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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory responses through activation of AMP-activated protein kinase (AMPK) signaling
|
|---|---|
| Published in |
Arthritis Research & Therapy, September 2018
|
| DOI | 10.1186/s13075-018-1699-4 |
| Pubmed ID | |
| Authors |
Charles McWherter, Yun-Jung Choi, Ramon L. Serrano, Sushil K. Mahata, Robert Terkeltaub, Ru Liu-Bryan |
| Abstract |
Arhalofenate acid, the active acid form of arhalofenate, is a non-agonist peroxisome proliferator-activated receptor γ (PPARγ) ligand, with uricosuric activity via URAT1 inhibition. Phase II studies revealed decreased acute arthritis flares in arhalofenate-treated gout compared with allopurinol alone. Hence, we investigated the anti-inflammatory effects and mechanisms of arhalofenate and its active acid form for responses to monosodium urate (MSU) crystals. We assessed in-vivo responses to MSU crystals in murine subcutaneous air pouches and in-vitro responses in murine bone marrow-derived macrophages (BMDMs) by enzyme-linked immunosorbent assay (ELISA), SDS-PAGE/Western blot, immunostaining, and transmission electron microscopy analyses. Oral administration of arhalofenate (250 mg/kg) blunted total leukocyte ingress, neutrophil influx, and air pouch fluid interleukin (IL)-1β, IL-6, and CXCL1 in response to MSU crystal injection (p < 0.05 for each). Arhalofenate acid (100 μM) attenuated MSU crystal-induced IL-1β production in BMDMs via inhibition of NLRP3 inflammasome activation. In addition, arhalofenate acid dose-dependently increased activation (as assessed by phosphorylation) of AMP-activated protein kinase (AMPK). Studying AMPKα1 knockout mice, we elucidated that AMPK mediated the anti-inflammatory effects of arhalofenate acid. Moreover, arhalofenate acid attenuated the capacity of MSU crystals to suppress AMPK activity, regulated expression of multiple downstream AMPK targets that modulate mitochondrial function and oxidative stress, preserved intact mitochondrial cristae and volume density, and promoted anti-inflammatory autophagy flux in BMDMs. Arhalofenate acid is anti-inflammatory and acts via AMPK activation and its downstream signaling in macrophages. These effects likely contribute to a reduction of gout flares. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 20 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 2 | 10% |
| Professor | 2 | 10% |
| Student > Bachelor | 1 | 5% |
| Student > Master | 1 | 5% |
| Student > Ph. D. Student | 1 | 5% |
| Other | 0 | 0% |
| Unknown | 13 | 65% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 15% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
| Computer Science | 1 | 5% |
| Agricultural and Biological Sciences | 1 | 5% |
| Unknown | 14 | 70% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 September 2018.
All research outputs
#3,562,978
of 25,385,509 outputs
Outputs from Arthritis Research & Therapy
#793
of 3,381 outputs
Outputs of similar age
#68,170
of 345,662 outputs
Outputs of similar age from Arthritis Research & Therapy
#26
of 67 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,381 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one has done well, scoring higher than 75% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 345,662 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 67 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 56% of its contemporaries.