Evidence map›Paper›PMID 34171382›Full record

ArticleLife sciences2021

Zinc supplementation augments the suppressive effects of repurposed NF-κB inhibitors on ACE2 expression in human lung cell lines.

Ming-Cheng Lee, Yin-Kai Chen, Jyy-Jih Tsai-Wu, Yih-Jen Hsu, Bor-Ru Lin

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Life sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Review
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  4. Article
  5. Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022
    Review
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  7. Cytokines and microRNAs in SARS-CoV-2: What do we know?Molecular therapy. Nucleic acids · 2022
    Review
  8. Article
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  10. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Ming-Cheng LeeDepartment of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei 10051, Taiwan, ROC.
Yin-Kai ChenGraduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan, ROC; Department of Hematology, National Taiwan University Cancer Center, Taipei 10672, Taiwan, ROC.
Jyy-Jih Tsai-WuDepartment of Medical Research, National Taiwan University Hospital, Taipei 10051, Taiwan, ROC.
Yih-Jen HsuDepartment of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei 10051, Taiwan, ROC.
Bor-Ru LinDepartment of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei 10051, Taiwan, ROC; Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei 10051, Taiwan, ROC. Electronic address: brucelin@ntuh.gov.tw.
National Taiwan University Hospital · TWNational Taiwan University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsAngiotensin-converting enzyme 2 (ACE2) is a key negative regulator of the renin-angiotensin system and also a major receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we reveal a role for NF-κB in human lung cell expression of ACE2, and we further explore the potential utility of repurposing NF-κB inhibitors to downregulate ACE2. MAIN

methodsExpression of ACE2 was assessed by Western blotting and RT-qPCR in multiple human lung cell lines with or without NF-κB inhibitor treatment. Surface ACE2 expression and intracellular reactive oxygen species (ROS) levels were measured with flow cytometry. p50 was knocked down with siRNA. Cytotoxicity was monitored by PARP cleavage and MTS assay. KEY

findingsPyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, suppressed endogenous ACE2 mRNA and protein expression in H322M and Calu-3 cells. The ROS level in H322M cells was increased after PDTC treatment, and pretreatment with N-acetyl-cysteine (NAC) reversed PDTC-induced ACE2 suppression. Meanwhile, treatment with hydrogen peroxide augmented ACE2 suppression in H322M cells with p50 knockdown. Two repurposed NF-κB inhibitors, the anthelmintic drug triclabendazole and the antiprotozoal drug emetine, also reduced ACE2 mRNA and protein levels. Moreover, zinc supplementation augmented the suppressive effects of triclabendazole and emetine on ACE2 expression in H322M and Calu-3 cells. SIGNIFICANCE: These results suggest that ACE2 expression is modulated by ROS and NF-κB signaling in human lung cells, and the combination of zinc with triclabendazole or emetine shows promise for clinical treatment of ACE2-related disease.

Indexed as

Angiotensin-Converting Enzyme 2Antiparasitic AgentsCell LineCOVID-19COVID-19 Drug TreatmentDown-RegulationDrug RepositioningEmetineHumansLungNF-kappa BPyrrolidinesThiocarbamatesTriclabendazoleZincACE2 protein, humanAngiotensin-Converting Enzyme 2Antiparasitic AgentsEmetineNF-kappa Bpyrrolidine dithiocarbamic acidPyrrolidinesThiocarbamatesTriclabendazoleZincACE2EmetineNF-kappa BROSTriclabendazoleZinc

Identifiers

PMID34171382
PMCPMC8219909
OpenAlexW3177134013

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.