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X Demographics
Mendeley readers
Attention Score in Context
| Title |
N,N-Dimethyl-3β-hydroxycholenamide Reduces Retinal Cholesterol via Partial Inhibition of Retinal Cholesterol Biosynthesis Rather Than its Liver X Receptor Transcriptional Activity
|
|---|---|
| Published in |
Frontiers in Pharmacology, July 2018
|
| DOI | 10.3389/fphar.2018.00827 |
| Pubmed ID | |
| Authors |
Nicole El-Darzi, Artem Astafev, Natalia Mast, Aicha Saadane, Morrie Lam, Irina A. Pikuleva |
| Abstract |
N,N-dimethyl-3β-hydroxycholenamide (DMHCA) is an experimental pharmaceutical and a steroidal liver X receptor (LXR) agonist, which does not induce undesired hepatic lipogenesis. Herein, DMHCA was evaluated for its retinal effects on normal C57BL/6J and Cyp27a1-/-Cyp46a1-/- mice; the latter having higher retinal total and esterified cholesterol in addition to retinal vascular abnormalities. Different doses and two formulations were used for DMHCA delivery either via drinking water (C57BL/6J mice) or by oral gavage (Cyp27a1-/-Cyp46a1-/- mice). The duration of treatment was 1 week for C57BL/6J mice and 2 or 4 weeks for Cyp27a1-/-Cyp46a1-/- mice. In both genotypes, the higher DMHCA doses (37-80 mg/kg of body weight/day) neither increased serum triglycerides nor serum cholesterol but altered the levels of retinal sterols. Total retinal cholesterol was decreased in the DMHCA-treated mice, mainly due to a decrease in retinal unesterified cholesterol. In addition, retinal levels of cholesterol precursors lanosterol, zymosterol, desmosterol, and lathosterol were changed in Cyp27a1-/-Cyp46a1-/- mice. In both genotypes, DMHCA effect on retinal expression of the LXR target genes was only moderate and gender-specific. Collectively, the data obtained provide evidence for a decrease in retinal cholesterol as a result of DMHCA acting in the retina as an enzyme inhibitor of cholesterol biosynthesis rather than a LXR transcriptional activator. Specifically, DMHCA appears to partially inhibit the cholesterol biosynthetic enzyme Δ24-dehydrocholesterol reductase rather than upregulate the expression of LXR target genes involved in reverse cholesterol transport. The identified DMHCA dosages, formulations, and routes of delivery as well as the observed effects on the retina should be considered in future studies using DMHCA as a potential therapeutic for age-related macular degeneration and diabetic retinopathy. |
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 17 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 24% |
| Student > Ph. D. Student | 3 | 18% |
| Student > Doctoral Student | 2 | 12% |
| Student > Master | 2 | 12% |
| Other | 1 | 6% |
| Other | 2 | 12% |
| Unknown | 3 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 24% |
| Medicine and Dentistry | 3 | 18% |
| Neuroscience | 2 | 12% |
| Immunology and Microbiology | 1 | 6% |
| Biochemistry, Genetics and Molecular Biology | 1 | 6% |
| Other | 0 | 0% |
| Unknown | 6 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 August 2018.
All research outputs
#20,529,980
of 23,099,576 outputs
Outputs from Frontiers in Pharmacology
#10,326
of 16,458 outputs
Outputs of similar age
#288,660
of 330,304 outputs
Outputs of similar age from Frontiers in Pharmacology
#275
of 398 outputs
Altmetric has tracked 23,099,576 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,458 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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 330,304 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 398 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.