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https://www.readbyqxmd.com/read/28347132/radiolabeled-peptides-current-and-new-perspectives
#1
Marta Opalinska, Alicja Hubalewska-Dydejczyk, Anna Sowa-Staszczak
Radiolabeled peptides have been the subject of research for over 20 years and during that time possibility/variety of peptide receptor imaging and later targeted radiotherapy increased significantly. The targeted receptors belong to the large family of G-protein-coupled receptors or tyrosine kinases receptors partially connected with them. They both regulate large signaling networks, control multiple cell functions and are implicated in many diseases including cancers. The essential feature of peptides used in nuclear medicine involves their ability to binding with high affinity and specify to their receptors overexpressed on tumor cells...
June 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28346829/polymorphisms-in-the-glucocorticoid-receptor-gene-and-associations-with-glucocorticoid-induced-avascular-osteonecrosis-of-the-femoral-head
#2
Zhanqin Zhao, Yun Xue, Dun Hong, Hongjun Zhang, Zhigang Hu, Shunwu Fan, Haixiao Chen
AIMS: Individual sensitivity to glucocorticoid (GC) therapy might play a pivotal role in the development of GC-induced avascular necrosis of the femoral head (GANFH). In a growing number of studies, common polymorphisms of the glucocorticoid receptor gene (nuclear receptor subfamily 3 group C member 1 [NR3C1]) have been associated with variability in the individual sensitivity to GCs. However, whether the NR3C1 gene polymorphisms actually influence the susceptibility of GANFH remains unknown...
March 27, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28346775/hyperinsulinism-causing-mutations-cause-multiple-molecular-defects-in-sur1-nbd1
#3
Claudia Paola Alvarez, Marijana Stagljar, D Ranjith Muhandiram, Voula Kanelis
The sulfonylurea receptor 1 (SUR1) protein forms the regulatory subunit in ATP sensitive K+ (KATP) channels in the pancreas. SUR proteins are members of the ATP-binding cassette (ABC) superfamily of proteins. Binding and hydrolysis of MgATP at the SUR nucleotide binding domains (NBDs) lead to channel opening. Pancreatic KATP channels play an important role in insulin secretion. SUR1 mutations that result in increased channel opening ultimately inhibit insulin secretion and lead to neonatal diabetes. In contrast, SUR1 mutations that disrupt trafficking and/or decrease gating of KATP channels cause congenital hyperinsulinism, where over secretion of insulin occurs even in the presence of low glucose...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28346354/anti-inflammatory-properties-of-irisin-mediator-of-physical-activity-are-connected-with-tlr4-myd88-signaling-pathway-activation
#4
Agnieszka Irena Mazur-Bialy, Ewa Pocheć, Marcin Zarawski
Irisin, an adipomiokine known as a mediator of physical activity, induces the browning of adipose tissue and it has potentially protective properties in the development of obesity-related states, such as insulin resistance, arteriosclerosis, and type 2 diabetes. Despite numerous studies conducted on this factor, still little is known about its impact on the functioning of immunocompetent cells, but its potential anti-inflammatory properties were previously suggested. In the current study we investigated the role of irisin (0-100 nM) in the downstream pathway activation of Toll-like receptor 4 (TLR4) in RAW 264...
March 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28346099/development-of-novel-cell-lines-for-high-throughput-screening-to-detect-estrogen-related-receptor-alpha-modulators
#5
Christina T Teng, Jui-Hua Hsieh, Jinghua Zhao, Ruili Huang, Menghang Xia, Negin Martin, Xiaohua Gao, Darlene Dixon, Scott S Auerbach, Kristine L Witt, B Alex Merrick
Estrogen-related receptor alpha (ERRα), the first orphan nuclear receptor discovered, is crucial for the control of cellular energy metabolism. ERRα and its coactivator, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), are required for rapid energy production in response to environmental challenges. They have been implicated in the etiology of metabolic disorders such as type 2 diabetes and metabolic syndrome. ERRα also plays a role in the pathogenesis of breast cancer. Identification of compounds that modulate ERRα signaling may elucidate environmental factors associated with these diseases...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345770/effect-of-1-25-oh-2-d3-and-20-oh-d3-on-interleukin-1%C3%AE-stimulated-interleukin-6-and-8-production-by-human-gingival-fibroblasts
#6
V Nakashyan, D A Tipton, A Karydis, R Livada, S H Stein
BACKGROUND AND OBJECTIVE: Vitamin D-1,25(OH)2 D3 or 1,25D3-maintains healthy osseous tissue, stimulates the production of the antimicrobial peptide cathelicidin and has anti-inflammatory effects, but it can cause hypercalcemia. Evidence links diminished serum levels of 1,25D3 with increased gingival inflammation. Periodontitis progression is associated with increased local production of inflammatory mediators by immune cells and gingival fibroblasts. These include interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8, both regulated by signaling pathways, including NF-κB and MAPK/AP-1...
March 27, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28345252/amplification-of-fsh-signaling-by-cftr-and-nuclear-soluble-adenylyl-cyclase-in-the-ovary
#7
Hui Chen, Hsiao Chang Chan
cAMP/PKA pathway is one of the most important signaling pathways widely distributed in most eukaryotic cells. The activation of the canonical cAMP/PKA pathway depends on transmembrane adenylyl cyclase (tmAC). Recently, soluble adenylyl cyclase (sAC), which is activated by HCO3(-) or Ca(2+) , emerges to provide an alternative way to activate cAMP/PKA pathway with the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl(-) / HCO3(-) -conducting anion channel, as a key player. This review summarizes new progress in the investigation of the CFTR/HCO3(-) -dependent sAC signaling and its essential role in various reproductive processes, particularly in ovarian functions...
March 27, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28344923/impact-of-drug-treatment-at-neonatal-ages-on-variability-of-drug-metabolism-and-drug-drug-interactions-in-adult-life
#8
Stephanie Piekos, Chad Pope, Austin Ferrara, Xiao-Bo Zhong
PURPOSE OF REVIEW: As the number of patients taking more than one medication concurrently continues to increase, predicting and preventing drug-drug interactions (DDIs) is now more important than ever. Administration of one drug can cause changes in the expression and activity of drug metabolizing enzymes (DMEs) and alter the efficacy or toxicity of other medications that are substrates for these enzymes, resulting in a DDI. In today's medical practice, potential DDIs are evaluated based on the current medications a patient is taking with little regard to drugs the patient has been exposed to in the past...
February 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28344765/new-insights-on-thyroid-hormone-mediated-regulation-of-herpesvirus-infections
#9
REVIEW
Robert W Figliozzi, Feng Chen, S Victor Hsia
Thyroid hormone (T3) has been suggested to participate in the regulation of herpesvirus replication during reactivation. Clinical observations and in vivo experiments suggest that T3 are involved in the suppression of herpes virus replication. In vitro, differentiated LNCaP cells, a human neuron-like cells, further resisted HSV-1 replication upon addition of T3. Previous studies indicate that T3 controlled the expression of several key viral genes via its nuclear receptors in differentiated LNCaP cells. Additional observation showed that differentiated LNCaP cells have active PI3K signaling and inhibitor LY294002 can reverse T3-mediated repression of viral replication...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28344201/stenotic-bicuspid-and-tricuspid-aortic-valves%C3%A3-micro-computed-tomography-and-biological-indices-of-calcification
#10
Piotr Mazur, Ewa Wypasek, Bogusław Gawęda, Dorota Sobczyk, Przemysław Kapusta, Joanna Natorska, Krzysztof Piotr Malinowski, Jacek Tarasiuk, Maciej Bochenek, Sebastian Wroński, Katarzyna Chmielewska, Bogusław Kapelak, Anetta Undas
BACKGROUND: Valve calcification is well estimated by ex-vivo micro-computed tomography (micro-CT). The objective of this study was to investigate the associations between micro-CT findings and biological indices of calcification in aortic stenosis (AS), as well as differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV).Methods and Results:Aortic valves and plasma were obtained from patients undergoing valve surgery. Valves were dissected and underwent micro-CT, genetic analyses, and calcium content assessment...
March 24, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28344171/lipopolysaccharide-induced-interleukin-6-production-is-mediated-through-activation-of-erk-1-2-p38-mapk-mek-and-nf%C3%AE%C2%BAb-in-chicken-thrombocytes
#11
C Winkler, F Ferdous, M Dimmick, T Scott
Thrombocytes express Toll-like receptor 4 and apparently use both mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB) pathways for nuclear signaling. However, it is not well known if the same enzyme systems found in mammalian cells are fully functional in chickens. Therefore, kinase inhibitors were used with thrombocytes to block kinases in lipopolysaccharide (LPS) stimulated cells to determine if interleukin (IL)-6 expression and production would be diminished...
March 23, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28344054/the-role-of-cardiac-energy-metabolism-in-cardiac-hypertrophy-and-failure
#12
REVIEW
Tomi Tuomainen, Pasi Tavi
In mammalian heart, incessant production of cellular energy is vital for maintaining continuous mechanical pumping function providing the body for oxygen and nutrients. To ensure this essential function, cardiac muscle adapt to increased energy demand or compromised energy supply by reprogramming the network of genes whose products are necessary to match the production of energy to consumption. Failure in this regulation leads to severe cardiac dysfunction and has been associated with cardiac pathogenesis including cardiac hypertrophy, failure and diabetes...
March 24, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28343998/carnosic-acid-ca-attenuates-collagen-induced-arthritis-in-db-db-mice-via-inflammation-suppression-by-regulating-ros-dependent-p38-pathway
#13
Guangtao Xia, Xia Wang, Hongsheng Sun, Yuhong Qin, Min Fu
Rheumatoid arthritis (RA) is a multifactorial autoimmune disease, characterized by inflammation of synovial joints. Carnosic acid (CA) is a phenolic diterpene isolated from Rosmarinus officinails, playing a central role in cytoprotective responses to oxidative stress and inflammation response. Our study aimed to investigate the effects of CA on RA progression in diabetic animals. Carnosic acid (CA) was used to treat collagen-induced arthritis (CIA)-induced db/db mice. Blood glucose, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were investigated to explore insulin resistance...
March 23, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28343601/effects-of-rg7652-a-monoclonal-antibody-against-pcsk9-on-ldl-c-ldl-c-subfractions-and-inflammatory-biomarkers-in-patients-at-high-risk-of-or-with-established-coronary-heart-disease-from-the-phase-2-equator-study
#14
Amos Baruch, Sofia Mosesova, John D Davis, Nageshwar Budha, Alexandr Vilimovskij, Robert Kahn, Kun Peng, Kyra J Cowan, Laura Pascasio Harris, Thomas Gelzleichter, Josh Lehrer, John C Davis, Whittemore G Tingley
RG7652 (MPSK3169A), a fully human immunoglobulin G1 (IgG1) monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9), blocks the interaction between PCSK9 and low-density lipoprotein (LDL) receptor. EQUATOR (ClinicalTrials.govNCT01609140), a randomized, double-blind, and dose-ranging phase 2 study, evaluated RG7652 in patients (1) at high risk for or (2) with coronary heart disease (CHD). The primary end point was change in LDL cholesterol (LDL-C) from baseline to day 169. Patients (n = 248; median age, 64 years; 57% men; 52% with established CHD; 82% on statins) with baseline LDL-C levels of 90 to 250 mg/dl (mean, 126 mg/dl) continuing on standard-of-care therapy were randomized to receive 1 of 5 RG7652 doses or placebo, subcutaneously every 4, 8, or 12 weeks for 24 weeks...
March 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28343338/expression-of-typical-osteoclast-markers-by-pbmcs-after-peg-induced-fusion-as-a-model-for-studying-osteoclast-differentiation
#15
Luz M Castillo, Carlos A Guerrero, Orlando Acosta
Bone is a metabolically active organ subjected to continuous remodeling process that involves resorption by osteoclast and subsequent formation by osteoblasts. Osteoclast involvement in this physiological event is regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). Fusion of mono-nuclear pre-osteoclasts is a critical event for osteoclast differentiation and for bone resorption. Here we show that PBMCs can be successfully fused with polyethylenglicol (PEG) in order to generated viable osteoclast-like cells that exhibit tartrate-resistant acid phosphatase (TRAP) and bone resorptive activities...
March 25, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28343309/breast-cancer-detection-and-tumor-characteristics-in-brca1-and-brca2-mutation-carriers
#16
Julia Krammer, Katja Pinker-Domenig, Mark E Robson, Mithat Gönen, Blanca Bernard-Davila, Elizabeth A Morris, Debra A Mangino, Maxine S Jochelson
PURPOSE: To describe imaging findings, detection rates, and tumor characteristics of breast cancers in a large series of patients with BRCA1 and BRCA2 mutations to potentially streamline screening strategies. METHODS: An IRB-approved, HIPAA-compliant retrospective analysis of 496 BRCA mutation carriers diagnosed with breast carcinoma from 1999 to 2013 was performed. Institutional database and electronic medical records were reviewed for mammography and MRI imaging...
March 25, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28342963/new-insights-into-cellular-cholesterol-acquisition-promoter-analysis-of-human-hmgcr-and-sqle-two-key-control-enzymes-in-cholesterol-synthesis
#17
Vicky Howe, Laura J Sharpe, Anika V Prabhu, Andrew J Brown
BACKGROUND: The two control points of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and squalene monooxygenase (SQLE) are known targets of the transcription factor sterol-regulatory element binding protein-2 (SREBP-2). Yet the location of the sterol-regulatory elements (SREs) and cofactor binding sites, nuclear factor-Y (NF-Y) and specificity protein 1 (Sp1), have not been satisfactorily mapped in the human SQLE promoter, or at all in the human HMGCR promoter...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342850/structural-basis-for-differential-activities-of-enantiomeric-ppar%C3%AE-agonists-binding-of-s35-to-the-alternate-site
#18
Jun Young Jang, Minseob Koh, Hwan Bae, Doo Ri An, Ha Na Im, Hyoun Sook Kim, Ji Young Yoon, Hye-Jin Yoon, Byung Woo Han, Seung Bum Park, Se Won Suh
Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, type 2 diabetes mellitus, and inflammation. Many PPARγ agonists bind to the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i.e., helix H12) of the ligand-binding domain (LBD). More recently, an alternate ligand-binding site was identified in PPARγ LBD; it is located beside the Ω loop between the helices H2' and H3...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342178/return-of-the-lysergamides-part-iii-analytical-characterization-of-n-6-ethyl-6-norlysergic-acid-diethylamide-eth-lad-and-1-propionyl-eth-lad-1p-eth-lad
#19
Simon D Brandt, Pierce V Kavanagh, Folker Westphal, Simon P Elliott, Jason Wallach, Alexander Stratford, David E Nichols, Adam L Halberstadt
The psychoactive properties of lysergic acid diethylamide (LSD) have fascinated scientists across disciplines and the exploration of other analogs and derivatives has been motivated by deepening the understanding of ligand-receptor interactions at the molecular level as well as by the search for new therapeutics. Several LSD congeners have appeared on the new psychoactive substances (NPS) market in the form of blotters or powders. Examples include 1-propionyl-LSD (1P-LSD), AL-LAD and LSZ. The absence of analytical data for novel compounds is a frequent challenge encountered in clinical and toxicological investigations...
March 24, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28341898/functional-block-of-il-17-cytokine-promotes-bone-healing-by-augmenting-foxo1-and-atf4-activity-in-cortical-bone-defect-model
#20
M Dixit, K B Singh, R Prakash, D Singh
We determine the effect of interleukin (IL)-17 neutralizing antibody on new bone regeneration. Anti-IL-17 antibody promoted new bone regeneration in cortical bone defect model by augmenting FOXO1 and ATF4 activity thereby decreasing oxidative stress. Our study demonstrates the bone healing and regeneration potential of neutralizing IL-17antibody in osteoporotic fractures. INTRODUCTION: The immune system plays important role in the fracture healing process. However, fracture healing is prolonged in disorders associated with systemic inflammation...
March 24, 2017: Osteoporosis International
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