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ACR-2 receptors

Jia-Nan Zou, Jing Xiao, Sha-Sha Hu, Chen-Sheng Fu, Xiao-Li Zhang, Zhen-Xing Zhang, Yi-Jun Lu, Wei-Jun Chen, Zhi-Bin Ye
BACKGROUND: In vitro experiments have revealed that toll-like receptor 4 (TLR4) pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-γ and TLR4 in IgAN has not been fully studied both in vitro and in vivo...
April 20, 2017: Chinese Medical Journal
Thomas Stock, Dona Fleishaker, Xin Wang, Arnab Mukherjee, Charles Mebus
AIM: To assess efficacy and safety of fosdagrocorat (PF-04171327), a potential dissociated agonist of the glucocorticoid receptor, in rheumatoid arthritis (RA) patients. METHODS: This multicenter, double-blind, parallel-group, active- and placebo-controlled Phase 2 study (NCT00938587) randomized 86 patients (1 : 1 : 1 : 1) to receive fosdagrocorat 10 mg, fosdagrocorat 25 mg, prednisone 5 mg or placebo, all with stable background methotrexate therapy. The primary outcome was change from baseline in Disease Activity Score of 28 joints (DAS28-4[C-reactive protein (CRP)]) after 2 weeks of treatment...
March 22, 2017: International Journal of Rheumatic Diseases
Gerd R Burmester, Iain B McInnes, Joel Kremer, Pedro Miranda, Mariusz Korkosz, Jiri Vencovsky, Andrea Rubbert-Roth, Eduardo Mysler, Matthew A Sleeman, Alex Godwood, Dominic Sinibaldi, Xiang Guo, Wendy I White, Bing Wang, Chi-Yuan Wu, Patricia C Ryan, David Close, Michael E Weinblatt
OBJECTIVES: Despite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA. METHODS: In a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)-C reactive protein (CRP)/erythrocyte sedimentation rate ≥3...
February 17, 2017: Annals of the Rheumatic Diseases
Fudan Zheng, Xiangwei Du, Tsung-Han Chou, Alan P Robertson, Edward W Yu, Brett VanVeller, Richard J Martin
Nematode parasites infect ∼2 billion people world-wide. Infections are treated and prevented by anthelmintic drugs, some of which act on nicotinic acetylcholine receptors (nAChRs). There is an unmet need for novel therapeutic agents because of concerns about the development of resistance. We have selected Asu-ACR-16 from a significant nematode parasite genus, Ascaris suum, as a pharmaceutical target and nicotine as our basic moiety (EC50 6.21 ± 0.56 μM, Imax 82.39 ± 2.52%) to facilitate the development of more effective anthelmintics...
April 2017: International Journal for Parasitology, Drugs and Drug Resistance
Nicolas Dumoitier, Benjamin Chaigne, Alexis Régent, Sébastien Lofek, Maïssa Mhibik, Peter Dorfmüller, Benjamin Terrier, Jonathan London, Alice Bérezné, Nicolas Tamas, Nadine Varin-Blank, Luc Mouthon
OBJECTIVE: To study the role of B lymphocytes in systemic sclerosis (SSc). PATIENTS AND METHODS: Peripheral B cell subpopulations, interleukin 6 (IL-6) and transforming growth factor-beta (TGF-β) productions were analyzed using flow cytometry and multiplex assay. Fibroblasts proliferation rate upon incubation with supernatants of B cells isolated from SSc patients or healthy controls (HC) was assessed using XTT, BrdU and Ki67. Collagen production was assessed using a collagen assay...
December 19, 2016: Arthritis & Rheumatology
Sen Hee Tay, Anna-Marie Fairhurst, Anselm Mak
BACKGROUND/PURPOSE: Neuropsychiatric (NP) events are found in patients with rheumatic diseases, commonly in systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). The standard nomenclature and case definitions for 19 NPSLE syndromes by the American College of Rheumatology (ACR) Committee on Research cover a wide range of NP events seen in both SLE and SS. Despite advances in the understanding of SLE and SS, NP syndromes continue to pose diagnostic challenges. Correct attribution of NP events is critical in determining the correct treatment and prognosis...
February 2017: Autoimmunity Reviews
Nancy L Reinsmoen, James Mirocha, Christopher R Ensor, Marilyn Marrari, George Chaux, Deborah J Levine, Xiaohai Zhang, Adriana Zeevi
BACKGROUND: The presence of antibodies to angiotensin type 1 receptor (AT1R) and endothelin type A receptor (ETAR) is associated with allograft rejection in kidney and heart transplantation. The aim of our study was to determine the impact of AT1R and ETAR antibodies on graft outcome in lung transplantation. METHODS: Pre and posttransplant sera from 162 lung recipients transplanted at 3 centers between 2011 and 2013 were tested for antibodies to AT1R and ETAR by the ELISA assay...
August 4, 2016: Transplantation
John Chan, Chao-Sheng Lo, Yixuan Shi, Isabelle Chenier, Shao-Ling Zhang
OBJECTIVE: We aimed to investigate whether overexpression of heterogeneous nuclear ribonucleoprotein F (HnRNP F, a transcription factor) in renal proximal tubular cells (RPTCs) prevents systemic hypertension and kidney injury in type 2 diabetic db/db transgenic (Tg) mice and study its underlying mechanism (s) of action. DESIGN AND METHOD: Db/db hnRNP F-Tg mice (BKS strain) were generated by cross-breeding of db/m + mice with Tg mice specifically overexpressing HnRNP F in their RPTCs using kidney-specific androgen-regulated protein promoter (KAP2)...
September 2016: Journal of Hypertension
Xiaoguang Xu, Haiyan Huang, Qiang Wang, Ming Cai, Yeyong Qian, Yong Han, Xinying Wang, Yu Gao, Ming Yuan, Liang Xu, Chen Yao, Li Xiao, Bingyi Shi
PURPOSE: IFN-γ is a protypical proinflammatory cytokine that plays a central role in inflammation and acute graft rejection. Accumulating evidence indicates that IFN-γ can exert previously unexpected immunoregulatory activities. However, little is known about the role of IFN-γ secreted by Th1-like regulatory T cells in human kidney transplantation. METHODS: To determine the function of IFN-γ in acute T cell-mediated renal allograft rejection (ACR), we examined serum cytokine expression profiles in ACR patients by human cytokine multiplex immunoassay and analyzed the cellular origins of IFN-γ in peripheral blood and renal allograft biopsies from ACR cases and controls by flow cytometry and immunohistochemistry, respectively...
February 2017: Immunobiology
John Chan, Chao-Sheng Lo, Yixuan Shi, Isabelle Chenier, Shao-Ling Zhang
OBJECTIVE: We aimed to investigate whether overexpression of heterogeneous nuclear ribonucleoprotein F (HnRNP F, a transcription factor) in renal proximal tubular cells (RPTCs) prevents systemic hypertension and kidney injury in type 2 diabetic db/db transgenic (Tg) mice and study its underlying mechanism (s) of action. DESIGN AND METHOD: Db/db hnRNP F-Tg mice (BKS strain) were generated by cross-breeding of db/m + mice with Tg mice specifically overexpressing HnRNP F in their RPTCs using kidney-specific androgen-regulated protein promoter (KAP2)...
September 2016: Journal of Hypertension
Ya Z Liu, Keqi Wang, Xiang Li, Bin Chen
BACKGROUND: The aim of this study was to provide reasonable guidelines for type II diabetes patients with proteinuria to recover their metabolic parameters. METHODS: A cross-sectional study was conducted in selected groups of type 2 diabetic patients. Hypoglycemic and antihypertensive drug use was recorded. Certain physical examinations were conducted including routine urine test, urinary albumin/creatinine ratio (ACR), metabolic parameters of blood glucose and lipid, and other biochemical indicators...
December 2016: Minerva Endocrinologica
Lennart Tonneijck, Mark M Smits, Marcel H A Muskiet, Trynke Hoekstra, Mark H H Kramer, A H Jan Danser, Piet M Ter Wee, Michaela Diamant, Jaap A Joles, Daniël H van Raalte
OBJECTIVE: To investigate effects of dipeptidyl peptidase-4 inhibitor (DPP-4I) sitagliptin or glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide treatment on renal hemodynamics, tubular functions, and markers of renal damage in overweight patients with type 2 diabetes without chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: In this 12-week, randomized, double-blind trial, 55 insulin-naïve patients with type 2 diabetes (mean ± SEM: age 63 ± 7 years, BMI 31...
November 2016: Diabetes Care
Y Umezawa, H Nakagawa, H Niiro, K Ootaki
BACKGROUND: Brodalumab (KHK4827) is a human anti-interleukin-17-receptor A monoclonal antibody. In Japanese patients with moderate-to-severe plaque psoriasis, brodalumab showed rapid and robust efficacy and a favourable safety profile in a 12-week, phase 2, double-blind, randomized controlled trial. OBJECTIVES: To evaluate the long-term safety and efficacy of brodalumab, an extension of a phase 2 trial of Japanese patients with moderate-to-severe psoriasis was performed...
November 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Eric Cuevas, José M Arreola-Guerra, Erick A Hernández-Méndez, Isaac Salcedo, Natalia Castelán, Norma O Uribe-Uribe, Mario Vilatobá, Alan G Contreras-Saldívar, Aczel I Sánchez-Cedillo, Julia B Ramírez, David de Rungs, Julio Granados, Luis E Morales-Buenrostro, Josefina Alberú
BACKGROUND: Angiotensin II type 1 receptor antibodies (AT1Rabs) have been associated with significantly reduced graft survival. Earlier graft loss has been observed in patients who had pretransplant AT1Rabs and posttransplant donor-specific antibodies (DSA). METHODS: The main goal of this retrospective cohort study was to examine the association between AT1Rabs and the time period to detection of de novo human leukocyte antigen (HLA-DSA) posttransplantation in living donor kidney transplant recipients (KTR)...
October 2016: Nephrology, Dialysis, Transplantation
Y Xiong, S Dong, X Zhao, K J Guo, Laura Gasco, Ivo Zoccarato
To study the effects of polyphenolic extract from involucres of Castanea mollissima Blume ( PICB: ), a novel approach using gene expression by real time polymerase chain reaction ( REAL-TIME PCR: ) coupled with metabolomic profiling technique was established to explain the mechanism of PICB on heat-stressed broiler chicks. Four thousand 28-day-old male Arbor Acres (AA) broilers were randomly assigned to 5 groups (4 replicates / group, 20 chicks / replicate), in which group 1 was normal control group fed with basic ration; groups 2, 3, 4, and 5 were fed with the basic ration with a supplementation of 0...
August 1, 2016: Poultry Science
Jan Menne, Dirk Eulberg, Diana Beyer, Matthias Baumann, Frantisek Saudek, Zsuzsanna Valkusz, Andrzej Więcek, Hermann Haller
BACKGROUND: Emapticap pegol (NOX-E36) is a Spiegelmer(®) that specifically binds and inhibits the pro-inflammatory chemokine C-C motif-ligand 2 (CCL2) (also called monocyte-chemotactic protein 1). The objective of this exploratory study was to evaluate the safety and tolerability as well as the renoprotective and anti-diabetic potential of emapticap in type 2 diabetic patients with albuminuria. METHODS: A randomized, double-blind, placebo-controlled Phase IIa study was initiated in 75 albuminuric type 2 diabetics...
April 27, 2016: Nephrology, Dialysis, Transplantation
Seika Takayanagi-Kiya, Yishi Jin
The highly conserved cochaperone DnaJ/Hsp40 family proteins are known to interact with molecular chaperone Hsp70, and can regulate many cellular processes including protein folding, translocation, and degradation. In studies of Caenorhabditis elegans locomotion mutants, we identified a gain-of-function (gf) mutation in dnj-17 closely linked to the widely used e156 null allele of C. elegans GAD (glutamic acid decarboxylase) unc-25 dnj-17 encodes a DnaJ protein orthologous to human DNAJA5. In C. elegans DNJ-17 is a cytosolic protein and is broadly expressed in many tissues...
2016: G3: Genes—Genomes—Genetics
Fudan Zheng, Alan P Robertson, Melanie Abongwa, Edward W Yu, Richard J Martin
Soil-transmitted helminth infections in humans and livestock cause significant debility, reduced productivity and economic losses globally. There are a limited number of effective anthelmintic drugs available for treating helminths infections, and their frequent use has led to the development of resistance in many parasite species. There is an urgent need for novel therapeutic drugs for treating these parasites. We have chosen the ACR-16 nicotinic acetylcholine receptor of Ascaris suum (Asu-ACR-16), as a drug target and have developed three-dimensional models of this transmembrane protein receptor to facilitate the search for new bioactive compounds...
April 2016: International Journal for Parasitology, Drugs and Drug Resistance
Charalampos I Liakos, Gregory P Vyssoulis, Maria I Markou, Nikolaos V Kafkas, Konstantinos P Toutouzas, Dimitrios Tousoulis
The purpose of this study was to assess the role of urine α1 -microglobulin as a marker of hypertension-induced renal damage compared with estimated glomerular filtration rate, (eGFR), urine albumin, and urine albumin-to-creatinine ratio (ACR). Its response on different blood pressure (BP)-lowering drugs was also studied. Sixty never-treated hypertensive patients (65.0% men, 46.9 years, BP 141.4/94.0 mm Hg) were randomized to an irbesartan (an angiotensin receptor blocker [ARB]) or a diltiazem (a nondihydropyridine calcium channel blocker [CCB])-based regimen...
March 18, 2016: Journal of Clinical Hypertension
Ian C Scott, Fowzia Ibrahim, Gemma Simpson, Anna Kowalczyk, Beverley White-Alao, Andrew Hassell, Michael Plant, Selwyn Richards, David Walker, David L Scott
OBJECTIVES: The effectiveness of anakinra (interleukin-1 receptor antagonist) in early rheumatoid arthritis (RA) is unknown. We evaluated the efficacy of anakinra (combined with methotrexate) in a randomised clinical trial of early active RA patients. METHODS: The Combination Anti-Rheumatic Drugs in Early RA-2 (CARDERA-2) trial was a randomised trial of early (duration <1 year) active RA. Patients were randomised to 12 months of: (1) methotrexate or (2) anakinra-methotrexate...
January 2016: Clinical and Experimental Rheumatology
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