. Bixin (BX), isolated from the seeds of Bixa orellana, is a carotenoid, possessing anti-inflammatory, anti-tumor and anti-oxidant activities. In our study, we attempted to calculate the role of bixin in cardiac injury progression, and reveal the possible molecular mechanism. Bixin treatment ameliorated cardiac dysfunction through inhibiting fibrosis, inflammation and reactive oxygen species (ROS) generation...
March 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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