Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiologic studies have demonstrated that increased high-density lipoprotein cholesterol (HDL-C) is a protective factor against cardiovascular disease. However, the beneficial therapeutic effects of raising HDL-C are proving difficult to confirm in humans. Macrophage-specific reverse cholesterol transport (RCT) is thought to be one of the most important HDL-mediated cardioprotective mechanisms. A new approach was developed to measure in vivo RCT from labeled cholesterol macrophages to liver and feces in mice. Since its original publication, this method has been extensively used to assess the effects of genetic manipulation of pivotal genes involved in HDL metabolism on this major HDL antiatherogenic function in mice. These studies indicate that in vivo macrophage-specific RTC is a strong predictor of atherosclerosis susceptibility compared with steady-state plasma HDL-C levels or other global RCT measurements. This review aims to identify the best molecular targets for improving this HDL antiatherogenic function. Strong evidence supports a positive effect of interventions on macrophage adenosine triphosphate-binding cassette transporter (ABC) A1 and neutral cholesteryl ester hydrolase, apolipoprotein (apo) A-I, apoE, liver scavenger receptor class B type I and ABCG5/G8 on in vivo macrophage-specific RCT and atherosclerosis susceptibility. However, other genetic modifications have yielded conflicting results. Several preclinical studies tested the effects on macrophage-specific RCT in vivo of promising new HDL-based therapeutic agents, which include cholesteryl ester transfer protein inhibitors, apoA-I-directed therapies, liver X receptor and peroxisome proliferator-activated receptor agonists, intestinal cholesterol absorption inhibitors, fish oil and phenolic acid intake, inflammatory modulation and non-nucleoside reverse transcriptase inhibitors. This review also discusses recent findings on the potential effects of these therapeutic approaches on macrophage RCT in mice and cardiovascular risk in humans.
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PMID:Seeking novel targets for improving in vivo macrophage-specific reverse cholesterol transport: translating basic science into new therapies for the prevention and treatment of atherosclerosis. 2114 75

Hepatitis E virus (HEV) is a common cause of acute on chronic liver failure (ACLF) in HEV hyperendemic regions with high mortality. Treatment for HEV-induced ACLF is currently not available. Recently, efficacy of ribavirin in genotype 3 chronic hepatitis E patients has been reported; however, whether ribavirin is effective in genotype 1 HEV infection is not yet known. The present study includes four patients with HEV-induced ACLF treated with ribavirin in a genotype 1 HEV hyperendemic region. Diagnosis of ACLF was made by conventional criteria and HEV as the cause of ACLF was confirmed by detection of HEV RNA by reverse transcriptase PCR. Ribavirin dose ranged from 200 to 600 mg/day and was used for a median duration of 12 (range 3-24) weeks. All patients had undetectable HEV in 3-8 weeks, survived and none had serious adverse effects. This preliminary observation from a single centre indicates that ribavirin may be an effective therapeutic agent for HEV-induced ACLF and a randomized control trial is needed to establish its efficacy.
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PMID:Ribavirin therapy for hepatitis E virus-induced acute on chronic liver failure: a preliminary report. 2291 May 32

Macrophages are natural target cells of human immunodeficiency virus type 1 (HIV-1). Viral replication appears to be delayed in these cells compared to lymphocytes; however, little is known about the kinetics of early post-entry events. Time-of-addition experiments using several HIV-1 inhibitors and the detection of reverse transcriptase (RT) products with droplet digital PCR (ddPCR) revealed that early replication was delayed in primary human monocyte-derived macrophages of several donors and peaked late after infection. Direct imaging of reverse-transcription and pre-integration complexes (RTC/PIC) by click-labeling of newly synthesized DNA further confirmed our findings and showed a concomitant shift to the nuclear stage over time. Altering the entry pathway enhanced infectivity but did not affect kinetics of viral replication. The addition of viral protein X (Vpx) enhanced productive infection and accelerated completion of reverse transcription and nuclear entry. We propose that sterile alpha motif (SAM) and histidine/aspartate (HD) domain-containing protein 1 (SAMHD1) activity lowering deoxyribonucleotide triphosphate (dNTP) pools is the principal factor delaying early HIV-1 replication in macrophages.
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PMID:Detailed Characterization of Early HIV-1 Replication Dynamics in Primary Human Macrophages. 3042 2


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