scholarly journals “Amantadine disrupts lysosomal gene expression; potential therapy for COVID19”

2020 ◽  
Author(s):  
Sandra P. Smieszek ◽  
Bart P Przychodzen ◽  
Mihael H Polymeropoulos
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Cathepsin L ◽  
Drug Screen ◽  
Direct Inhibition ◽  
The Us ◽  
Lysosomotropic Agent ◽  
A Cell ◽  
Expression Potential ◽  
Lysosomal Gene

AbstractSARS-coronavirus 2 is the causal agent of the COVID-19 outbreak. SARS-Cov-2 entry into a cell is dependent upon binding of the viral spike (S) protein to cellular receptor and on cleavage of the spike protein by the host cell proteases such as Cathepsin L and Cathepsin B. CTSL/B are crucial elements of lysosomal pathway and both enzymes are almost exclusively located in the lysosomes.CTSL disruption offers potential for CoVID-19 therapies. The mechanisms of disruption include: decreasing expression of CTSL, direct inhibition of CTSL activity and affecting the conditions of CTSL environment (increase pH in lysosomes).We have conducted a high throughput drug screen gene expression analysis to identify compounds that would downregulate the expression of CTSL/CTSB. One of the top significant results shown to downregulate the expression of the CTSL gene is Amantadine. Amantadine was approved by the US Food and Drug Administration in 1968 as a prophylactic agent for influenza and later for Parkinson’s disease. It is available as a generic drug..Amantadine in addition to downregulating CTSL appears to further disrupt lysosomal pathway, hence interfering with the capacity of the virus to replicate. It acts as a lysosomotropic agent altering the CTSL functional environment. We hypothesize that Amantadine could decrease the viral load in SARS-CoV-2 positive patients and as such it may serve as a potent therapeutic decreasing the replication and infectivity of the virus likely leading to better clinical outcomes. Clinical studies will be needed to examine the therapeutic utility of amantadine in COVID-19 infection.

scholarly journals Identification of Pueraria spp. through DNA barcoding and comparative transcriptomics

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Laci M. Adolfo ◽  
Xiaolan Rao ◽  
Richard A. Dixon
Keyword(s):  
Gene Expression ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Internal Transcribed Spacer ◽  
Gene Expression Analysis ◽  
Population Diversity ◽  
Economic Damage ◽  
Differential Analysis ◽  
The Us ◽  
Noxious Weed

Abstract Background Kudzu is a term used generically to describe members of the genus Pueraria. Kudzu roots have been used for centuries in traditional Chinese medicine in view of their high levels of beneficial isoflavones including the unique 8-C-glycoside of daidzein, puerarin. In the US, kudzu is seen as a noxious weed causing ecological and economic damage. However, not all kudzu species make puerarin or are equally invasive. Kudzu remains difficult to identify due to its diverse morphology and inconsistent nomenclature. Results We have generated sequences for the internal transcribed spacer 2 (ITS2) and maturase K (matK) regions of Pueraria montana lobata, P. montana montana, and P. phaseoloides, and identified two accessions previously used for differential analysis of puerarin biosynthesis as P. lobata and P. phaseoloides. Additionally, we have generated root transcriptomes for the puerarin-producing P. m. lobata and the non-puerarin producing P. phaseoloides. Within the transcriptomes, microsatellites were identified to aid in species identification as well as population diversity. Conclusions The barcode sequences generated will aid in fast and efficient identification of the three kudzu species. Additionally, the microsatellites identified from the transcriptomes will aid in genetic analysis. The root transcriptomes also provide a molecular toolkit for comparative gene expression analysis towards elucidation of the biosynthesis of kudzu phytochemicals.

scholarly journals Gene Expression Analysis of PTEN Positive Glioblastoma Stem Cells Identifies DUB3 and Wee1 Modulation in a Cell Differentiation Model

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e81432 ◽  
Author(s):  
Stefano Forte ◽  
Alfredo Pagliuca ◽  
Eugenia T. Maniscalchi ◽  
Rosario Gulino ◽  
Giovanna Calabrese ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cell Differentiation ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Glioblastoma Stem Cells ◽  
A Cell ◽  
Differentiation Model ◽  
Cell Differentiation Model

Nutrient-regulated gene expression in eukaryotes

2006 ◽  
Vol 73 ◽  
pp. 85-96 ◽  
Author(s):  
Richard J. Reece ◽  
Laila Beynon ◽  
Stacey Holden ◽  
Amanda D. Hughes ◽  
Karine Rébora ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Control ◽  
Direct Interaction ◽  
Signalling Pathways ◽  
A Cell ◽  
One Step ◽  
Higher Eukaryotes ◽  
Regulated Gene Expression

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.

Gene expression analysis of metabolic markers during bone regeneration in a rat model

2014 ◽  
Vol 23 (03) ◽  
pp. 207-211
Author(s):  
C. Kasch ◽  
A. Osterberg ◽  
Thordis Granitzka ◽  
T. Lindner ◽  
M. Haenle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Saline Solution ◽  
Female Rats ◽  
Synthesis Rate ◽  
Metabolic Markers ◽  
Expression Levels ◽  
Fibrotic Tissue ◽  
Intermittent Pth ◽  
Lower Expression

SummaryThe RANK/RANKL/OPG system plays an important role in the regulation of bone metabolism and bony integration around implants. The aim of this study was to analyse gene expression of OPG, RANK, and RANKL in regenerating bone during implant integration. Additionally, the effect of intermittent para - thyroid hormone (PTH) treatment was analysed. A titanium chamber was implanted in the proximal tibiae of 48 female rats. The animals received either human PTH or saline solution (NaCl). After 21 and 42 days, RNA was isolated from tissue adjacent to the implant and expression of RANK, RANKL, and OPG was analysed. After 21 days, very low expression levels of all genes were shown. In contrast, increased gene expression after 42 days was determined. Expression of RANK and RANKL was lower than that for OPG. The lower expression levels after 21 days might be due to still ossifying, fibrotic tissue around the titanium chamber. An increased OPG synthesis rate associated with decreased RANKL expression after 42 days revealed bone-forming processes. Despite significant differences in gene expression between the time points, only slight differences were observed between application of intermittent PTH and NaCl after a period of 42 days.

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