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Macrophage methotrexate

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https://www.readbyqxmd.com/read/28754008/combination-therapy-of-peg-hm-3-and-methotrexate-retards-adjuvant-induced-arthritis
#1
Jingchao Hao, Xiaodong Wu, Sarra Setrerrahmane, Kun Qian, Yueying Hou, Liting Yu, Chenyu Lin, Qianqian Wu, Hanmei Xu
At present, the early phenomenon of inflammatory angiogenesis is rarely studied in Rheumatoid arthritis (RA). Previous research found that PEG-HM-3, an integrin inhibitor, possessed anti-angiogenesis and anti-rheumatic activity. In this study, the advantages of inhibiting angiogenesis and immune cell adhesion and migration, as well as the benefits of anti-arthritis effects, were evaluated using a combination of PEG-HM-3 and methotrexate (MTX). In vitro, spleen cell proliferation and the levels of tumor necrosis factor α (TNF-α) in macrophage supernatant were assessed...
July 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28753571/1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol-ameliorates-arthritic-joints-through-reducing-neutrophil-infiltration-mediated-by-il-6-stat3-and-mip-2-activation
#2
Young-Jun Kim, Jae Min Shin, Su-Hyun Shin, Joo Heon Kim, Ki-Young Sohn, Heung-Jae Kim, Jong-Koo Kang, Sun Young Yoon, Jae Wha Kim
The pathogenesis of rheumatoid arthritis (RA) has been implicated neutrophil extracellular traps (NETs) formation which could generate autoantigen. Neutrophil contributes to initiate and maintain the inflammatory process in the joint. In this study, we show that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) decreases neutrophil migration by regulating the activity of STAT3, a regulator of IL-6 and MIP-2 expression. PLAG caused a decrease in IL-6 production in the RAW264.7 macrophage cell line and in rheumatoid arthritis-fibroblast-like synoviocytes via the regulation of STAT3 signaling without affecting NF-κB signaling...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28665955/pro-fibrotic-compounds-induce-stellate-cell-activation-ecm-remodelling-and-nrf2-activation-in-a-human-3d-multicellular-model-of-liver-fibrosis
#3
Vincenzo Prestigiacomo, Anna Weston, Simon Messner, Franziska Lampart, Laura Suter-Dick
BACKGROUND & AIMS: Currently most liver fibrosis research is performed in vivo, since suitable alternative in vitro systems which are able to recapitulate the cellular events leading to liver fibrosis are lacking. Here we aimed at generating a system containing cells representing the three key players of liver fibrosis (hepatocyte, Kupffer cells and stellate cells) and assess their response to pro-fibrotic compounds such as TGF-β1, methotrexate (MTX) and thioacetamide (TAA). METHODS: Human cell lines representing hepatocytes (HepaRG), Kupffer cell (THP-1 macrophages) and stellate cells (hTERT-HSC) were co-cultured using the InSphero hanging drop technology to generate scaffold-free 3D microtissues, that were treated with pro-fibrotic compounds (TGF-β1, MTX, TAA) for up to 14 days...
2017: PloS One
https://www.readbyqxmd.com/read/28639600/effects-of-polysaccharide-fractions-isolated-from-caltha-palustris-l-on-the-activity-of-phagocytic-cells-humoral-immune-response-in-mice-with-collagen-induced-arthritis-a-comparison-with-methotrexate
#4
Agnieszka Suszko, Bożena Obmińska-Mrukowicz
BACKGROUND & OBJECTIVES: The extracts from Caltha palustris L. have been shown to be beneficial for treating arthritis and rheumatism. In this study, the immunomodulatory effects of polysaccharide fractions B and C of C. palustris extracts were studied, using the collagen-induced arthritis (CIA) mouse arthritis experimental model. The aim was to determine the activity of blood phagocytic cells and humoral immune response in CIA mice treated with polysaccharide fractions from C. palustris...
February 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28598681/soluble-cd206-plasma-levels-in-rheumatoid-arthritis-reflect-decrease-in-disease-activity
#5
Line Dam Heftdal, Kristian Stengaard-Pedersen, Lykke Midtbøll Ørnbjerg, Merete Lund Hetland, Kim Hørslev-Petersen, Peter Junker, Mikkel Østergaard, Malene Hvid, Bent Deleuran, Holger Jon Møller, Stinne Ravn Greisen
Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and infiltration by activated macrophages. TNFα is a central mediator in this process. The mannose receptor, CD206, is a scavenger receptor expressed by M2A-macrophages and dendritic cells. It is involved in collagen internalization and degradation. The soluble form has been suggested as a biomarker of M2A-macrophage activation. The aim of this study was to investigate sCD206 plasma levels in early RA patients initiating anti-TNFα treatment...
June 9, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28569209/in-vivo-monitoring-of-anti-folate-therapy-in-arthritic-rats-using-18-f-fluoro-peg-folate-and-positron-emission-tomography
#6
Durga M S H Chandrupatla, Gerrit Jansen, Ricardo Vos, Mariska Verlaan, Qingshou Chen, Philip S Low, Albert D Windhorst, Adriaan A Lammertsma, Conny J van der Laken, Carla F M Molthoff
BACKGROUND: Folate receptor β (FRβ) is involved in facilitating cellular uptake of folates and anti-folates (such as methotrexate (MTX)). In rheumatoid arthritis, FRβ is expressed on synovial macrophages and recently has been explored as a biomarker for imaging in arthritic rats using the folate-based positron emission tomography (PET) tracer [(18)F]fluoro-PEG-folate. The purpose of this study was to examine whether this folate tracer can also be used to monitor therapeutic efficacy of MTX in arthritic rats...
May 31, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28553113/methotrexate-carried-in-lipid-core-nanoparticles-reduces-myocardial-infarction-size-and-improves-cardiac-function-in-rats
#7
Raul C Maranhão, Maria C Guido, Aline D de Lima, Elaine R Tavares, Alyne F Marques, Marcelo D Tavares de Melo, Jose C Nicolau, Vera Mc Salemi, Roberto Kalil-Filho
PURPOSE: Acute myocardial infarction (MI) is accompanied by myocardial inflammation, fibrosis, and ventricular remodeling that, when excessive or not properly regulated, may lead to heart failure. Previously, lipid core nanoparticles (LDE) used as carriers of the anti-inflammatory drug methotrexate (MTX) produced an 80-fold increase in the cell uptake of MTX. LDE-MTX treatment reduced vessel inflammation and atheromatous lesions induced in rabbits by cholesterol feeding. The aim of the study was to investigate the effects of LDE-MTX on rats with MI, compared with commercial MTX treatment...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28418334/juvenile-idiopathic-arthritis
#8
Kenan Barut, Amra Adrovic, Sezgin Şahin, Özgür Kasapçopur
Juvenile idiopathic arthritis is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. The disease is divided into several subgroups, according to demographic characteristics, clinical features, treatment modalities and disease prognosis. Systemic juvenile idiopathic arthritis, which is one of the most frequent disease subtypes, is characterized by recurrent fever and rash. Oligoarticular juvenile idiopathic arthritis, common among young female patients, is usually accompanied by anti-nuclear antibodie positivity and anterior uveitis...
April 5, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28402587/methotraxate-loaded-hybrid-nanoconstructs-target-vascular-lesions-and-inhibit-atherosclerosis-progression-in-apoe-mice
#9
Cinzia Stigliano, Maricela R Ramirez, Jaykrishna V Singh, Santosh Aryal, Jaehong Key, Elvin Blanco, Paolo Decuzzi
Atherosclerosis is an inflammatory disorder characterized by the progressive thickening of blood vessel walls eventually resulting in acute vascular syndromes. Here, intravenously injectable hybrid nanoconstructs are synthesized for tempering immune cell inflammation locally and systemically. Lipid and polymer chains are nanoprecipitated to form 100 nm spherical polymeric nanoconstructs (SPNs), loaded with methotrexate (MTX) and subsequently labeled with Cu(64) and fluorescent probes for combined nuclear/optical imaging...
April 12, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28399931/pilot-study-comparing-the-childhood-arthritis-rheumatology-research-alliance-carra-systemic-juvenile-idiopathic-arthritis-consensus-treatment-plans
#10
COMPARATIVE STUDY
Yukiko Kimura, Sriharsha Grevich, Timothy Beukelman, Esi Morgan, Peter A Nigrovic, Kelly Mieszkalski, T Brent Graham, Maria Ibarra, Norman Ilowite, Marisa Klein-Gitelman, Karen Onel, Sampath Prahalad, Marilynn Punaro, Sarah Ringold, Dana Toib, Heather Van Mater, Jennifer E Weiss, Pamela F Weiss, Laura E Schanberg
OBJECTIVES: To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry. METHODS: Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC)...
April 11, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/28396011/suppression-of-nfat5-mediated-inflammation-and-chronic-arthritis-by-novel-%C3%AE%C2%BAb-binding-inhibitors
#11
Eun-Jin Han, Hyun Young Kim, Naeun Lee, Nam-Hoon Kim, Seung-Ah Yoo, H Moo Kwon, Dae-Myung Jue, Yune-Jung Park, Chul-Soo Cho, Tran Quang De, Dae Young Jeong, Hee-Jong Lim, Woo Kyu Park, Ge Hyeong Lee, Heeyeong Cho, Wan-Uk Kim
Nuclear factor of activated T cells 5 (NFAT5) has been implicated in the pathogenesis of various human diseases, including cancer and arthritis. However, therapeutic agents inhibiting NFAT5 activity are currently unavailable. To discover NFAT5 inhibitors, a library of >40,000 chemicals was screened for the suppression of nitric oxide, a direct target regulated by NFAT5 activity, through high-throughput screening. We validated the anti-NFAT5 activity of 198 primary hit compounds using an NFAT5-dependent reporter assay and identified the novel NFAT5 suppressor KRN2, 13-(2-fluoro)-benzylberberine, and its derivative KRN5...
April 2017: EBioMedicine
https://www.readbyqxmd.com/read/28391422/osteogenic-sarcoma-systemic-chemotherapy-options-for-localized-disease
#12
REVIEW
Douglas J Harrison, Cindy L Schwartz
Treatment for osteosarcoma, the most common malignant tumor of bone in children and adolescents, has not changed in decades. Treatment is multimodal, employing neoadjuvant chemotherapy followed by aggressive and complete surgical resection to achieve negative margins and a prolonged course of adjuvant chemotherapy. The primary tumor is usually successfully managed via surgery, but micrometastases are likely present in most patients at diagnosis. Death is the result of tumor recurrence in the lungs or more rarely in other bones despite aggressive treatment regimens and is likely attributable to innate resistance to chemotherapy...
April 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28388816/adipose-tissue-macrophages-in-rheumatoid-arthritis-prevalence-disease-related-indicators-and-associations-with-cardiometabolic-risk-factors
#13
Jon T Giles, Antony W Ferrante, Rachel Broderick, Afshin Zartoshti, Janine Rose, Kendall Downer, Hui-Zhu Zhang, Robert J Winchester
Objective Adipose tissue macrophages (ATMs) are a potent source of inflammatory cytokines with profound effects on adipose tissue function, yet their potential role in rheumatoid arthritis (RA) pathobiology is largely unstudied. Methods Periumbilical subcutaneous adipose tissue was obtained from 36 RA patients and 22 non-RA controls frequency matched on demographics and BMI. Samples were stained for the macrophage marker CD68 and the average proportion of ATMs, crown-like structures (CLSs: peri-adipocyte aggregates of three or more ATMs), and fibrosis were compared between groups...
April 7, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28376538/-hepatic-manifestation-of-a-macrophage-activation-syndrome-mas
#14
Michael Nagel, Andreas Schwarting, Beate K Straub, Peter R Galle, Tim Zimmermann
Background Elevated liver values are the most common pathological laboratory result in Germany. Frequent findings, especially in younger patients, are nutritive- or medicamentous- toxic reasons, viral or autoimmune hepatitis. A macrophage activation syndrome (MAS) may manifest like a viral infectious disease with fever, hepatosplenomegaly and pancytopenia and is associated with a high mortality. It is based on an enhanced activation of macrophages with increased cytokine release, leading to organ damage and multi-organ failure...
May 2017: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/28371624/dextran-sulfate-nanoparticles-as-a-theranostic-nanomedicine-for-rheumatoid-arthritis
#15
Roun Heo, Dong Gil You, Wooram Um, Ki Young Choi, Sangmin Jeon, Jong-Sung Park, Yuri Choi, Seunglee Kwon, Kwangmeyung Kim, Ick Chan Kwon, Dong-Gyu Jo, Young Mo Kang, Jae Hyung Park
With the aim of developing nanoparticles for targeted delivery of methotrexate (MTX) to inflamed joints in rheumatoid arthritis (RA), an amphiphilic polysaccharide was synthesized by conjugating 5β-cholanic acid to a dextran sulfate (DS) backbone. Due to its amphiphilic nature, the DS derivative self-assembled into spherical nanoparticles (220 nm in diameter) in aqueous conditions. The MTX was effectively loaded into the DS nanoparticles (loading efficiency: 73.0%) by a simple dialysis method. Interestingly, the DS nanoparticles were selectively taken up by activated macrophages, which are responsible for inflammation and joint destruction, via scavenger receptor class A-mediated endocytosis...
July 2017: Biomaterials
https://www.readbyqxmd.com/read/28347533/influence-of-drugs-carried-in-lipid-nanoparticles-in-coronary-disease-of-rabbit-transplanted-heart
#16
Lucas R Barbieri, Domingos D Lourenço-Filho, Elaine R Tavares, Priscila O Carvalho, Paulo S Gutierrez, Raul C Maranhão, Noedir A G Stolf
BACKGROUND: Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and currently has no effective prevention and treatment. Lipid nanoparticles, termed LDE can carry chemotherapeutic agents in the circulation and concentrates them in the heart. METHODS: Twenty-eight rabbits fed a cholesterol-rich diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg/kg daily) and allocated to four groups of 7 animals treated with intravenous LDE-methotrexate (MTX; 4 mg/kg weekly), with LDE-paclitaxel (PACLI; 4 mg/kg weekly), or with LDE-PACLI (4 mg/kg weekly) and LDE-MTX (4 mg/kg weekly)...
August 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28288894/endogenous-inspired-biomineral-installed-hyaluronan-nanoparticles-as-ph-responsive-carrier-of-methotrexate-for-rheumatoid-arthritis
#17
Md Mahmudul Alam, Hwa Seung Han, Shijin Sung, Jin Hee Kang, Keum Hee Sa, Hasan Al Faruque, Jungwan Hong, Eon Jeong Nam, In San Kim, Jae Hyung Park, Young Mo Kang
Methotrexate (MTX), an anchor drug for rheumatoid arthritis (RA), has been suffered from refractoriness and high toxicity limiting effective dosage. To mitigate these challenges, the ability to selectively deliver MTX to arthritis tissue is a much sought-after modality for the treatment of RA. In this study, we prepared mineralized nanoparticles (MP-HANPs), composed of PEGylated hyaluronic acid (P-HA) as the hydrophilic shell, 5β-cholanic acid as the hydrophobic core, and calcium phosphate (CaP) as the pH-responsive mineral...
March 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28274253/phase-1b-randomized-double-blind-study-of-namilumab-an-anti-granulocyte-macrophage-colony-stimulating-factor-monoclonal-antibody-in-mild-to-moderate-rheumatoid-arthritis
#18
T W J Huizinga, A Batalov, R Stoilov, E Lloyd, T Wagner, D Saurigny, B Souberbielle, E Esfandiari
BACKGROUND: Namilumab (AMG203) is an immunoglobulin G1 monoclonal antibody that binds with high affinity to the GM-CSF ligand. This was a phase 1b, randomized, double-blind study (PRIORA) to assess namilumab in active, mild-to-moderate rheumatoid arthritis (RA). The primary outcome was the safety and tolerability of repeated subcutaneous injections of namilumab in patients with mild-to-moderate RA. METHODS: Adults with mild-to-moderate RA on stable methotrexate doses for ≥12 weeks were eligible...
March 9, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28213566/a-randomised-phase-iib-study-of-mavrilimumab-a-novel-gm-csf-receptor-alpha-monoclonal-antibody-in-the-treatment-of-rheumatoid-arthritis
#19
RANDOMIZED CONTROLLED TRIAL
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...
June 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28204893/gastrointestinal-system-manifestations-in-juvenile-systemic-lupus-erythematosus
#20
Hafize Emine Sönmez, Asuman Nur Karhan, Ezgi Deniz Batu, Yelda Bilginer, Ersin Gümüş, Hülya Demir, Aysel Yüce, Seza Özen
Systemic lupus erythematosus (SLE) is an autoimmune disease which may involve gastrointestinal system (GIS). The aim of this study was to present GIS manifestations of pediatric SLE patients. The medical files of 69 children with SLE followed between January 2011 and January 2016 were reviewed. All fulfilled the Systemic Lupus International Collaborating Clinics criteria. All patients (≤18 years of age) with GIS manifestations were included. GIS manifestations were observed in 19 (27.5%) out of 69 SLE patients and present at the time of SLE diagnosis in 13 (68...
February 16, 2017: Clinical Rheumatology
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