scholarly journals Integrative network analyses of transcriptomics data reveal potential drug targets for acute radiation syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Moore ◽  
Bhanwar Lal Puniya ◽  
Robert Powers ◽  
Chittibabu Guda ◽  
Kenneth W. Bayles ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Drug Repurposing ◽  
Acute Radiation ◽  
Biological Information ◽  
Literature Mining ◽  
Potential Drug ◽  
Long Term Effects ◽  
Acute Radiation Syndrome ◽  
Network Analyses ◽  
Drug Databases

AbstractRecent political unrest has highlighted the importance of understanding the short- and long-term effects of gamma-radiation exposure on human health and survivability. In this regard, effective treatment for acute radiation syndrome (ARS) is a necessity in cases of nuclear disasters. Here, we propose 20 therapeutic targets for ARS identified using a systematic approach that integrates gene coexpression networks obtained under radiation treatment in humans and mice, drug databases, disease-gene association, radiation-induced differential gene expression, and literature mining. By selecting gene targets with existing drugs, we identified potential candidates for drug repurposing. Eight of these genes (BRD4, NFKBIA, CDKN1A, TFPI, MMP9, CBR1, ZAP70, IDH3B) were confirmed through literature to have shown radioprotective effect upon perturbation. This study provided a new perspective for the treatment of ARS using systems-level gene associations integrated with multiple biological information. The identified genes might provide high confidence drug target candidates for potential drug repurposing for ARS.

scholarly journals Author Correction: Integrative network analyses of transcriptomics data reveal potential drug targets for acute radiation syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Moore ◽  
Bhanwar Lal Puniya ◽  
Robert Powers ◽  
Chittibabu Guda ◽  
Kenneth W. Bayles ◽  
...  
Keyword(s):  
Drug Targets ◽  
Acute Radiation ◽  
Potential Drug ◽  
Acute Radiation Syndrome ◽  
Network Analyses ◽  
Transcriptomics Data ◽  
Potential Drug Targets ◽  
Integrative Network

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

2020 ◽  
Author(s):  
Sanaa Bardaweel
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Antimalarial Drug ◽  
Drug Repurposing ◽  
Spike Protein ◽  
Diabetic Patients ◽  
Potential Drug ◽  
Chemokine Production ◽  
Drug Discovery And Development ◽  
Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

scholarly journals Long-Term Hematopoietic Stem Cell Damage in a Murine Model of the Hematopoietic Syndrome of the Acute Radiation Syndrome

2012 ◽  
Vol 103 (4) ◽  
pp. 356-366 ◽  
Author(s):  
Hui Lin Chua ◽  
P. Artur Plett ◽  
Carol H. Sampson ◽  
Mandar Joshi ◽  
Rebeka Tabbey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Murine Model ◽  
Cell Damage ◽  
Acute Radiation ◽  
Hematopoietic Stem ◽  
Acute Radiation Syndrome

The Acute Gastrointestinal Subsyndrome of the Acute Radiation Syndrome

2012 ◽  
Vol 103 (4) ◽  
pp. 411-426 ◽  
Author(s):  
Thomas J. MacVittie ◽  
Ann M. Farese ◽  
Alexander Bennett ◽  
Daniel Gelfond ◽  
Terez Shea-Donohue ◽  
...  
Keyword(s):  
Acute Radiation ◽  
Acute Radiation Syndrome

Acute Radiation Syndrome

BMJ ◽  
1952 ◽  
Vol 2 (4792) ◽  
pp. 1042-1042
Author(s):  
W. M. C. Brown ◽  
L. H. Gray ◽  
R. F. Mahler
Keyword(s):  
Acute Radiation ◽  
Acute Radiation Syndrome

Use of Disproportionality Analysis to Identify Previously Unknown Drug-Associated Causes of Cardiac Arrhythmias Using the Food and Drug Administration Adverse Event Reporting System (FAERS) Database

2021 ◽  
pp. 107424842098408
Author(s):  
Lindsay N. Moreland-Head ◽  
James C. Coons ◽  
Amy L. Seybert ◽  
Matthew P. Gray ◽  
Sandra L. Kane-Gill
Keyword(s):  
Cardiac Arrhythmias ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Potential Drug ◽  
Drug Induced ◽  
Bundle Branch Block ◽  
Search Terms ◽  
Drug Databases ◽  
Safety Consideration

Introduction: Drug-induced QTc-prolongation is a well-known adverse drug reaction (ADR), however there is limited knowledge of other drug-induced arrhythmias. Purpose: The objective of this study is to determine the drugs reported to be associated with arrhythmias other than QTc-prolongation using the FAERS database, possibly identifying potential drug causes that have not been reported previously. Methods: FAERS reports from 2004 quarter 1 through 2019 quarter 1 were combined to create a dataset of approximately 11.6 million reports. Search terms for arrhythmias of interest were selected from the Standardized MedDRA Queries (SMQ) Version 12.0. Frequency of the cardiac arrhythmias were determined for atrial fibrillation, atrioventricular block, bradyarrhythmia, bundle branch block, supraventricular tachycardia, and ventricular fibrillation and linked to the reported causal medications. Reports were further categorized by prior evidence associations using package inserts and established drug databases. A reporting odds ratio (ROR) and confidence interval (CI) were calculated for the ADRs for each drug and each of the 6 cardiac arrhythmias. Results: Of the 11.6 million reports in the FAERS database, 68,989 were specific to cardiac arrhythmias of interest. There were 61 identified medication-reported arrhythmia pairs for the 6 arrhythmia groups with 33 found to have an unknown reported association. Rosiglitazone was the most frequently medication reported across all arrhythmias [ROR 6.02 (CI: 5.82-6.22)]. Other medications with significant findings included: rofecoxib, digoxin, alendronate, lenalidomide, dronedarone, zoledronic acid, adalimumab, dabigatran, and interferon beta-1b. Conclusion: Upon retrospective analysis of the FAERS database, the majority of drug-associated arrhythmias reported were unknown suggesting new potential drug causes. Cardiac arrhythmias other than QTc prolongation are a new area of focus for pharmacovigilance and medication safety. Consideration of future studies should be given to using the FAERS database as a timely pharmacovigilance tool to identify unknown adverse events of medications.

scholarly journals Rescue from lethal acute radiation syndrome (ARS) with severe weight loss by secretome of intramuscularly injected human placental stromal cells

2018 ◽  
Vol 9 (6) ◽  
pp. 1079-1092 ◽  
Author(s):  
Lena Pinzur ◽  
Levent Akyuez ◽  
Lilia Levdansky ◽  
Michal Blumenfeld ◽  
Evgenia Volinsky ◽  
...  
Keyword(s):  
Weight Loss ◽  
Stromal Cells ◽  
Acute Radiation ◽  
Acute Radiation Syndrome ◽  
Severe Weight Loss
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